期刊论文

【摘要】

Background

Mitochondrial dysfunction and defects in oxidative metabolism are a characteristic feature of many chronic illnesses not currently classified as mitochondrial diseases. Examples of such illnesses include bipolar disorder, multiple sclerosis, Parkinson’s disease, schizophrenia, depression, autism, and chronic fatigue syndrome.

Discussion

While the majority of patients with multiple sclerosis appear to have widespread mitochondrial dysfunction and impaired ATP production, the findings in patients diagnosed with Parkinson’s disease, autism, depression, bipolar disorder schizophrenia and chronic fatigue syndrome are less consistent, likely reflecting the fact that these diagnoses do not represent a disease with a unitary pathogenesis and pathophysiology. However, investigations have revealed the presence of chronic oxidative stress to be an almost invariant finding in study cohorts of patients afforded each diagnosis. This state is characterized by elevated reactive oxygen and nitrogen species and/or reduced levels of glutathione, and goes hand in hand with chronic systemic inflammation with elevated levels of pro-inflammatory cytokines.

Summary

This paper details mechanisms by which elevated levels of reactive oxygen and nitrogen species together with elevated pro-inflammatory cytokines could conspire to pave a major road to the development of mitochondrial dysfunction and impaired oxidative metabolism seen in many patients diagnosed with these disorders.

【授权许可】

2015 Berk and Morris; licensee BioMed Central.

【预览】

附件列表
Files	Size	Format	View
20150411023138804.pdf	1000KB	PDF	download
Figure 2.	29KB	Image	download
Figure 1.	37KB	Image	download

【图表】

Figure 1.

Figure 2.

【参考文献】

[1]Morris G, Maes M: Mitochondrial dysfunctions in myalgic encephalomyelitis/chronic fatigue syndrome explained by activated immuno-inflammatory, oxidative and nitrosative stress pathways. Metab Brain Dis. 2014, 29:19-36.
[2]Guo T, Chen H, Liu B, Ji W, Yang C: Methylenetetrahydrofolate reductase polymorphisms C677T and risk of autism in the Chinese Han population. Genet Test Mol Biomarkers. 2012, 16:968-73.
[3]Pagano G, Castello G, Pallardó FV: Sjøgren’s syndrome-associated oxidative stress and mitochondrial dysfunction: prospects for chemoprevention trials. Free Radic Res. 2013, 47:71-3.
[4]López-Erauskin J, Galino J, Bianchi P, Fourcade S, Andreu AL, Ferrer I, et al.: Oxidative stress modulates mitochondrial failure and cyclophilin D function in X-linked adrenoleukodystrophy. Brain. 2012, 135:3584-98.
[5]Perl A, Hanczko R, Doherty E: Assessment of mitochondrial dysfunction in lymphocytes of patients with systemic lupus erythematosus. Methods Mol Biol. 2012, 900:61-89.
[6]Morris G, Maes M: Myalgic encephalomyelitis/chronic fatigue syndrome and encephalomyelitis disseminata/multiple sclerosis show remarkable levels of similarity in phenomenology and neuroimmune characteristics. BMC Med. 2013, 11:205.
[7]Ciccone S, Maiani E, Bellusci G, Diederich M, Gonfloni S: Parkinson’s disease: a complex interplay of mitochondrial DNA alterations and oxidative stress. Int J Mol Sci. 2013, 14:2388-409.
[8]Rossignol DA, Frye RE: Evidence linking oxidative stress, mitochondrial dysfunction, and inflammation in the brain of individuals with autism. Front Physiol. 2014, 5:150.
[9]Tasset I, Agüera E, Sánchez-López F, Feijóo M, Giraldo AI, Cruz AH, et al.: Peripheral oxidative stress in relapsing-remitting multiple sclerosis. Clin Biochem. 2012, 45:440-4.
[10]Nikić I, Merkler D, Sorbara C, Brinkoetter M, Kreutzfeldt M, Bareyre FM, et al.: A reversible form of axon damage in experimental autoimmune encephalomyelitis and multiple sclerosis. Nat Med. 2011, 17:495-9.
[11]Oliveira SR, Kallaur AP, Simão AN, Morimoto HK, Lopes J, Panis C, et al.: Oxidative stress in multiple sclerosis patients in clinical remission: association with the expanded disability status scale. J Neurol Sci. 2012, 321:49-53.
[12]Kalman B, Laitinen K, Komoly S: The involvement of mitochondria in the pathogenesis of multiple sclerosis. J Neuroimmunol. 2007, 188:1-12.
[13]Song Y, Pinniger GJ, Bakker AJ, Moss TJ, Noble PB, Berry CA, et al.: Lipopolysaccharide-induced weakness in the preterm diaphragm is associated with mitochondrial electron transport chain dysfunction and oxidative stress. PLoS One. 2013, 8:e73457.
[14]Rose S, Frye RE, Slattery J, Wynne R, Tippett M, Pavliv O, et al.: Oxidative stress induces mitochondrial dysfunction in a subset of autism lymphoblastoid cell lines in a well-matched case control cohort. PLoS One. 2014, 9:e85436.
[15]Galley HF: Bench-to-bedside review: targeting antioxidants to mitochondria in sepsis. Crit Care. 2010, 14:230.
[16]Galley HF: Oxidative stress and mitochondrial dysfunction in sepsis. Br J Anaesth. 2011, 107:57-64.
[17]Morris G, Anderson G, Dean O, Berk M, Galecki P, Martin-Subero M, et al.: The glutathione system: a new drug target in neuroimmune disorders. Mol Neurobiol 2014, 50:1059-84.
[18]Fischer MT, Sharma R, Lim JL, Haider L, Frischer JM, Drexhage J, et al.: NADPH oxidase expression in active multiple sclerosis lesions in relation to oxidative tissue damage and mitochondrial injury. Brain. 2012, 135:886-99.
[19]Gilgun-Sherki Y, Melamed E, Offen D: The role of oxidative stress in the pathogenesis of multiple sclerosis: the need for effective antioxidant therapy. J Neurol. 2004, 251:261-8.
[20]Poyton RO, Ball KA, Castello PR: Mitochondrial generation of free radicals and hypoxic signaling. Trends Endocrinol Metab. 2009, 20:332-40.
[21]Surace MJ, Block ML: Targeting microglia-mediated neurotoxicity: the potential of NOX2 inhibitors. Cell Mol Life Sci. 2012, 69:2409-27.
[22]Leto TL, Geiszt M: Role of Nox family NADPH oxidases in host defense. Antioxid Redox Signal. 2006, 8:1549-61.
[23]Honorat JA, Kinoshita M, Okuno T, Takata K, Koda T, Tada S, et al.: Xanthine oxidase mediates axonal and myelin loss in a murine model of multiple sclerosis. PLoS One. 2013, 8:e71329.
[24]Prolo C, Alvarez MN, Radi R: Peroxynitrite, a potent macrophage-derived oxidizing cytotoxin to combat invading pathogens. Biofactors. 2014, 40:215-25.
[25]Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB: Oxidative stress, inflammation, and cancer: how are they linked? Free Radic Biol Med. 2010, 49:1603-16.
[26]Vaziri ND: Causal link between oxidative stress, inflammation, and hypertension. Iran J Kidney Dis. 2008, 2:1-10.
[27]Alvarez MN, Peluffo G, Piacenza L, Radi R: Intraphagosomal peroxynitrite as a macrophage-derived cytotoxin against internalized Trypanosoma cruzi: consequences for oxidative killing and role of microbial peroxiredoxins in infectivity. J Biol Chem. 2011, 286:6627-40.
[28]Khansari N, Shakiba Y, Mahmoudi M: Chronic inflammation and oxidative stress as a major cause of age-related diseases and cancer. Recent Pat Inflamm Allergy Drug Discov. 2009, 3:73-80.
[29]Ortiz GG, Pacheco-Moisés FP, Bitzer-Quintero OK, Ramírez-Anguiano AC, Flores-Alvarado LJ, Ramírez-Ramírez V, et al.: Immunology and oxidative stress in multiple sclerosis: clinical and basic approach. Clin Dev Immunol. 2013, 2013:708659.
[30]Lucas K, Maes M: Role of the Toll Like receptor (TLR) radical cycle in chronic inflammation: possible treatments targeting the TLR4 pathway. Mol Neurobiol. 2013, 48:190-204.
[31]Hwang O: Role of oxidative stress in Parkinson’s disease. Exp Neurobiol. 2013, 22:11-7.
[32]Witherick J, Wilkins A, Scolding N, Kemp K: Mechanisms of oxidative damage in multiple sclerosis and a cell therapy approach to treatment. Autoimmune Dis. 2010, 2011:164608.
[33]Perry VH, Holmes C: Microglial priming in neurodegenerative disease. Nat Rev Neurol. 2014, 10:217-24.
[34]Cunningham C: Microglia and neurodegeneration: the role of systemic inflammation. Glia. 2013, 61:71-90.
[35]Steel C, Breving K, Tavakoli S, Kim W, Sanford L, Ciavarra R. Role of peripheral immune response in microglia activation and regulation of brain chemokine and proinflammatory cytokine responses induced during VSV encephalitis. Journal Of Neuroimmunology. 2014;267(1-2):50–60. doi:10.1016/j.jneuroim.2013.12.002.
[36]Morris G, Maes M: Oxidative and nitrosative stress and immune-inflammatory pathways in patients with myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS). Curr Neuropharmacol. 2014, 12:168-85.
[37]Morris G, Maes M: A neuro-immune model of myalgic encephalomyelitis/chronic fatigue syndrome. Metab Brain Dis. 2013, 28:523-40.
[38]Su X, Federoff HJ: Immune responses in Parkinson’s disease: interplay between central and peripheral immune systems. Biomed Res Int. 2014, 2014:275178.
[39]Ferrari CC, Tarelli R: Parkinson’s disease and systemic inflammation. Parkinsons Dis. 2011, 2011:436813.
[40]Lunnon K, Teeling JL, Tutt AL, Cragg MS, Glennie MJ, Perry VH: Systemic inflammation modulates Fc receptor expression on microglia during chronic neurodegeneration. J Immunol. 2011, 186:7215-24.
[41]Perry VH: Contribution of systemic inflammation to chronic neurodegeneration. Acta Neuropathol. 2010, 120:277-86.
[42]Agostinho P, Cunha RA, Oliveira C: Neuroinflammation, oxidative stress and the pathogenesis of Alzheimer’s disease. Curr Pharm Des. 2010, 16:2766-78.
[43]Reale M, Iarlori C, Thomas A, Gambi D, Perfetti B, Di Nicola M, et al.: Peripheral cytokines profile in Parkinson’s disease. Brain Behav Immun. 2009, 23:55-63.
[44]Reale M, Greig NH, Kamal MA: Peripheral chemo-cytokine profiles in Alzheimer’s and Parkinson’s diseases. Mini Rev Med Chem. 2009, 9:1229-41.
[45]Mosley RL, Hutter-Saunders JA, Stone DK, Gendelman HE: Inflammation and adaptive immunity in Parkinson’s disease. Cold Spring Harb Perspect Med. 2012, 2:a009381.
[46]Nakamura M, Matsuoka T, Chihara N, Miyake S, Sato W, Araki M, et al.: Differential effects of fingolimod on B-cell populations in multiple sclerosis. Mult Scler 2014, 20:1371-80.
[47]Hauser SL, Waubant E, Arnold DL, Vollmer T, Antel J, Fox RJ, et al.: B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N Engl J Med. 2008, 358:676-88.
[48]Polman CH, O’Connor PW, Havrdova E, Hutchinson M, Kappos L, Miller DH, et al.: A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med. 2006, 354:899-910.
[49]Romme Christensen J, Börnsen L, Hesse D, Krakauer M, Sørensen PS, Søndergaard HB, et al.: Cellular sources of dysregulated cytokines in relapsing-remitting multiple sclerosis. J Neuroinflammation. 2012, 9:215.
[50]Beck J, Rondot P, Catinot L, Falcoff E, Kirchner H, Wietzerbin J: Increased production of interferon gamma and tumor necrosis factor precedes clinical manifestation in multiple sclerosis: do cytokines trigger off exacerbations. Acta Neurol Scand. 1988, 78:318-23.
[51]Maimone D, Gregory S, Arnason BG, Reder AT: Cytokine levels in the cerebrospinal fluid and serum of patients with multiple sclerosis. J Neuroimmunol. 1991, 32:67-74.
[52]Navikas V, Link H: Review: cytokines and the pathogenesis of multiple sclerosis. J Neurosci Res. 1996, 45:322-33.
[53]Martins TB, Rose JW, Jaskowski TD, Wilson AR, Husebye D, Seraj HS, et al.: Analysis of proinflammatory and anti-inflammatory cytokine serum concentrations in patients with multiple sclerosis by using a multiplexed immunoassay. Am J Clin Pathol. 2011, 136:696-704.
[54]Gold SM, Krüger S, Ziegler KJ, Krieger T, Schulz KH, Otte C, et al.: Endocrine and immune substrates of depressive symptoms and fatigue in multiple sclerosis patients with comorbid major depression. J Neurol Neurosurg Psychiatry. 2011, 82:814-8.
[55]Heesen C, Nawrath L, Reich C, Bauer N, Schulz KH, Gold SM: Fatigue in multiple sclerosis: an example of cytokine mediated sickness behaviour? J Neurol Neurosurg Psychiatry. 2006, 77:34-9.
[56]Flachenecker P, Bihler I, Weber F, Gottschalk M, Toyka KV, Rieckmann P: Cytokine mRNA expression in patients with multiple sclerosis and fatigue. Mult Scler. 2004, 10:165-9.
[57]Disanto G, Berlanga AJ, Handel AE, Para AE, Burrell AM, Fries A, et al.: Heterogeneity in multiple sclerosis: scratching the surface of a complex disease. Autoimmune Dis. 2010, 2011:932351.
[58]Lucchinetti CF, Brück W, Rodriguez M, Lassmann H: Distinct patterns of multiple sclerosis pathology indicates heterogeneity on pathogenesis. Brain Pathol. 1996, 6:259-74.
[59]Gironi M, Borgiani B, Mariani E, Cursano C, Mendozzi L, Cavarretta R, et al.: Oxidative stress is differentially present in multiple sclerosis courses, early evident, and unrelated to treatment. J Immunol Res. 2014, 2014:961863.
[60]Miller E, Walczak A, Saluk J, Ponczek MB, Majsterek I: Oxidative modification of patient’s plasma proteins and its role in pathogenesis of multiple sclerosis. Clin Biochem. 2012, 45:26-30.
[61]Gonsette RE: Neurodegeneration in multiple sclerosis: the role of oxidative stress and excitotoxicity. J Neurol Sci. 2008, 274:48-53.
[62]Stavropoulou C, Zachaki S, Alexoudi A, Chatzi I, Georgakakos VN, Terzoudi GI, et al.: The C609T inborn polymorphism in NAD(P)H:quinone oxidoreductase 1 is associated with susceptibility to multiple sclerosis and affects the risk of development of the primary progressive form of the disease. Free Radic Biol Med. 2011, 51:713-8.
[63]Bizzozero OA, DeJesus G, Callahan K, Pastuszyn A: Elevated protein carbonylation in the brain white matter and gray matter of patients with multiple sclerosis. J Neurosci Res. 2005, 81:687-95.
[64]Greco A, Minghetti L, Sette G, Fieschi C, Levi G: Cerebrospinal fluid isoprostane shows oxidative stress in patients with multiple sclerosis. Neurology. 1999, 53:1876-9.
[65]Toshniwal PK, Zarling EJ: Evidence for increased lipid peroxidation in multiple sclerosis. Neurochem Res. 1992, 17:205-7.
[66]Calabrese V, Scapagnini G, Ravagna A, Bella R, Foresti R, Bates TE, et al.: Nitric oxide synthase is present in the cerebrospinal fluid of patients with active multiple sclerosis and is associated with increases in cerebrospinal fluid protein nitrotyrosine and S-nitrosothiols and with changes in glutathione levels. J Neurosci Res. 2002, 70:580-7.
[67]Mattsson N, Haghighi S, Andersen O, Yao Y, Rosengren L, Blennow K, et al.: Elevated cerebrospinal fluid F2-isoprostane levels indicating oxidative stress in healthy siblings of multiple sclerosis patients. Neurosci Lett. 2007, 414:233-6.
[68]Jack C, Antel J, Brück W, Kuhlmann T: Contrasting potential of nitric oxide and peroxynitrite to mediate oligodendrocyte injury in multiple sclerosis. Glia. 2007, 55:926-34.
[69]Bagasra O, Michaels FH, Zheng YM, Bobroski LE, Spitsin SV, Fu ZF, et al.: Activation of the inducible form of nitric oxide synthase in the brains of patients with multiple sclerosis. Proc Natl Acad Sci U S A. 1995, 92:12041-5.
[70]Giovannoni G, Heales SJ, Land JM, Thompson EJ: The potential role of nitric oxide in multiple sclerosis. Mult Scler. 1998, 4:212-6.
[71]Tasset I, Bahamonde C, Agüera E, Conde C, Cruz AH, Pérez-Herrera A, et al.: Effect of natalizumab on oxidative damage biomarkers in relapsing-remitting multiple sclerosis. Pharmacol Rep. 2013, 65:624-31.
[72]Fiorini A, Koudriavtseva T, Bucaj E, Coccia R, Foppoli C, Giorgi A, et al.: Involvement of oxidative stress in occurrence of relapses in multiple sclerosis: the spectrum of oxidatively modified serum proteins detected by proteomics and redox proteomics analysis. PLoS One. 2013, 8:e65184.
[73]Rejdak K, Petzold A, Stelmasiak Z, Giovannoni G: Cerebrospinal fluid brain specific proteins in relation to nitric oxide metabolites during relapse of multiple sclerosis. Mult Scler. 2008, 14:59-66.
[74]Centonze D, Muzio L, Rossi S, Cavasinni F, De Chiara V, Bergami A, et al.: Inflammation triggers synaptic alteration and degeneration in experimental autoimmune encephalomyelitis. J Neurosci. 2009, 29:3442-52.
[75]Campbell GR, Mahad DJ: Clonal expansion of mitochondrial DNA deletions and the progression of multiple sclerosis. CNS Neurol Disord Drug Targets. 2012, 11:589-97.
[76]Centonze D, Muzio L, Rossi S, Furlan R, Bernardi G, Martino G: The link between inflammation, synaptic transmission and neurodegeneration in multiple sclerosis. Cell Death Differ. 2010, 17:1083-91.
[77]Kidd PM: Neurodegeneration from mitochondrial insufficiency: nutrients, stem cells, growth factors, and prospects for brain rebuilding using integrative management. Altern Med Rev. 2005, 10:268-93.
[78]Witte ME, Nijland PG, Drexhage JA, Gerritsen W, Geerts D, van Het Hof B, et al.: Reduced expression of PGC-1α partly underlies mitochondrial changes and correlates with neuronal loss in multiple sclerosis cortex. Acta Neuropathol. 2013, 125:231-43.
[79]Blokhin A, Vyshkina T, Komoly S, Kalman B: Variations in mitochondrial DNA copy numbers in MS brains. J Mol Neurosci. 2008, 35:283-7.
[80]Lu F, Selak M, O’Connor J, Croul S, Lorenzana C, Butunoi C, et al.: Oxidative damage to mitochondrial DNA and activity of mitochondrial enzymes in chronic active lesions of multiple sclerosis. J Neurol Sci. 2000, 177:95-103.
[81]Dutta R, McDonough J, Yin X, Peterson J, Chang A, Torres T, et al.: Mitochondrial dysfunction as a cause of axonal degeneration in multiple sclerosis patients. Ann Neurol. 2006, 59:478-89.
[82]Mahad D, Lassmann H, Turnbull D: Review: Mitochondria and disease progression in multiple sclerosis. Neuropathol Appl Neurobiol. 2008, 34:577-89.
[83]Mahad DJ, Ziabreva I, Campbell G, Lax N, White K, Hanson PS, et al.: Mitochondrial changes within axons in multiple sclerosis. Brain. 2009, 132:1161-74.
[84]Reinke S, Broadhurst D, Sykes B, Baker G, Catz I, Warren K, et al.: Metabolomic profiling in multiple sclerosis: insights into biomarkers and pathogenesis. Mult Scler 2014, 20:1396-400.
[85]Lutz NW, Viola A, Malikova I, Confort-Gouny S, Ranjeva JP, Pelletier J, et al.: High-resolution 1 H NMR spectroscopy reveals differences in CSF metabolic profiles for MS patients with inflammatory vs. non-inflammatory plaques. Proc Intl Soc Mag Reson Med 2006, 14:1986.
[86]Lazzarino G, Amorini AM, Eikelenboom MJ, Killestein J, Belli A, Di Pietro V, et al.: Cerebrospinal fluid ATP metabolites in multiple sclerosis. Mult Scler. 2010, 16:549-54.
[87]Jeste SS, Geschwind DH: Disentangling the heterogeneity of autism spectrum disorder through genetic findings. Nat Rev Neurol. 2014, 10:74-81.
[88]Betancur C: Etiological heterogeneity in autism spectrum disorders: more than 100 genetic and genomic disorders and still counting. Brain Res. 2011, 1380:42-77.
[89]Wong CC, Meaburn EL, Ronald A, Price TS, Jeffries AR, Schalkwyk LC, et al.: Methylomic analysis of monozygotic twins discordant for autism spectrum disorder and related behavioural traits. Mol Psychiatry. 2014, 19:495-503.
[90]Hallmayer J, Cleveland S, Torres A, Phillips J, Cohen B, Torigoe T, et al.: Genetic heritability and shared environmental factors among twin pairs with autism. Arch Gen Psychiatry. 2011, 68:1095-102.
[91]Ronald A, Hoekstra RA: Autism spectrum disorders and autistic traits: a decade of new twin studies. Am J Med Genet B Neuropsychiatr Genet. 2011, 156B:255-74.
[92]Li X, Chauhan A, Sheikh AM, Patil S, Chauhan V, Li XM, et al.: Malik M. Elevated immune response in the brain of autistic patients. J Neuroimmunol 2009, 207:111-6.
[93]Morgan JT, Chana G, Pardo CA, Achim C, Semendeferi K, Buckwalter J, et al.: Microglial activation and increased microglial density observed in the dorsolateral prefrontal cortex in autism. Biol Psychiatry. 2010, 68:368-76.
[94]Goines P, Haapanen L, Boyce R, Duncanson P, Braunschweig D, Delwiche L, et al.: Autoantibodies to cerebellum in children with autism associate with behavior. Brain Behav Immun. 2011, 25:514-23.
[95]Onore C, Careaga M, Ashwood P: The role of immune dysfunction in the pathophysiology of autism. Brain Behav Immun. 2012, 26:383-92.
[96]Vargas DL, Nascimbene C, Krishnan C, Zimmerman AW, Pardo CA: Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol. 2005, 57:67-81.
[97]Grigorenko EL, Han SS, Yrigollen CM, Leng L, Mizue Y, Anderson GM, et al.: Macrophage migration inhibitory factor and autism spectrum disorders. Pediatrics. 2008, 122:e438-45.
[98]Voineagu I, Wang X, Johnston P, Lowe JK, Tian Y, Horvath S, et al.: Transcriptomic analysis of autistic brain reveals convergent molecular pathology. Nature. 2011, 474:380-4.
[99]Ziats MN, Rennert OM: Expression profiling of autism candidate genes during human brain development implicates central immune signaling pathways. PLoS One. 2011, 6:e24691.
[100]DeFelice ML, Ruchelli ED, Markowitz JE, Strogatz M, Reddy KP, Kadivar K, et al.: Intestinal cytokines in children with pervasive developmental disorders. Am J Gastroenterol. 2003, 98:1777-82.
[101]Ashwood P, Anthony A, Torrente F, Wakefield AJ: Spontaneous mucosal lymphocyte cytokine profiles in children with autism and gastrointestinal symptoms: mucosal immune activation and reduced counter regulatory interleukin-10. J Clin Immunol. 2004, 24:664-73.
[102]Molloy CA, Morrow AL, Meinzen-Derr J, Schleifer K, Dienger K, Manning-Courtney P, et al.: Elevated cytokine levels in children with autism spectrum disorder. J Neuroimmunol. 2006, 172:198-205.
[103]Ashwood P, Krakowiak P, Hertz-Picciotto I, Hansen R, Pessah I, et al.: Elevated plasma cytokines in autism spectrum disorders provide evidence of immune dysfunction and are associated with impaired behavioral outcome. Brain Behav Immun. 2011, 25:40-5.
[104]Suzuki K, Matsuzaki H, Iwata K, Kameno Y, Shimmura C, Kawai S, et al.: Plasma cytokine profiles in subjects with high-functioning autism spectrum disorders. PLoS One. 2011, 6:e20470.
[105]Emanuele E, Orsi P, Boso M, Broglia D, Brondino N, Barale F, et al.: Low-grade endotoxemia in patients with severe autism. Neurosci Lett. 2010, 471:162-5.
[106]Wei H, Zou H, Sheikh AM, Malik M, Dobkin C, Brown WT, et al.: IL-6 is increased in the cerebellum of autistic brain and alters neural cell adhesion, migration and synaptic formation. J Neuroinflammation. 2011, 8:52.
[107]Chez MG, Dowling T, Patel PB, Khanna P, Kominsky M: Elevation of tumor necrosis factor-alpha in cerebrospinal fluid of autistic children. Pediatr Neurol. 2007, 36:361-5.
[108]Chez M, Low R, Parise C, Donnel T: Safety and observations in a pilot study of lenalidomide for treatment in autism. Autism Res Treat. 2012, 2012:291601.
[109]Sweeten TL, Posey DJ, McDougle CJ: Brief report: autistic disorder in three children with cytomegalovirus infection. J Autism Dev Disord. 2004, 34:583-6.
[110]Singh VK: Plasma increase of interleukin-12 and interferon-gamma. Pathological significance in autism. J Neuroimmunol 1996, 66:143-5.
[111]Al-Gadani Y, El-Ansary A, Attas O, Al-Ayadhi L: Metabolic biomarkers related to oxidative stress and antioxidant status in Saudi autistic children. Clin Biochem. 2009, 42:1032-40.
[112]Melnyk S, Fuchs GJ, Schulz E, Lopez M, Kahler SG, Fussell JJ, et al.: Metabolic imbalance associated with methylation dysregulation and oxidative damage in children with autism. J Autism Dev Disord. 2012, 42:367-77.
[113]Rose S, Melnyk S, Trusty TA, Pavliv O, Seidel L, Li J, et al.: Intracellular and extracellular redox status and free radical generation in primary immune cells from children with autism. Autism Res Treat. 2012, 2012:986519.
[114]Rossignol DA, Frye RE: A review of research trends in physiological abnormalities in autism spectrum disorders: immune dysregulation, inflammation, oxidative stress, mitochondrial dysfunction and environmental toxicant exposures. Mol Psychiatry. 2012, 17:389-401.
[115]James SJ, Melnyk S, Jernigan S, Hubanks A, Rose S, Gaylor DW: Abnormal transmethylation/transsulfuration metabolism and DNA hypomethylation among parents of children with autism. J Autism Dev Disord. 2008, 38:1966-75.
[116]Boris M, Goldblatt A, Galanko J, James SJ: Association of MTHFR gene variants with autism. J Am Phys Surg. 2004, 9:106-8.
[117]James SJ, Melnyk S, Jernigan S, Cleves MA, Halsted CH, Wong DH, et al.: Metabolic endophenotype and related genotypes are associated with oxidative stress in children with autism. Am J Med Genet B Neuropsychiatr Genet. 2006, 141B:947-56.
[118]Bowers K, Li Q, Bressler J, Avramopoulos D, Newschaffer C, Fallin MD: Glutathione pathway gene variation and risk of autism spectrum disorders. J Neurodev Disord. 2011, 3:132-43.
[119]Frustaci A, Neri M, Cesario A, Adams JB, Domenici E, Dalla Bernardina B, et al.: Oxidative stress-related biomarkers in autism: systematic review and meta-analyses. Free Radic Biol Med. 2012, 52:2128-41.
[120]Goin-Kochel RP, Porter AE, Peters SU, Shinawi M, Sahoo T, Beaudet AL: The MTHFR 677C– > T polymorphism and behaviors in children with autism: exploratory genotype-phenotype correlations. Autism Res. 2009, 2:98-108.
[121]James SJ, Cutler P, Melnyk S, Jernigan S, Janak L, Gaylor DW, et al.: Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. Am J Clin Nutr. 2004, 80:1611-7.
[122]James SJ, Melnyk S, Fuchs G, Reid T, Jernigan S, Pavliv O, et al.: Efficacy of methylcobalamin and folinic acid treatment on glutathione redox status in children with autism. Am J Clin Nutr. 2009, 89:425-30.
[123]Ghezzo A, Visconti P, Abruzzo PM, Bolotta A, Ferreri C, Gobbi G, et al.: Oxidative stress and erythrocyte membrane alterations in children with autism: correlation with clinical features. PLoS One. 2013, 8:e66418.
[124]Adams JB, Baral M, Geis E, Mitchell J, Ingram J, Hensley A, et al.: The severity of autism is associated with toxic metal body burden and red blood cell glutathione levels. J Toxicol. 2009, 2009:532640.
[125]Gorrindo P, Lane CJ, Lee EB, McLaughlin B, Levitt P: Enrichment of elevated plasma F2t-isoprostane levels in individuals with autism who are stratified by presence of gastrointestinal dysfunction. PLoS One. 2013, 8:e68444.
[126]Chauhan A, Gu F, Essa MM, Wegiel J, Kaur K, Brown WT, et al.: Brain region-specific deficit in mitochondrial electron transport chain complexes in children with autism. J Neurochem. 2011, 117:209-20.
[127]Sajdel-Sulkowska EM, Xu M, McGinnis W, Koibuchi N: Brain region-specific changes in oxidative stress and neurotrophin levels in autism spectrum disorders (ASD). Cerebellum. 2011, 10:43-8.
[128]Chauhan A, Audhya T, Chauhan V: Brain region-specific glutathione redox imbalance in autism. Neurochem Res. 2012, 37:1681-9.
[129]Rose S, Melnyk S, Pavliv O, Bai S, Nick TG, Frye RE, et al.: Evidence of oxidative damage and inflammation associated with low glutathione redox status in the autism brain. Transl Psychiatry. 2012, 2:e134.
[130]Gu F, Chauhan V, Kaur K, Brown WT, LaFauci G, Wegiel J, et al.: Alterations in mitochondrial DNA copy number and the activities of electron transport chain complexes and pyruvate dehydrogenase in the frontal cortex from subjects with autism. Transl Psychiatry. 2013, 3:e299.
[131]Gu F, Chauhan V, Chauhan A: Impaired synthesis and antioxidant defense of glutathione in the cerebellum of autistic subjects: alterations in the activities and protein expression of glutathione-related enzymes. Free Radic Biol Med. 2013, 65:488-96.
[132]Tang G, Gutierrez Rios P, Kuo SH, Akman HO, Rosoklija G, Tanji K, et al.: Mitochondrial abnormalities in temporal lobe of autistic brain. Neurobiol Dis. 2013, 54:349-61.
[133]Giulivi C, Zhang YF, Omanska-Klusek A, Ross-Inta C, Wong S, Hertz-Picciotto I, et al.: Mitochondrial dysfunction in autism. JAMA. 2010, 304:2389-96.
[134]Guevara-Campos J, González-Guevara L, Briones P, López-Gallardo E, Bulán N, Ruiz-Pesini E, et al.: Autism associated to a deficiency of complexes III and IV of the mitochondrial respiratory chain. Invest Clin. 2010, 51:423-31.
[135]Shoffner J, Hyams L, Langley GN, Cossette S, Mylacraine L, Dale J, et al.: Fever plus mitochondrial disease could be risk factors for autistic regression. J Child Neurol. 2010, 25:429-34.
[136]Zhang B, Angelidou A, Alysandratos KD, Vasiadi M, Francis K, Asadi S, et al.: Mitochondrial DNA and anti-mitochondrial antibodies in serum of autistic children. J Neuroinflammation. 2010, 7:80.
[137]Dhillon S, Hellings JA, Butler MG: Genetics and mitochondrial abnormalities in autism spectrum disorders: a review. Curr Genomics. 2011, 12:322-32.
[138]Frye RE, Delatorre R, Taylor H, Slattery J, Melnyk S, Chowdhury N, et al.: Redox metabolism abnormalities in autistic children associated with mitochondrial disease. Transl Psychiatry. 2013, 3:e273.
[139]Frye RE, Rossignol DA: Mitochondrial physiology and autism spectrum disorder. OA Autism. 2013, 1:5.
[140]Minshew NJ, Goldstein G, Dombrowski SM, Panchalingam K, Pettegrew JW: A preliminary 31P MRS study of autism: evidence for undersynthesis and increased degradation of brain membranes. Biol Psychiatry. 1993, 33:762-73.
[141]Mostafa GA, El-Gamal HA, El-Wakkad ASE, El-Shorbagy OE, Hamza MM: Polyunsaturated fatty acids, carnitine and lactate as biological markers of brain energy in autistic children. Int J Child Neuropsychiatry. 2005, 2:179-88.
[142]Frye RE: Biomarkers of abnormal energy metabolism in children with autism spectrum disorder. NAJ Med Sci. 2012, 5:141-7.
[143]Palmieri L, Papaleo V, Porcelli V, Scarcia P, Gaita L, Sacco R, et al.: Altered calcium homeostasis in autism-spectrum disorders: evidence from biochemical and genetic studies of the mitochondrial aspartate/glutamate carrier AGC1. Mol Psychiatry. 2010, 15:38-52.
[144]Anitha A, Nakamura K, Thanseem I, Yamada K, Iwayama Y, Toyota T, et al.: Brain region-specific altered expression and association of mitochondria-related genes in autism. Mol Autism. 2012, 3:12.
[145]Anitha A, Nakamura K, Thanseem I, Matsuzaki H, Miyachi T, Tsujii M, et al.: Downregulation of the expression of mitochondrial electron transport complex genes in autism brains. Brain Pathol. 2013, 23:294-302.
[146]Ginsberg MR, Rubin RA, Falcone T, Ting AH, Natowicz MR: Brain transcriptional and epigenetic associations with autism. PLoS One. 2012, 7:e44736.
[147]Chugani DC, Sundram BS, Behen M, Lee ML, Moore GJ: Evidence of altered energy metabolism in autistic children. Prog Europsychopharmacol Biol Psych. 1999, 23:635-41.
[148]Coleman M, Blass JP: Autism and lactic acidosis. J Autism Dev Disord. 1985, 15:1-8.
[149]Filipek PA, Juranek J, Nguyen MT, Cummings C, Gargus JJ: Relative carnitine deficiency in autism. J Autism Dev Disord. 2004, 34:615-23.
[150]Filipek PA, Juranek J, Smith M, Mays LZ, Ramos ER, Bocian M, et al.: Mitochondrial dysfunction in autistic patients with 15q inverted duplication. Ann Neurol. 2003, 53:801-4.
[151]Fillano JJ, Goldenthal MJ, Rhodes CH, Marín-García J: Mitochondrial dysfunction in patients with hypotonia, epilepsy, autism, and developmental delay: HEADD syndrome. J Child Neurol. 2002, 17:435-9.
[152]Holiga Š, Mueller K, Möller HE, Sieger T, Schroeter ML, Vymazal J, et al.: Motor matters: tackling heterogeneity of Parkinson’s disease in functional MRI studies. PLoS One. 2013, 8:e56133.
[153]Erro R, Vitale C, Amboni M, Picillo M, Moccia M, Longo K, et al.: The heterogeneity of early Parkinson’s disease: a cluster analysis on newly diagnosed untreated patients. PLoS One. 2013, 8:e70244.
[154]Beach TG, Adler CH, Sue LI, Vedders L, Lue L, White Iii CL, et al.: Arizona Parkinson’s Disease Consortium. Multi-organ distribution of phosphorylated alpha-synuclein histopathology in subjects with Lewy body disorders. Acta Neuropathol 2010, 119:689-702.
[155]Rentzos M, Nikolaou C, Andreadou E, Paraskevas GP, Rombos A, Zoga M, et al.: Circulating interleukin-10 and interleukin-12 in Parkinson’s disease. Acta Neurol Scand. 2009, 119:332-7.
[156]Reynolds AD, Glanzer JG, Kadiu I, Ricardo-Dukelow M, Chaudhuri A, Ciborowski P, et al.: Nitrated alpha-synuclein-activated microglial profiling for Parkinson’s disease. J Neurochem. 2008, 104:1504-25.
[157]Scalzo P, Kümmer A, Cardoso F, Teixeira AL: Increased serum levels of soluble tumor necrosis factor-alpha receptor-1 in patients with Parkinson’s disease. J Neuroimmunol. 2009, 216:122-5.
[158]Dufek M, Hamanová M, Lokaj J, Goldemund D, Rektorová I, Michálková Z, et al.: Serum inflammatory biomarkers in Parkinson’s disease. Parkinsonism Relat Disord. 2009, 15:318-20.
[159]Chen H, O’Reilly EJ, Schwarzschild MA, Ascherio A: Peripheral inflammatory biomarkers and risk of Parkinson’s disease. Am J Epidemiol. 2008, 167:90-5.
[160]Mogi M, Harada M, Kondo T, Riederer P, Inagaki H, Minami M, et al.: Interleukin-1 beta, interleukin-6, epidermal growth factor and transforming growth factor-alpha are elevated in the brain from parkinsonian patients. Neurosci Lett. 1994, 180:147-50.
[161]Mogi M, Harada M, Narabayashi H, Inagaki H, Minami M, Nagatsu T: Interleukin (IL)-1 beta, IL-2, IL-4, IL-6 and transforming growth factor-alpha levels are elevated in ventricular cerebrospinal fluid in juvenile parkinsonism and Parkinson’s disease. Neurosci Lett. 1996, 211:13-6.
[162]Nagatsu T, Mogi M, Ichinose H, Togari A: Cytokines in Parkinson’s disease. J Neural Transm Suppl. 2000, 2000:143-51.
[163]Mogi M, Harada M, Riederer P, Narabayashi H, Fujita K, Nagatsu T: Tumor necrosis factor-alpha (TNF-alpha) increases both in the brain and in the cerebrospinal fluid from parkinsonian patients. Neurosci Lett. 1994, 165:208-10.
[164]Hasegawa Y, Inagaki T, Sawada M, Suzumura A: Impaired cytokine production by peripheral blood mononuclear cells and monocytes/macrophages in Parkinson’s disease. Acta Neurol Scand. 2000, 101:159-64.
[165]Arai H, Furuya T, Mizuno Y, Mochizuki H: Inflammation and infection in Parkinson’s disease. Histol Histopathol. 2006, 21:673-8.
[166]Bosco DA, Fowler DM, Zhang Q, Nieva J, Powers ET, Wentworth P Jr, et al.: Elevated levels of oxidized cholesterol metabolites in Lewy body disease brains accelerate alpha-synuclein fibrilization. Nat Chem Biol. 2006, 2:249-53.
[167]Nakabeppu Y, Tsuchimoto D, Yamaguchi H, Sakumi K: Oxidative damage in nucleic acids and Parkinson’s disease. J Neurosci Res. 2007, 85:919-34.
[168]Zeevalk GD, Razmpour R, Bernard LP: Glutathione and Parkinson’s disease: is this the elephant in the room? Biomed Pharmacother. 2008, 62:236-49.
[169]Perry TL, Godin DV, Hansen S: Parkinson’s disease: a disorder due to nigral glutathione deficiency? Neurosci Lett. 1982, 33:305-10.
[170]Perry TL, Yong VW: Idiopathic Parkinson’s disease, progressive supranuclear palsy and glutathione metabolism in the substantia nigra of patients. Neurosci Lett. 1986, 67:269-74.
[171]Sofic E, Lange KW, Jellinger K, Riederer P: Reduced and oxidized glutathione in the substantia nigra of patients with Parkinson’s disease. Neurosci Lett. 1992, 142:128-30.
[172]Alam ZI, Daniel SE, Lees AJ, Marsden DC, Jenner P, Halliwell B: A generalised increase in protein carbonyls in the brain in Parkinson’s but not incidental Lewy body disease. J Neurochem. 1997, 69:1326-9.
[173]Floor E, Wetzel MG: Increased protein oxidation in human substantia nigra pars compacta in comparison with basal ganglia and prefrontal cortex measured with an improved dinitrophenylhydrazine assay. J Neurochem. 1998, 70:268-75.
[174]Alam ZI, Jenner A, Daniel SE, Lees AJ, Cairns N, Marsden CD, et al.: Oxidative DNA damage in the parkinsonian brain: an apparent selective increase in 8-hydroxyguanine levels in substantia nigra. J Neurochem. 1997, 69:1196-203.
[175]Yoritaka A, Hattori N, Uchida K, Tanaka M, Stadtman ER, Mizuno Y: Immunohistochemical detection of 4-hydroxynonenal protein adducts in Parkinson disease. Proc Natl Acad Sci U S A. 1996, 93:2696-701.
[176]Dexter DT, Carter CJ, Wells FR, Javoy-Agid F, Agid Y, Lees A, et al.: Basal lipid peroxidation in substantia nigra is increased in Parkinson’s disease. J Neurochem. 1989, 52:381-9.
[177]Giasson BI, Duda JE, Murray IV, Chen Q, Souza JM, Hurtig HI, et al.: Oxidative damage linked to neurodegeneration by selective alpha-synuclein nitration in synucleinopathy lesions. Science. 2000, 290:985-9.
[178]Chung KK, Thomas B, Li X, Pletnikova O, Troncoso JC, Marsh L, et al.: S-nitrosylation of parkin regulates ubiquitination and compromises parkin’s protective function. Science. 2004, 304:1328-31.
[179]Yao D, Gu Z, Nakamura T, Shi ZQ, Ma Y, Gaston B, et al.: Nitrosative stress linked to sporadic Parkinson’s disease: S-nitrosylation of parkin regulates its E3 ubiquitin ligase activity. Proc Natl Acad Sci U S A. 2004, 101:10810-4.
[180]Selley ML: (E)-4-hydroxy-2-nonenal may be involved in the pathogenesis of Parkinson’s disease. Free Radic Biol Med 1998, 25:169-74.
[181]Kikuchi A, Takeda A, Onodera H, Kimpara T, Hisanaga K, Sato N, et al.: Systemic increase of oxidative nucleic acid damage in Parkinson’s disease and multiple system atrophy. Neurobiol Dis. 2002, 9:244-8.
[182]Abe T, Isobe C, Murata T, Sato C, Tohgi H: Alteration of 8-hydroxyguanosine concentrations in the cerebrospinal fluid and serum from patients with Parkinson’s disease. Neurosci Lett. 2003, 336:105-8.
[183]Buhmann C, Arlt S, Kontush A, Möller-Bertram T, Sperber S, Oechsner M, et al.: Plasma and CSF markers of oxidative stress are increased in Parkinson’s disease and influenced by antiparkinsonian medication. Neurobiol Dis. 2004, 15:160-70.
[184]Sohmiya M, Tanaka M, Tak NW, Yanagisawa M, Tanino Y, Suzuki Y, et al.: Redox status of plasma coenzyme Q10 indicates elevated systemic oxidative stress in Parkinson’s disease. J Neurol Sci. 2004, 223:161-6.
[185]Prigione A, Begni B, Galbussera A, Beretta S, Brighina L, Garofalo R, et al.: Oxidative stress in peripheral blood mononuclear cells from patients with Parkinson’s disease: negative correlation with levodopa dosage. Neurobiol Dis. 2006, 23:36-43.
[186]Schapira AH, Cooper JM, Dexter D, Clark JB, Jenner P, Marsden CD: Mitochondrial complex I deficiency in Parkinson’s disease. J Neurochem. 1990, 54:823-7.
[187]Mizuno Y, Ohta S, Tanaka M, Takamiya S, Suzuki K, Sato T, et al.: Deficiencies in complex I subunits of the respiratory chain in Parkinson’s disease. Biochem Biophys Res Commun. 1989, 163:1450-5.
[188]Parker WD Jr, Parks JK, Swerdlow RH: Complex I deficiency in Parkinson’s disease frontal cortex. Brain Res. 2008, 1189:215-8.
[189]Bindoff LA, Birch-Machin MA, Cartlidge NE, Parker WD Jr, Turnbull DM: Respiratory chain abnormalities in skeletal muscle from patients with Parkinson’s disease. J Neurol Sci. 1991, 104:203-8.
[190]Haas RH, Nasirian F, Nakano K, Ward D, Pay M, Hill R, et al.: Low platelet mitochondrial complex I and complex II/III activity in early untreated Parkinson’s disease. Ann Neurol. 1995, 37:714-22.
[191]Keeney PM, Xie J, Capaldi RA, Bennett JP Jr: Parkinson’s disease brain mitochondrial complex I has oxidatively damaged subunits and is functionally impaired and misassembled. J Neurosci. 2006, 26:5256-64.
[192]Shinde S, Pasupathy K: Respiratory-chain enzyme activities in isolated mitochondria of lymphocytes from patients with Parkinson’s disease: preliminary study. Neurol India. 2006, 54:390-3.
[193]Rana M, de Coo I, Diaz F, Smeets H, Moraes CT: An out-of-frame cytochrome b gene deletion from a patient with parkinsonism is associated with impaired complex III assembly and an increase in free radical production. Ann Neurol. 2000, 48:774-81.
[194]Acín-Pérez R, Bayona-Bafaluy MP, Fernández-Silva P, Moreno-Loshuertos R, Pérez-Martos A, Bruno C, et al.: Respiratory complex III is required to maintain complex I in mammalian mitochondria. Mol Cell. 2004, 13:805-15.
[195]Rango M, Bonifati C, Bresolin N: Parkinson’s disease and brain mitochondrial dysfunction: a functional phosphorus magnetic resonance spectroscopy study. J Cereb Blood Flow Metab. 2006, 26:283-90.
[196]Hu MT, Taylor-Robinson SD, Chaudhuri KR, Bell JD, Labbé C, Cunningham VJ, et al.: Cortical dysfunction in non-demented Parkinson’s disease patients: a combined (31)P-MRS and (18)FDG-PET study. Brain. 2000, 123:340-52.
[197]Bowen BC, Block RE, Sanchez-Ramos J, Pattany PM, Lampman DA, Murdoch JB, et al.: Proton MR spectroscopy of the brain in 14 patients with Parkinson disease. AJNR Am J Neuroradiol. 1995, 16:61-8.
[198]Henchcliffe C, Beal MF: Mitochondrial biology and oxidative stress in Parkinson disease pathogenesis. Nat Clin Pract Neurol. 2008, 4:600-9.
[199]Metzger K, Frémont M, Roelant C, De Meirleir K: Lower frequency of IL-17 F sequence variant (His161Arg) in chronic fatigue syndrome patients. Biochem Biophys Res Commun. 2008, 376:231-3.
[200]Mihaylova I, DeRuyter M, Rummens JL, Bosmans E, Maes M: Decreased expression of CD69 in chronic fatigue syndrome in relation to inflammatory markers: evidence for a severe disorder in the early activation of T lymphocytes and natural killer cells. Neuro Endocrinol Lett. 2007, 28:477-83.
[201]Maes M, Mihaylova I, Leunis JC: In chronic fatigue syndrome, the decreased levels of omega-3 poly-unsaturated fatty acids are related to lowered serum zinc and defects in T cell activation. Neuro Endocrinol Lett. 2005, 26:745-51.
[202]Maes M, Twisk FN, Johnson C: Myalgic encephalomyelitis (ME), chronic fatigue syndrome (CFS), and chronic fatigue (CF) are distinguished accurately: results of supervised learning techniques applied on clinical and inflammatory data. Psychiatry Res. 2012, 200:754-60.
[203]Maher KJ, Klimas NG, Fletcher MA: Chronic fatigue syndrome is associated with diminished intracellular perforin. Clin Exp Immunol. 2005, 142:505-11.
[204]Broderick G, Fuite J, Kreitz A, Vernon SD, Klimas N, Fletcher MA: A formal analysis of cytokine networks in chronic fatigue syndrome. Brain Behav Immun. 2010, 24:1209-17.
[205]Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A: The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group. Ann Intern Med. 1994, 121:953-9.
[206]Brenu EW, van Driel ML, Staines DR, Ashton KJ, Hardcastle SL, Keane J, et al.: Longitudinal investigation of natural killer cells and cytokines in chronic fatigue syndrome/myalgic encephalomyelitis. J Transl Med. 2012, 10:88.
[207]Brenu EW, van Driel ML, Staines DR, Ashton KJ, Ramos SB, Keane J, et al.: Immunological abnormalities as potential biomarkers in chronic fatigue syndrome/myalgic encephalomyelitis. J Transl Med. 2011, 9:81.
[208]Lombardi VC, Hagen KS, Hunter KW, Diamond JW, Smith-Gagen J, Yang W, et al.: Xenotropic murine leukemia virus-related virus-associated chronic fatigue syndrome reveals a distinct inflammatory signature. In Vivo. 2011, 25:307-14.
[209]Moss RB, Mercandetti A, Vojdani A: TNF-alpha and chronic fatigue syndrome. J Clin Immunol. 1999, 19:314-6.
[210]Borish L, Schmaling K, DiClementi JD, Streib J, Negri J, Jones JF: Chronic fatigue syndrome: identification of distinct subgroups on the basis of allergy and psychologic variables. J Allergy Clin Immunol. 1998, 102:222-30.
[211]Patarca R, Klimas N, Lugtendorf S, Antoni M, Fletcher M: Dysregulated expression of tumor necrosis factor in chronic fatigue syndrome: interrelations with cellular sources and patterns of soluble immune mediator expression. Clin Infect Dis. 1994, 18:147-53.
[212]Brenu E, Johnston S, Hardcastle S, Huth T, Fuller K, Ramos S, et al.: Immune abnormalities in patients meeting new diagnostic criteria for chronic fatigue syndrome/myalgic encephalomyelitis. J Mol Biomark Diagn. 2013, 4:2.
[213]Natelson BH, Haghighi MH, Ponzio NM: Evidence for the presence of immune dysfunction in chronic fatigue syndrome. Clin Diagn Lab Immunol. 2002, 9:747-52.
[214]Natelson BH: Brain dysfunction as one cause of CFS symptoms including difficulty with attention and concentration. Front Physiol. 2013, 4:109.
[215]Bansal AS, Bradley AS, Bishop KN, Kiani-Alikhan S, Ford B: Chronic fatigue syndrome, the immune system and viral infection. Brain Behav Immun. 2012, 26:24-31.
[216]Kennedy G, Norris G, Spence V, McLaren M, Belch JJ: Is chronic fatigue syndrome associated with platelet activation? Blood Coagul Fibrinolysis. 2006, 17:89-92.
[217]Hickie I, Davenport T, Wakefield D, Vollmer-Conna U, Cameron B, Vernon SD, et al.: Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study. BMJ. 2006, 333:575.
[218]Scheeres K, Wensing M, Knoop H, Bleijenberg G: Implementing cognitive behavioral therapy for chronic fatigue syndrome in a mental health center: a benchmarking evaluation. J Consult Clin Psychol. 2008, 76:163-71.
[219]Reeves WC, Lloyd A, Vernon SD, Klimas N, Jason LA, Bleijenberg G, et al.: International Chronic Fatigue Syndrome Study Group. Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution. BMC Health Serv Res. 2003, 3:25.
[220]Sharpe MC, Archard LC, Banatvala JE, Borysiewicz LK, Clare AW, David A, et al.: A report–chronic fatigue syndrome: guidelines for research. J R Soc Med. 1991, 84:118-21.
[221]Bergner M, Bobbitt RA, Carter WB, Gilson BS: The Sickness Impact Profile: development and final revision of a health status measure. Med Care. 1981, 19:787-805.
[222]Perrin R, Embleton K, Pentreath VW, Jackson A: Longitudinal MRI shows no cerebral abnormality in chronic fatigue syndrome. Br J Radiol. 2010, 83:419-23.
[223]Filler K, Lyon D, Bennett J, McCain N, Elswisk R, Lukkahatai N, et al.: Association of mitochondrial dysfunction and fatigue: a review of the literature. BBA Clinical. 2014, 1:12-23.
[224]Smits B, van den Heuvel L, Knoop H, Küsters B, Janssen A, Borm G, et al.: Mitochondrial enzymes discriminate between mitochondrial disorders and chronic fatigue syndrome. Mitochondrion. 2011, 11:735-8.
[225]Maes M, Mihaylova I, Leunis JC: Chronic fatigue syndrome is accompanied by an IgM-related immune response directed against neopitopes formed by oxidative or nitrosative damage to lipids and proteins. Neuro Endocrinol Lett. 2006, 27:615-21.
[226]Maes M, Mihaylova I, Kubera M, Uytterhoeven M, Vrydags N, Bosmans E: Increased 8-hydroxy-deoxyguanosine, a marker of oxidative damage to DNA, in major depression and myalgic encephalomyelitis/chronic fatigue syndrome. Neuro Endocrinol Lett. 2009, 30:715-22.
[227]Maes M, Mihaylova I, Kubera M, Uytterhoeven M, Vrydags N, Bosmans E: Coenzyme Q10 deficiency in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is related to fatigue, autonomic and neurocognitive symptoms and is another risk factor explaining the early mortality in ME/CFS due to cardiovascular disorder. Neuro Endocrinol Lett. 2009, 30:470-6.
[228]Maes M, Kubera M, Uytterhoeven M, Vrydags N, Bosmans E: Increased plasma peroxides as a marker of oxidative stress in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Med Sci Monit. 2011, 17:SC11-5.
[229]Vecchiet J, Cipollone F, Falasca K, Mezzetti A, Pizzigallo E, Bucciarelli T, et al.: Relationship between musculoskeletal symptoms and blood markers of oxidative stress in patients with chronic fatigue syndrome. Neurosci Lett. 2003, 335:151-4.
[230]Kennedy G, Spence VA, McLaren M, Hill A, Underwood C, Belch JJ: Oxidative stress levels are raised in chronic fatigue syndrome and are associated with clinical symptoms. Free Radic Biol Med. 2005, 39:584-9.
[231]Richards RS, Roberts TK, McGregor NR, Dunstan RH, Butt HL: Blood parameters indicative of oxidative stress are associated with symptom expression in chronic fatigue syndrome. Redox Rep. 2000, 5:35-41.
[232]Shungu DC, Weiduschat N, Murrough JW, Mao X, Pillemer S, Dyke JP, et al.: Increased ventricular lactate in chronic fatigue syndrome. III. Relationships to cortical glutathione and clinical symptoms implicate oxidative stress in disorder pathophysiology. NMR Biomed 2012, 25:1073-87.
[233]Miwa K, Fujita M: Fluctuation of serum vitamin E (alpha-tocopherol) concentrations during exacerbation and remission phases in patients with chronic fatigue syndrome. Heart Vessels. 2010, 25:319-23.
[234]Manuel y Keenoy B, Moorkens G, Vertommen J, Noe M, Nève J, De Leeuw I: Magnesium status and parameters of the oxidant-antioxidant balance in patients with chronic fatigue: effects of supplementation with magnesium. J Am Coll Nutr 2000, 19:374-82.
[235]Manuel y Keenoy B, Moorkens G, Vertommen J, De Leeuw I: Antioxidant status and lipoprotein peroxidation in chronic fatigue syndrome. Life Sci 2001, 68:2037-49.
[236]Maes M, Mihaylova I, Kubera M, Bosmans E: Not in the mind but in the cell: increased production of cyclo-oxygenase-2 and inducible NO synthase in chronic fatigue syndrome. Neuro Endocrinol Lett. 2007, 28:463-9.
[237]Fulle S, Pietrangelo T, Mancinelli R, Saggini R, Fanò G: Specific correlations between muscle oxidative stress and chronic fatigue syndrome: a working hypothesis. J Muscle Res Cell Motil. 2007, 28:355-62.
[238]Myhill S, Booth NE, McLaren-Howard J: Chronic fatigue syndrome and mitochondrial dysfunction. Int J Clin Exp Med. 2009, 2:1-16.
[239]Booth NE, Myhill S, McLaren-Howard J: Mitochondrial dysfunction and the pathophysiology of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Int J Clin Exp Med. 2012, 5:208-20.
[240]Myhill S, Booth NE, McLaren-Howard J: Targeting mitochondrial dysfunction in the treatment of myalgic ncephalomyelitis/chronic fatigue syndrome (ME/CFS) – a clinical audit. Int J Clin Exp Med. 2013, 6:1-15.
[241]Behan W, Holt I, Kay D, Moonie P: In vitro study of muscle aerobic metabolism in chronic fatigue syndrome. JCFS. 1999, 5:3-16.
[242]Behan WMH, More IAR, Downie I, Gow JW: Mitochondrial studies in the chronic fatigue syndrome. EOS Riv Immunol Immunofarmacol. 1995, 15:36-9.
[243]Behan WMH, Gow JW, Simpson K, More IAR, Downie I, Holt IJ, et al.: Mitochondrial findings in the chronic fatigue syndrome. J Pathol. 1994, 173:SI7.
[244]Behan WM, More IA, Behan PO: Mitochondrial abnormalities in the postviral fatigue syndrome. Acta Neuropathol. 1991, 83:61-5.
[245]Jones DE, Hollingsworth KG, Taylor R, Blamire AM, Newton JL: Abnormalities in pH handling by peripheral muscle and potential regulation by the autonomic nervous system in chronic fatigue syndrome. J Intern Med. 2010, 267:394-401.
[246]Hollingsworth KG, Jones DE, Taylor R, Blamire AM, Newton JL: Impaired cardiovascular response to standing in chronic fatigue syndrome. Eur J Clin Invest. 2010, 40:608-15.
[247]McCully KK, Natelson BH: Impaired oxygen delivery to muscle in chronic fatigue syndrome. Clin Sci (Lond). 1999, 97:603-8.
[248]McCully KK, Natelson BH, Iotti S, Sisto S, Leigh JS Jr: Reduced oxidative muscle metabolism in chronic fatigue syndrome. Muscle Nerve. 1996, 19:621-5.
[249]Wong R, Lopaschuk G, Zhu G, Walker D, Catellier D, Burton D, et al.: Skeletal muscle metabolism in the chronic fatigue syndrome. In vivo assessment by 31P nuclear magnetic resonance spectroscopy. Chest. 1992, 102:1716-22.
[250]Arnold DL, Bore PJ, Radda GK, Styles P, Taylor DJ: Excessive intracellular acidosis of skeletal muscle on exercise in a patient with a post-viral exhaustion/fatigue syndrome. A 31P nuclear magnetic resonance study. Lancet. 1984, 1:1367-9.
[251]Lane RJ, Soteriou BA, Zhang H, Archard LC: Enterovirus related metabolic myopathy: a postviral fatigue syndrome. J Neurol Neurosurg Psychiatry. 2003, 74:1382-6.
[252]Lane RJ, Barrett MC, Woodrow D, Moss J, Fletcher R, Archard LC: Muscle fibre characteristics and lactate responses to exercise in chronic fatigue syndrome. J Neurol Neurosurg Psychiatry. 1998, 64:362-7.
[253]Lane RJ, Barrett MC, Taylor DJ, Kemp GJ, Lodi R: Heterogeneity in chronic fatigue syndrome: evidence from magnetic resonance spectroscopy of muscle. Neuromuscul Disord. 1998, 8:204-9.
[254]Barnes PR, Taylor DJ, Kemp GJ, Radda GK: Skeletal muscle bioenergetics in the chronic fatigue syndrome. J Neurol Neurosurg Psychiatry. 1993, 56:679-83.
[255]Vermeulen RC, Kurk RM, Visser FC, Sluiter W, Scholte HR: Patients with chronic fatigue syndrome performed worse than controls in a controlled repeated exercise study despite a normal oxidative phosphorylation capacity. J Transl Med. 2010, 8:93.
[256]Vermeulen RC, Vermeulen van Eck IW: Decreased oxygen extraction during cardiopulmonary exercise test in patients with chronic fatigue syndrome. J Transl Med. 2014, 12:20.
[257]Mathew SJ, Mao X, Keegan KA, Levine SM, Smith EL, Heier LA, et al.: Ventricular cerebrospinal fluid lactate is increased in chronic fatigue syndrome compared with generalized anxiety disorder: an in vivo 3.0 T (1)H MRS imaging study. NMR Biomed. 2009, 22:251-8.
[258]Stork C, Renshaw PF: Mitochondrial dysfunction in bipolar disorder: evidence from magnetic resonance spectroscopy research. Mol Psychiatry. 2005, 10:900-19.
[259]Rajasekaran A, Venkatasubramanian G, Berk M, Debnath M: Mitochondrial dysfunction in schizophrenia: pathways, mechanisms, and implications. Neurosci Biobehav Rev. 2015, 48C:10-21.
[260]Eaton WW, Pedersen MG, Nielsen PR, Mortensen PB: Autoimmune diseases, bipolar disorder, and non-affective psychosis. Bipolar Disord. 2010, 12:638-46.
[261]Wadee AA, Kuschke RH, Wood LA, Berk M, Ichim L, Maes M: Serological observations in patients suffering from acute manic episodes. Hum Psychopharmacol. 2002, 17:175-9.
[262]Tsai SY, Chen KP, Yang YY, Chen CC, Lee JC, Singh VK, et al.: Activation of indices of cell-mediated immunity in bipolar mania. Biol Psychiatry. 1999, 45:989-94.
[263]Andreazza AC, Kapczinski F, Kauer-Sant’Anna M, Walz JC, Bond DJ, Gonçalves CA, et al.: 3-Nitrotyrosine and glutathione antioxidant system in patients in the early and late stages of bipolar disorder. J Psychiatry Neurosci. 2009, 34:263-71.
[264]Kauer-Sant’Anna M, Kapczinski F, Andreazza AC, Bond DJ, Lam RW, Young LT, et al.: Brain-derived neurotrophic factor and inflammatory markers in patients with early- vs. late-stage bipolar disorder. Int J Neuropsychopharmacol 2009, 12:447-58.
[265]Munkholm K, Braüner JV, Kessing LV, Vinberg M: Cytokines in bipolar disorder vs. healthy control subjects: a systematic review and meta-analysis. J Psychiatr Res 2013, 47:1119-33.
[266]Rosenblat JD, Cha DS, Mansur RB, McIntyre RS: Inflamed moods: a review of the interactions between inflammation and mood disorders. Prog Neuropsychopharmacol Biol Psychiatry. 2014, 53C:23-34.
[267]Ng F, Berk M, Dean O, Bush AI: Oxidative stress in psychiatric disorders: evidence base and therapeutic implications. Int J Neuropsychopharmacol. 2008, 11:851-76.
[268]Gawryluk JW, Wang JF, Andreazza AC, Shao L, Young LT: Decreased levels of glutathione, the major brain antioxidant, in post-mortem prefrontal cortex from patients with psychiatric disorders. Int J Neuropsychopharmacol. 2011, 14:123-30.
[269]Brown NC, Andreazza AC, Young LT: An updated meta-analysis of oxidative stress markers in bipolar disorder. Psychiatry Res. 2014, 218:61-8.
[270]Andreazza AC, Kauer-Sant’anna M, Frey BN, Bond DJ, Kapczinski F, Young LT, et al.: Oxidative stress markers in bipolar disorder: a meta-analysis. J Affect Disord. 2008, 111:135-44.
[271]Yumru M, Savas HA, Kalenderoglu A, Bulut M, Celik H, Erel O: Oxidative imbalance in bipolar disorder subtypes: a comparative study. Prog Neuropsychopharmacol Biol Psychiatry. 2009, 33:1070-4.
[272]Park SW, Lee CH, Lee JG, Kim LW, Shin BS, Lee BJ, et al.: Protective effects of atypical antipsychotic drugs against MPP(+)-induced oxidative stress in PC12 cells. Neurosci Res. 2011, 69:283-90.
[273]Padurariu M, Ciobica A, Dobrin I, Stefanescu C: Evaluation of antioxidant enzymes activities and lipid peroxidation in schizophrenic patients treated with typical and atypical antipsychotics. Neurosci Lett. 2010, 479:317-20.
[274]Jornada LK, Valvassori SS, Steckert AV, Moretti M, Mina F, Ferreira CL, et al.: Lithium and valproate modulate antioxidant enzymes and prevent ouabain-induced oxidative damage in an animal model of mania. J Psychiatr Res. 2011, 45:162-8.
[275]Cui J, Shao L, Young LT, Wang JF: Role of glutathione in neuroprotective effects of mood stabilizing drugs lithium and valproate. Neuroscience. 2007, 144:1447-53.
[276]Selek S, Savas HA, Gergerlioglu HS, Bulbul F, Uz E, Yumru M: The course of nitric oxide and superoxide dismutase during treatment of bipolar depressive episode. J Affect Disord. 2008, 107:89-94.
[277]Moylan S, Berk M, Dean OM, Samuni Y, Williams LJ, O’Neil A, et al.: Oxidative & nitrosative stress in depression: Why so much stress? Neurosci Biobehav Rev. 2014, 45C:46-62.
[278]Baxter LR Jr, Phelps ME, Mazziotta JC, Schwartz JM, Gerner RH, Selin CE, et al.: Cerebral metabolic rates for glucose in mood disorders. Studies with positron emission tomography and fluorodeoxyglucose F 18. Arch Gen Psychiatry 1985, 42:441-7.
[279]Kato T, Kato N: Mitochondrial dysfunction in bipolar disorder. Bipolar Disord. 2000, 2:180-90.
[280]Cataldo AM, McPhie DL, Lange NT, Punzell S, Elmiligy S, Ye NZ, et al.: Abnormalities in mitochondrial structure in cells from patients with bipolar disorder. Am J Pathol. 2010, 177:575-85.
[281]Michael N, Erfurth A, Ohrmann P, Gössling M, Arolt V, Heindel W, et al.: Acute mania is accompanied by elevated glutamate/glutamine levels within the left dorsolateral prefrontal cortex. Psychopharmacology (Berl). 2003, 168:344-6.
[282]Hamakawa H, Murashita J, Yamada N, Inubushi T, Kato N, Kato T: Reduced intracellular pH in the basal ganglia and whole brain measured by 31P-MRS in bipolar disorder. Psychiatry Clin Neurosci. 2004, 58:82-8.
[283]Regenold WT, Phatak P, Marano CM, Sassan A, Conley RR, Kling MA: Elevated cerebrospinal fluid lactate concentrations in patients with bipolar disorder and schizophrenia: implications for the mitochondrial dysfunction hypothesis. Biol Psychiatry. 2009, 65:489-94.
[284]Konradi C, Eaton M, MacDonald ML, Walsh J, Benes FM, Heckers S: Molecular evidence for mitochondrial dysfunction in bipolar disorder. Arch Gen Psychiatry. 2004, 61:300-8.
[285]Sun X, Wang JF, Tseng M, Young LT: Downregulation in components of the mitochondrial electron transport chain in the postmortem frontal cortex of subjects with bipolar disorder. J Psychiatry Neurosci. 2006, 31:189-96.
[286]Dean OM, Turner A, Malhi GS, Ng C, Cotton SM, et al. Design and rationale of a 16-week adjunctive randomized placebo-controlled trial of mitochondrial agents for the treatment of bipolar depression. Rev Bras Psiquiatr. 2014;0:0 [Epub ahead of print].
[287]Maes M, Bosmans E, Suy E, Vandervorst C, De Jonckheere C, Raus J. Immune disturbances during major depression: upregulated expression of interleukin-2 receptors. Neuropsychobiology. 1990–1991;24:115–20.
[288]Maes M: Depression is an inflammatory disease, but cell-mediated immune activation is the key component of depression. Prog Neuropsychopharmacol Biol Psychiatry. 2011, 35:664-75.
[289]Maes M, Mihaylova I, Kubera M, Ringel K: Activation of cell-mediated immunity in depression: association with inflammation, melancholia, clinical staging and the fatigue and somatic symptom cluster of depression. Prog Neuropsychopharmacol Biol Psychiatry. 2012, 36:169-75.
[290]Maes M, Lin AH, Delmeire L, Van Gastel A, Kenis G, De Jongh R, et al.: Elevated serum interleukin-6 (IL-6) and IL-6 receptor concentrations in posttraumatic stress disorder following accidental man-made traumatic events. Biol Psychiatry. 1999, 45:833-9.
[291]Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, et al.: A meta-analysis of cytokines in major depression. Biol Psychiatry. 2010, 67:446-57.
[292]Liu Y, Ho RC, Mak A: Interleukin (IL)-6, tumour necrosis factor alpha (TNF-α) and soluble interleukin-2 receptors (sIL-2R) are elevated in patients with major depressive disorder: a meta-analysis and meta-regression. J Affect Disord. 2012, 139:230-9.
[293]Howren MB, Lamkin DM, Suls J: Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosom Med. 2009, 71:171-86.
[294]Fornaro M, Rocchi G, Escelsior A, Contini P, Martino M: Might different cytokine trends in depressed patients receiving duloxetine indicate differential biological backgrounds. J Affect Disord. 2013, 145:300-7.
[295]Fornaro M, Bandini F, Ogliastro C, Cordano C, Martino M, Cestari L, et al.: Electroretinographic assessment in major depressed patients receiving duloxetine: Might differences between responders and non-responders indicate a differential biological background? J Affect Disord. 2011, 135:154-9.
[296]Song C, Halbreich U, Han C, Leonard B, Luo H: Imbalance between Pro- and Anti-inflammatory Cytokines, and between Th1 and Th2 Cytokines in Depressed Patients: The Effect of Electroacupuncture or Fluoxetine Treatment. Pharmacopsychiatry. 2009, 42:182-8.
[297]Maes M, Berk M, Goehler L, Song C, Anderson G, Gałecki P, et al.: Depression and sickness behavior are Janus-faced responses to shared inflammatory pathways. BMC Med. 2012, 10:66.
[298]Berk M, Kapczinski F, Andreazza AC, Dean OM, Giorlando F, Maes M, et al.: Pathways underlying neuroprogression in bipolar disorder: focus on inflammation, oxidative stress and neurotrophic factors. Neurosci Biobehav Rev. 2011, 35:804-17.
[299]Anderson G, Maes M. Oxidative/Nitrosative Stress and Immuno-inflammatory Pathways in Depression: Treatment Implications. Current Pharmaceutical Design. 2014;20(23):3812–3847. doi:10.2174/13816128113196660738.
[300]Maes M, Kubera M, Obuchowiczwa E, Goehler L, Brzeszcz J: Depression’s multiple comorbidities explained by (neuro)inflammatory and oxidative & nitrosative stress pathways. Neuroendocrinol Lett. 2011, 32:7-24.
[301]Raison CL, Miller AH: Is depression an inflammatory disorder? Curr Psychiatry Rep. 2011, 13:467-75.
[302]Gałecki P, Szemraj J, Bieńkiewicz M, Florkowski A, Gałecki E: Lipid peroxidation and antioxidant protection in patients during acute depressive episodes and in remission after fluoxetine treatment. Pharmacol Rep. 2009, 61:436-47.
[303]Forlenza MJ, Miller GE: Increased serum levels of 8-hydroxy-2’-deoxyguanosine in clinical depression. Psychosom Med. 2006, 68:1-7.
[304]Czarny P, Kwiatkowski D, Kacperska D, Kawczyńska D, Talarowska M, Orzechowska A, et al. Elevated Level of DNA Damage and Impaired Repair of Oxidative DNA Damage in Patients with Recurrent Depressive Disorder. Medical Science Monitor. 2015;21:412–418. doi:10.12659/msm.892317.
[305]Maes M, De Vos N, Pioli R, Demedts P, Wauters A, Neels H, et al.: Lower serum vitamin E concentrations in major depression. Another marker of lowered antioxidant defenses in that illness. J Affect Disord 2000, 58:241-6.
[306]Milaneschi Y, Cesari M, Simonsick E, Vogelzangs N, Kanaya A, Yaffe K, et al.: Lipid peroxidation and depressed mood in community-dwelling older men and women. Plos ONE. 2013, 8:e65406.
[307]Tsuboi H, Shimoi K, Kinae N, Oguni I, Hori R, Kobayashi F: Depressive symptoms are independently correlated with lipid peroxidation in a female population: comparison with vitamins and carotenoids. J Psychosom Res. 2004, 56:53-8.
[308]Yager S, Forlenza MJ, Miller GE: Depression and oxidative damage to lipids. Psychoneuroendocrinology. 2010, 35:1356-62.
[309]Miyaoka T, Yasukawa R, Yasuda H, Shimizu M, Mizuno S, Sukegawa T, et al.: Urinary excretion of biopyrrins, oxidative metabolites of bilirubin, increases in patients with psychiatric disorders. Eur Neuropsychopharmacol. 2005, 15:249-52.
[310]Berk M, Dean OM, Cotton SM, Jeavons S, Tanious M, Kohlmann K, et al.: The efficacy of adjunctive N-acetylcysteine in major depressive disorder: a double-blind, randomized, placebo-controlled trial. J Clin Psychiatry. 2014, 75:628-36.
[311]Dean OM, Maes M, Ashton M, Berk L, Kanchanatawan B, Sughondhabirom A, et al.: Protocol and rationale-the efficacy of minocycline as an adjunctive treatment for major depressive disorder: a double blind, randomised. Placebo Controlled Trial Clin Psychopharmacol Neurosci. 2014, 12:180-8.
[312]Maes M, Kubera M, Mihaylova I, Geffard M, Galecki P, Leunis JC, et al.: Increased autoimmune responses against auto-epitopes modified by oxidative and nitrosative damage in depression: implications for the pathways to chronic depression and neuroprogression. J Affect Disord. 2013, 149:23-9.
[313]Nunes S, Vargas H, Prado E, Barbosa D, de Melo L, Moylan S, et al.: The shared role of oxidative stress and inflammation in major depressive disorder and nicotine dependence. Neurosci Biobehav Rev. 2013, 37:1336-45.
[314]Tobe E: Mitochondrial dysfunction, oxidative stress, and major depressive disorder. Neuropsychiatr Dis Treat. 2013, 9:567-73.
[315]Anglin R, Rosebush P, Mazurek M, Tarnopolsky M, Noseworthy M: The psychiatric manifestations of mitochondrial cytopathies: A clinical and MR spectroscopy investigation. Mitochondrion. 2011, 11:639-40.
[316]Maes M, Galecki P, Chang Y, Berk M: A review on the oxidative and nitrosative stress (O&NS) pathways in major depression and their possible contribution to the (neuro)degenerative processes in that illness. Prog Neuro-Psychopharmacol Biol Psychiatry. 2011, 35:676-92.
[317]Berk M, Williams L, Jacka F, O’Neil A, Pasco J, Moylan S, et al.: So depression is an inflammatory disease, but where does the inflammation come from? BMC Med. 2013, 11:200.
[318]Sarandol A, Sarandol E, Eker SS, Erdinc S, Vatansever E, Kirli S: Major depressive disorder is accompanied with oxidative stress: short-term antidepressant treatment does not alter oxidative-antioxidative systems. Hum Psychopharmacol. 2007, 22:67-73.
[319]Irie M, Asami S, Nagata S, Ikeda M, Miyata M, Kasai H: Psychosocial factors as a potential trigger of oxidative DNA damage in human leukocytes. Jpn J Cancer Res. 2001, 92:367-76.
[320]Irie M, Miyata M, Kasia H: Depression and possible cancer risk due to oxidative DNA damage. J Psychiatr Res. 2005, 39:553-60.
[321]Drevets WC, Price JL, Simpson JR, Todd RD, Reich T, Vannier M, et al.: Subgenual prefrontal cortex abnormalities in mood disorders. Nature. 1997, 386:824-7.
[322]Fattal O, Budur K, Vaughan AJ, Franco K: Review of the literature on major mental disorders in adult patients with mitochondrial diseases. Psychosomatics. 2006, 47:1-7.
[323]Klinedinst N, Regenold W. A mitochondrial bioenergetic basis of depression. Journal Of Bioenergetics And Biomembranes. 2014;47(1-2):155–171. doi:10.1007/s10863-014-9584-6.
[324]Videbech P: PET measurements of brain glucose metabolism and blood flow in major depressive disorder: a critical review. Acta Psychiatr Scand. 2000, 101:11-20.
[325]Mayberg HS, Liotti M, Brannan SK, McGinnis S, Mahurin RK, Jerabek PA, et al.: Reciprocal limbic-cortical function and negative mood: converging PET findings in depression and normal sadness. Am J Psychiatry. 1999, 156:675-82.
[326]Moretti A, Gorini A, Villa R: Affective disorders, antidepressant drugs and brain metabolism. Mol Psychiatry. 2003, 8:773-85.
[327]Rigucci S, Serafini G, Pompili M, Kotzalidis G, Tatarelli R: Anatomical and functional correlates in major depressive disorder: the contribution of neuroimaging studies. World J Biol Psychiatry. 2010, 11:165-80.
[328]Gardner A, Johansson A, Wibom R, Nennesmo I, von Dobeln U, Hagenfeldt L, et al.: Alterations of mitochondrial function and correlations with personality traits in selected major depressive disorder patients. J Affect Disord. 2003, 76:55-68.
[329]Hroudová J, Fišar Z, Kitzlerová E, Zvěřová M, Raboch J: Mitochondrial respiration in blood platelets of depressive patients. Mitochondrion. 2013, 6:795-800.
[330]Karabatsiakis A, Böck C, Salinas-Manrique J, Kolassa S, Calzia E, Dietrich E, et al.: Mitochondrial respiration in peripheral blood mononuclear cells correlates with depressive subsymptoms and severity of major depression. Translational Psychiatry. 2014, 4:e397.
[331]Rothermundt M, Arolt V, Weitzsch C, Eckhoff D, Kirchner H: Immunological dysfunction in schizophrenia: a systematic approach. Neuropsychobiology. 1998, 37:186-93.
[332]Theodoropoulou S, Spanakos G, Baxevanis CN, Economou M, Gritzapis AD, Papamichail MP, et al.: Cytokine serum levels, autologous mixed lymphocyte reaction and surface marker analysis in never medicated and chronically medicated schizophrenic patients. Schizophr Res. 2001, 47:13-25.
[333]Kim YK, Myint AM, Verkerk R, Scharpe S, Steinbusch H, Leonard B: Cytokine changes and tryptophan metabolites in medication-naïve and medication-free schizophrenic patients. Neuropsychobiology. 2009, 59:123-9.
[334]Kim YK, Myint AM, Lee BH, Han CS, Lee HJ, Kim DJ, et al.: Th1, Th2 and Th3 cytokine alteration in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2004, 28:1129-34.
[335]Zhang XY, Zhou DF, Zhang PY, Wu GY, Cao LY, Shen YC: Elevated interleukin-2, interleukin-6 and interleukin-8 serum levels in neuroleptic-free schizophrenia: association with psychopathology. Schizophr Res. 2002, 57:247-58.
[336]Potvin S, Stip E, Sepehry AA, Gendron A, Bah R, Kouassi E: Inflammatory cytokine alterations in schizophrenia: a systematic quantitative review. Biol Psychiatry. 2008, 63:801-8.
[337]Debnath M, Berk M: Th17 pathway-mediated immunopathogenesis of schizophrenia: mechanisms and implications. Schizophr Bull. 2014, 40:1412-21.
[338]Na K, Jung H, Kim Y: The role of pro-inflammatory cytokines in the neuroinflammation and neurogenesis of schizophrenia. Prog NeuroPsychopharmacol Biol Psychiatry. 2014, 48:277-86.
[339]Song X, Fan X, Li X, Zhang W, Gao J, Zhao J, et al.: Changes in pro-inflammatory cytokines and body weight during 6-month risperidone treatment in drug naïve, first-episode schizophrenia. Psychopharmacology (Berl). 2013, 231:319-25.
[340]Song X, Fan X, Song X, Zhang J, Zhang W, Li X, et al.: Elevated levels of adiponectin and other cytokines in drug naive, first episode schizophrenia patients with normal weight. Schizophr Res. 2013, 150:269-73.
[341]Ding M, Song X, Zhao J, Gao J, Li X, Yang G, et al.: Activation of Th17 cells in drug naïve, first episode schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2014, 51:78-82.
[342]Kirkpatrick B, Miller BJ: Inflammation and schizophrenia. Schizophr Bull. 2013, 39:1174-9.
[343]Martínez-Cengotitabengoa M, Mac-Dowell KS, Leza JC, Micó JA, Fernandez M, Echevarría E, et al.: Cognitive impairment is related to oxidative stress and chemokine levels in first psychotic episodes. Schizophr Res. 2012, 137:66-72.
[344]Pavlović D, Tamburić V, Stojanović I, Kocić G, Jevtović T, Đorđević V: Oxidative stress as marker of positive symptoms in schizophrenia. Facta Universitatis. 2002, 9:157-61.
[345]Wood SJ, Yücel M, Pantelis C, Berk M: Neurobiology of schizophrenia spectrum disorders: the role of oxidative stress. Ann Acad Med Singapore. 2009, 38:396.
[346]Bitanihirwe BKY, Woo TUW: Oxidative stress in schizophrenia: an inte-grated approach. Neurosci Biobehav Rev. 2011, 35:878-93.
[347]O’Donnell P, Do KQ, Arango C: Oxidative/nitrosative stress in psychiatricdisorders: are we there yet? Schizophr Bull. 2014, 40:960-2.
[348]Davis J, Moylan S, Harvey BH, Maes M, Berk M: Neuroprogression inschizophrenia: pathways underpinning clinical staging and therapeutic corol-laries. Aust NZ J Psychiatry. 2014, 48:512-29.
[349]Singh OP, Chakraborty I, Datta S: A comparative study of oxidative stressand interrelationship of important antioxidants in haloperidol and olanzap-ine treated patients suffering from schizophrenia. Indian J Psychiatry. 2008, 50:1-8.
[350]Raffa M, Mechri A, Othman L, Ben Fendri C, Gaha L, Kerkeni A: Decreased glutathione levels and antioxidant enzyme activities in untreated and treatedschizophrenic patients. Prog Neuropsychopharmacol Biol Psychiatry. 2009, 33:1178-83.
[351]Do K, Trabesinger A, Kirsten-Krüger M, Lauer C, Dydak U, Hell D, et al.: Schizophrenia: glutathione deficit in cerebrospinal fluid and prefrontal cortex in vivo. Eur J Neurosci. 2000, 12:3721-8.
[352]Wang J, Shao L, Sun X, Young L: Increased oxidative stress in the anterior cingulate cortex of subjects with bipolar disorder and schizophrenia. Bipolar Disord. 2009, 11:523-9.
[353]Prabakaran S, Wengenroth M, Lockstone H, Lilley K, Leweke F, Bahn S: 2-D DIGE analysis of liver and red blood cells provides further evidence for oxidative stress in schizophrenia. J Proteome Res. 2007, 6:141-9.
[354]Yao J, Reddy R, McElhinny L, van Kammen D: Reduced status of plasma total antioxidant capacity in schizophrenia. Schizophr Res. 1998, 32:1-8.
[355]Reddy R: Reduced plasma antioxidants in first-episode patients with schizophrenia. Schizophr Res. 2003, 62:205-12.
[356]Dadheech G, Mishra S, Gautam S, Sharma P: Oxidative stress, α-tocopherol, ascorbic acid and reduced glutathione status in schizophrenics. Indian J Clin Biochem. 2006, 21:34-8.
[357]Akyol O, Herken H, Uz E, Fadillioğlu E, Unal S, Söğüt S, et al.: The indices of endogenous oxidative and antioxidative processes in plasma from schizophrenic patients. Prog Neuropsychopharmacol Biol Psychiatry. 2002, 26:995-1005.
[358]Pedrini M, Massuda R, Fries GR, de Bittencourt Pasquali MA, Schnorr CE, Moreira JC, et al.: Similarities inserum oxidative stress markers and inflammatory cytokines in patients withovertschizophrenia at early and late stages of chronicity? J Psychiatr Res. 2012, 46:819-24.
[359]Gubert C, Stertz L, Pfaffenseller B, Panizzutti BS, Rezin GT, Massuda R, et al.: Mitochondrial activity and oxidative stress markers in peripheral bloodmononuclear cells of patients with bipolar disorder, schizophrenia, and healthy subjects. J Psychiatr Res. 2013, 47:1396-402.
[360]Ben Othmen L, Mechri A, Fendri C, Bost M, Chazot G, Gaha L, et al.: Altered antioxidant defense system in clinically stable patients with schizophrenia and their unaffected siblings. Prog Neuropsychopharmacol Biol Psychiatry. 2008, 32:155-9.
[361]Dietrich-Muszalska A, Olas B, Rabe-Jablonska J: Oxidative stress in blood platelets from schizophrenic patients. Platelets. 2005, 16:386-91.
[362]Kunz M, Gama C, Andreazza A, Salvador M, Ceresér K, Gomes FA, et al.: Elevated serum superoxide dismutase and thiobarbituric acid reactive substances in different phases of bipolar disorder and in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2008, 32:1677-81.
[363]Davis J, Maes M, Andreazza A, McGrath JJ, Tye SJ, Berk M: Towards a classification of biomarkers of neuropsychiatric disease: from encompass to compass. Mol Psychiatry. 2014, 20:152-3.
[364]Flatow J, Buckley P, Miller BJ: Meta-analysis of oxidative stress in schizophrenia. Biol Psychiatry. 2013, 74:400-9.
[365]Park C, Park SK: Molecular links between mitochondrial dysfunctions andschizophrenia. Mol Cells. 2012, 33:105-10.
[366]Ben-Shachar D: Mitochondrial dysfunction in schizophrenia: a possible link-age to dopamine. J Neurochem. 2002, 83:1241-51.
[367]Uranova N, Orlovskaya D, Vikhreva O, Zimina I, Kolomeets N, Vostrikov V, et al.: Electron microscopy of oligodendroglia in severe mental illness. Brain Res Bull. 2001, 55:597-610.
[368]Kung L, Roberts RC: Mitochondrial pathology in human schizophrenic striatum: a postmortem. Synapse. 1999, 31:67-75.
[369]Kolomeets NS, Uranova N: Ultrastructural abnormalities of astrocytes inthe hippocampus in schizophrenia and duration of illness: a postortem morphometric study. World J Biol Psychiatry. 2010, 11:282-92.
[370]Inuwa IM, Peet M, Williams MA: QSAR modeling and transmission electronmicroscopy stereology of altered mitochondrial ultrastructure of white bloodcells in patients diagnosed as schizophrenic and treated with antipsychoticdrugs. Biotech Histochem. 2005, 80:133-7.
[371]Uranova N, Bonartsev P, Brusov O, Morozova M, Rachmanova V, Orlovskaya D: The ultrastructure of lymphocytes in schizophrenia. World J Biol Psychiatry. 2007, 8:30-7.
[372]Rosenfeld M, Brenner-Lavie H, Ari SGB, Kavushansky A, Ben-Shachar D: Perturbation in mitochondrial network dynamics and in complex Idependent cellular respiration in schizophrenia. Biol Psychiatry. 2011, 69:980-8.
[373]Dror N, Klein E, Karry R, Sheinkman A, Kirsh Z, Mazor M, et al.: State-dependent alterations in mitochondrial complex I activity in platelets: a potential peripheral marker for schizophrenia? Mol Psychiatry. 2002, 7:995-1001.
[374]Ben-Shachar D, Karry R: Sp1 expression is disrupted in schizophrenia; a possible mechanism for the abnormal expression of mitochondrial complex I genes, NDUFV1 and NDUFV2. PLoS One. 2007, 2:e817.
[375]Ben-Shachar D, Zuk R, Gazawi H, Reshef A, Sheinkman A, Klein E: Increased mitochondrial complex I activity in platelets of schizophrenic patients. Int J Neuropsychopharmacol. 1999, 2:245-53.
[376]Ben-Shachar D, Karry R: Neuroanatomical pattern of mitochondrial complex I pathology varies between schizophrenia, bipolar disorder and major depression. PLoS One. 2008, 3:e3676.
[377]Karry R, Klein E, Ben SD: Mitochondrial complex I subunits expres-sion is altered in schizophrenia: a postmortem study. Biol Psychiatry. 2004, 55:676-84.
[378]Akarsu S: Schizophrenia and mitochondrial dysfunction. Psikiyatride Guncel Yaklasimlar - Current Approaches In Psychiatry. 2014, 6:340-54.
[379]Rajasekaran A, Venkatasubramanian G, Berk M, Debnath M. Mitochondrial dysfunction in schizophrenia: Pathways, mechanisms and implications. Neuroscience & Biobehavioral Reviews. 2015;48:10–21. doi:10.1016/j.neubiorev.2014.11.005.
[380]Maurer I, Zierz S, Möller H: Evidence for a mitochondrial oxidative phos-phorylation defect in brains from patients with schizophrenia. Schizophr Res. 2001, 48:125-36.
[381]Manatt M, Chandra S: The effects of mitochondrial dysfunction in schizophrenia. J Med Genet Genomics. 2011, 3:84-94.
[382]Blass P: Glucose/mitochondria in neurological conditions. Int Rev Neurobiol. 2002, 51:325-76.
[383]Martins-de-Souza D, Gattaz WF, Schmitt A, Novello JC, Marangoni S, Turck CW, et al.: Proteome analysis of schizophrenia patients Wer-nicke’s area reveals an energy metabolism dysregulation. BMC Psychiatry. 2009, 30:17.
[384]Martins-de-Souza D, Maccarrone G, Wobrock T, Zerr I, Gormanns P, Reckow S, et al.: Proteome analysis of the thalamusand cerebrospinal fluid reveals glycolysis dysfunction and potential biomarkerscandidates for schizophrenia. J Psychiatr Res. 2010, 44:1176-89.
[385]Prabakaran S, Swatton JE, Ryan MM, Huffaker SJ, Huang JTJ, Griffin JL, et al.: Mitochondrial dysfunction in schizophrenia: evidence for compromisedbrain metabolism and oxidative stress. Mol Psychiatry 2004, 9:684-97. 643
[386]Volz H, Riehemann S, Maurer I, Smesny S, Sommer M, Rzanny R, et al.: Reduced phosphodiesters and high-energy phosphates in the frontal lobe ofschizophrenic patients: a31P chemical shift spectroscopic-imaging study. Biol Psychiatry. 2000, 41:954-61.
[387]Verge B, Alonso Y, Miralles C, Valero J, Vilella E, Boles RG, et al.: New evidence for the involvement of mitochondrial inheritance in schizophre-nia: results from a cross-sectional study evaluating the risk of illness in relativesof schizophrenia patients? J Clin Psychiatry. 2012, 73:684-90.
[388]Leonard B, Maes M. Mechanistic explanations how cell-mediated immune activation, inflammation and oxidative and nitrosative stress pathways and their sequels and concomitants play a role in the pathophysiology of unipolar depression. Neuroscience & Biobehavioral Reviews. 2012;36(2):764–785. doi:10.1016/j.neubiorev.2011.12.005.
[389]Li X, Sundquist J, Sundquist K: Age-specific familial risks of psychotic dis-orders and schizophrenia: a nation-wide epidemiological study from Sweden. Schizophr Res. 2007, 97:43-50.
[390]Flyckt L, Edman G, Venizelos N, Borg K: Aberrant tyrosine transport acrossthe fibroblast membrane in patients with schizophrenia—indications of maternal inheritance? J Psychiatr Res. 2011, 45:519-25.
[391]Marchbanks RM, Ryan M, Day INM, Owen M, McGuffin P, Whatley SA: A mitochondrial DNA sequence variant associated with schizophrenia andoxidative stress. Schizophr Res. 2003, 65:33-8.
[392]Ueno H, Nishigaki Y, Kong QP, Fuku N, Kojima S, Iwata N, et al.: Analysis of mitochondrial DNA variants in Japanese patients with schizophrenia. Mitochondrion. 2009, 9:385-93.
[393]Ichikawa T, Arai M, Miyashita M, Arai M, Obata N, Nohara I, et al.: Schizophrenia: maternal inher-itance and heteroplasmy of mtDNA mutations? Mol Genet Metab. 2012, 105:103-9.
[394]Nisoli E, Carruba MO: Nitric oxide and mitochondrial biogenesis. J Cell Sci. 2006, 119:2855-62.
[395]Stamler JS, Meissner G: Physiology of nitric oxide in skeletal muscle. Physiol Rev. 2001, 81:209-37.
[396]Sarti P, Forte E, Giuffrè A, Mastronicola D, Magnifico MC, Arese M: The chemical interplay between nitric oxide and mitochondrial cytochrome c oxidase: reactions, effectors and pathophysiology. Int J Cell Biol. 2012, 2012:571067.
[397]Erusalimsky JD, Moncada S: Nitric oxide and mitochondrial signaling: from physiology to pathophysiology. Arterioscler Thromb Vasc Biol. 2007, 27:2524-31.
[398]Xu W, Charles IG, Moncada S: Nitric oxide: orchestrating hypoxia regulation through mitochondrial respiration and the endoplasmic reticulum stress response. Cell Res. 2005, 15:63-5.
[399]Cadenas E: Mitochondrial free radical production and cell signaling. Mol Aspects Med. 2004, 25:17-26.
[400]Boveris A, Costa LE, Poderoso JJ, Carreras MC, Cadenas E: Regulation of mitochondrial respiration by oxygen and nitric oxide. Ann N Y Acad Sci. 2000, 899:121-35.
[401]Moncada S, Erusalimsky JD: Does nitric oxide modulate mitochondrial energy generation and apoptosis? Nat Rev Mol Cell Biol. 2002, 3:214-20.
[402]Brown GC, Borutaite V: Nitric oxide and mitochondrial respiration in the heart. Cardiovasc Res. 2007, 75:283-90.
[403]Brown GC, Borutaite V: Inhibition of mitochondrial respiratory complex I by nitric oxide, peroxynitrite and S-nitrosothiols. Biochim Biophys Acta. 2004, 1658:44-9.
[404]Poderoso JJ, Carreras MC, Lisdero C, Riobó N, Schöpfer F, Boveris A: Nitric oxide inhibits electron transfer and increases superoxide radical production in rat heart mitochondria and submitochondrial particles. Arch Biochem Biophys. 1996, 328:85-92.
[405]Blandini F, Braunewell KH, Manahan-Vaughan D, Orzi F, Sarti P: Neurodegeneration and energy metabolism: from chemistry to clinics. Cell Death Differ. 2004, 11:479-84.
[406]Shiva S, Oh JY, Landar AL, Ulasova E, Venkatraman A, Bailey SM, et al.: Nitroxia: the pathological consequence of dysfunction in the nitric oxide-cytochrome c oxidase signaling pathway. Free Radic Biol Med. 2005, 38:297-306.
[407]Cooper CE, Giulivi C: Nitric oxide regulation of mitochondrial oxygen consumption II: molecular mechanism and tissue physiology. Am J Physiol Cell Physiol. 2007, 292:C1993-2003.
[408]Sarti P, Giuffrè A, Barone MC, Forte E, Mastronicola D, Brunori M: Nitric oxide and cytochrome oxidase: reaction mechanisms from the enzyme to the cell. Free Radic Biol Med. 2003, 34:509-20.
[409]Cooper CE, Brown GC: The inhibition of mitochondrial cytochrome oxidase by the gases carbon monoxide, nitric oxide, hydrogen cyanide and hydrogen sulfide: chemical mechanism and physiological significance. J Bioenerg Biomembr. 2008, 40:533-9.
[410]Tengan CH, Rodrigues GS, Godinho RO: Nitric oxide in skeletal muscle: role on mitochondrial biogenesis and function. Int J Mol Sci. 2012, 13:17160-84.
[411]Zhang J, Jin B, Li L, Block ER, Patel JM: Nitric oxide-induced persistent inhibition and nitrosylation of active site cysteine residues of mitochondrial cytochrome-c oxidase in lung endothelial cells. Am J Physiol Cell Physiol. 2005, 288:C840-9.
[412]Galkin A, Moncada S: S-nitrosation of mitochondrial complex I depends on its structural conformation. J Biol Chem. 2007, 282:37448-53.
[413]Clementi E, Brown GC, Feelisch M, Moncada S: Persistent inhibition of cell respiration by nitric oxide: crucial role of S-nitrosylation of mitochondrial complex I and protective action of glutathione. Proc Natl Acad Sci U S A. 1998, 95:7631-6.
[414]Cooper CE, Davies NA, Psychoulis M, Canevari L, Bates TE, Dobbie MS, et al.: Nitric oxide and peroxynitrite cause irreversible increases in the K(m) for oxygen of mitochondrial cytochrome oxidase: in vitro and in vivo studies. Biochim Biophys Acta. 2003, 1607:27-34.
[415]Giuffrè A, Sarti P, D’Itri E, Buse G, Soulimane T, Brunori M: On the mechanism of inhibition of cytochrome c oxidase by nitric oxide. J Biol Chem. 1996, 271:33404-8.
[416]Mason MG, Nicholls P, Wilson MT, Cooper CE: Nitric oxide inhibition of respiration involves both competitive (heme) and noncompetitive (copper) binding to cytochrome c oxidase. Proc Natl Acad Sci U S A. 2006, 103:708-13.
[417]Antunes F, Boveris A, Cadenas E: On the mechanism and biology of cytochrome oxidase inhibition by nitric oxide. Proc Natl Acad Sci U S A. 2004, 101:16774-9.
[418]Antunes F, Boveris A, Cadenas E: On the biologic role of the reaction of NO with oxidized cytochrome c oxidase. Antioxid Redox Signal. 2007, 9:1569-79.
[419]Cooper CE: Nitric oxide and cytochrome oxidase: substrate, inhibitor or effector? Trends Biochem Sci. 2002, 27:33-9.
[420]Brookes PS, Bolaños JP, Heales SJ: The assumption that nitric oxide inhibits mitochondrial ATP synthesis is correct. FEBS Lett. 1999, 446:261-3.
[421]Bolaños JP, Almeida A, Moncada S: Glycolysis: a bioenergetic or a survival pathway? Trends Biochem Sci. 2010, 35:145-9.
[422]Almeida A, Almeida J, Bolaños JP, Moncada S: Different responses of astrocytes and neurons to nitric oxide: the role of glycolytically generated ATP in astrocyte protection. Proc Natl Acad Sci U S A. 2001, 98:15294-9.
[423]Warburg O: On respiratory impairment in cancer cells. Science. 1956, 124:269-70.
[424]Arese M, Magnifico MC, Mastronicola D, Altieri F, Grillo C, Blanck TJ, et al.: Nanomolar melatonin enhances nNOS expression and controls HaCaT-cells bioenergetics. IUBMB Life. 2012, 64:251-8.
[425]Masci A, Mastronicola D, Arese M, Piane M, De Amicis A, Blanck TJ, et al.: Control of cell respiration by nitric oxide in Ataxia Telangiectasia lymphoblastoid cells. Biochim Biophys Acta. 2008, 1777:66-73.
[426]Lira VA, Brown DL, Lira AK, Kavazis AN, Soltow QA, Zeanah EH, et al.: Nitric oxide and AMPK cooperatively regulate PGC-1 in skeletal muscle cells. J Physiol. 2010, 588:3551-66.
[427]McConell GK, Ng GP, Phillips M, Ruan Z, Macaulay SL, Wadley GD: Central role of nitric oxide synthase in AICAR and caffeine-induced mitochondrial biogenesis in L6 myocytes. J Appl Physiol (1985) 2010, 108:589-95.
[428]Nisoli E, Falcone S, Tonello C, Cozzi V, Palomba L, Fiorani M, et al.: Mitochondrial biogenesis by NO yields functionally active mitochondria in mammals. Proc Natl Acad Sci U S A. 2004, 101:16507-12.
[429]Remels AH, Gosker HR, Schrauwen P, Hommelberg PP, Sliwinski P, Polkey M, et al.: TNF-alpha impairs regulation of muscle oxidative phenotype: implications for cachexia? FASEB J. 2010, 24:5052-62.
[430]Palomer X, Alvarez-Guardia D, Rodríguez-Calvo R, Coll T, Laguna JC, Davidson MM, et al.: TNF-alpha reduces PGC-1alpha expression through NF-kappaB and p38 MAPK leading to increased glucose oxidation in a human cardiac cell model. Cardiovasc Res. 2009, 81:703-12.
[431]Beckman JS, Koppenol WH: Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. Am J Physiol. 1996, 271:C1424-37.
[432]Denicola A, Souza JM, Radi R: Diffusion of peroxynitrite across erythrocyte membranes. Proc Natl Acad Sci U S A. 1998, 95:3566-71.
[433]Radi R, Beckman JS, Bush KM, Freeman BA: Peroxynitrite oxidation of sulfhydryls. The cytotoxic potential of superoxide and nitric oxide. J Biol Chem 1991, 266:4244-50.
[434]MacMillan-Crow LA, Thompson JA: Tyrosine modifications and inactivation of active site manganese superoxide dismutase mutant (Y34F) by peroxynitrite. Arch Biochem Biophys. 1999, 366:82-8.
[435]Jang B, Han S: Biochemical properties of cytochrome c nitrated by peroxynitrite. Biochimie. 2006, 88:53-8.
[436]Batthyány C, Souza JM, Durán R, Cassina A, Cerveñansky C, Radi R: Time course and site(s) of cytochrome c tyrosine nitration by peroxynitrite. Biochemistry. 2005, 44:8038-46.
[437]Radi R, Rodriguez M, Castro L, Telleri R: Inhibition of mitochondrial electron transport by peroxynitrite. Arch Biochem Biophys. 1994, 308:89-95.
[438]Riobó NA, Clementi E, Melani M, Boveris A, Cadenas E, Moncada S, et al.: Nitric oxide inhibits mitochondrial NADH:ubiquinone reductase activity through peroxynitrite formation. Biochem J. 2001, 359:139-45.
[439]Boczkowski J, Lisdero CL, Lanone S, Carreras MC, Aubier M, Poderoso JJ: Peroxynitrite-mediated mitochondrial dysfunction. Biol Signals Recept. 2001, 10:66-80.
[440]Ischiropoulos H, Zhu L, Chen J, Tsai M, Martin JC, Smith CD, et al.: Peroxynitrite-mediated tyrosine nitration catalyzed by superoxide dismutase. Arch Biochem Biophys. 1992, 298:431-7.
[441]Aykaç-Toker G, Bulgurcuoğlu S, Koçak-Toker N: Effect of peroxynitrite on glutaredoxin. Hum Exp Toxicol. 2001, 20:373-6.
[442]Trujillo M, Folkes L, Bartesaghi S, Kalyanaraman B, Wardman P, Radi R: Peroxynitrite-derived carbonate and nitrogen dioxide radicals readily react with lipoic and dihydrolipoic acid. Free Radic Biol Med. 2005, 39:279-88.
[443]Cuzzocrea S, Zingarelli B, O’Connor M, Salzman AL, Szabó C: Effect of L-buthionine-(S, R)-sulphoximine, an inhibitor of gamma-glutamylcysteine synthetase on peroxynitrite- and endotoxic shock-induced vascular failure. Br J Pharmacol. 1998, 123:525-37.
[444]Arteel GE, Briviba K, Sies H: Protection against peroxynitrite. FEBS Lett. 1999, 445:226-30.
[445]Cuzzocrea S, Costantino G, Mazzon E, Caputi AP: Protective effect of N-acetylcysteine on multiple organ failure induced by zymosan in the rat. Crit Care Med. 1999, 27:1524-32.
[446]Buchczyk DP, Grune T, Sies H, Klotz LO: Modifications of glyceraldehyde-3-phosphate dehydrogenase induced by increasing concentrations of peroxynitrite: early recognition by 20S proteasome. Biol Chem. 2003, 384:237-41.
[447]Souza JM, Radi R: Glyceraldehyde-3-phosphate dehydrogenase inactivation by peroxynitrite. Arch Biochem Biophys. 1998, 360:187-94.
[448]Konorev EA, Hogg N, Kalyanaraman B: Rapid and irreversible inhibition of creatine kinase by peroxynitrite. FEBS Lett. 1998, 427:171-4.
[449]Bolaños JP, Heales SJ, Land JM, Clark JB: Effect of peroxynitrite on the mitochondrial respiratory chain: differential susceptibility of neurones and astrocytes in primary culture. J Neurochem. 1995, 64:1965-72.
[450]Pearce LL, Kanai AJ, Epperly MW, Peterson J: Nitrosative stress results in irreversible inhibition of purified mitochondrial complexes I and III without modification of cofactors. Nitric Oxide. 2005, 13:254-63.
[451]Radi R, Cassina A, Hodara R: Nitric oxide and peroxynitrite interactions with mitochondria. Biol Chem. 2002, 383:401-9.
[452]Radi R, Cassina A, Hodara R, Quijano C, Castro L: Peroxynitrite reactions and formation in mitochondria. Free Radic Biol Med. 2002, 33:1451-64.
[453]Cassina AM, Hodara R, Souza JM, Thomson L, Castro L, Ischiropoulos H, et al.: Cytochrome c nitration by peroxynitrite. J Biol Chem. 2000, 275:21409-15.
[454]Han D, Canali R, Garcia J, Aguilera R, Gallaher TK, Cadenas E: Sites and mechanisms of aconitase inactivation by peroxynitrite: modulation by citrate and glutathione. Biochemistry. 2005, 44:11986-96.
[455]Castro L, Rodriguez M, Radi R: Aconitase is readily inactivated by peroxynitrite, but not by its precursor, nitric oxide. J Biol Chem. 1994, 269:29409-15.
[456]Forsmark-Andrée P, Persson B, Radi R, Dallner G, Ernster L: Oxidative modification of nicotinamide nucleotide transhydrogenase in submitochondrial particles: effect of endogenous ubiquinol. Arch Biochem Biophys. 1996, 336:113-20.
[457]Vieira HL, Belzacq AS, Haouzi D, Bernassola F, Cohen I, Jacotot E, et al.: The adenine nucleotide translocator: a target of nitric oxide, peroxynitrite, and 4-hydroxynonenal. Oncogene. 2001, 20:4305-16.
[458]Scarlett JL, Packer MA, Porteous CM, Murphy MP: Alterations to glutathione and nicotinamide nucleotides during the mitochondrial permeability transition induced by peroxynitrite. Biochem Pharmacol. 1996, 52:1047-55.
[459]Paixão J, Dinis TC, Almeida LM: Protective role of malvidin-3-glucoside on peroxynitrite-induced damage in endothelial cells by counteracting reactive species formation and apoptotic mitochondrial pathway. Oxid Med Cell Longev. 2012, 2012:428538.
[460]Sharpe MA, Cooper CE: Interaction of peroxynitrite with mitochondrial cytochrome oxidase. Catalytic production of nitric oxide and irreversible inhibition of enzyme activity. J Biol Chem 1998, 273:30961-72.
[461]Le Bras M, Clément MV, Pervaiz S, Brenner C: Reactive oxygen species and the mitochondrial signaling pathway of cell death. Histol Histopathol. 2005, 20:205-19.
[462]Szabó C, Zingarelli B, O’Connor M, Salzman AL: DNA strand breakage, activation of poly (ADP-ribose) synthetase, and cellular energy depletion are involved in the cytotoxicity of macrophages and smooth muscle cells exposed to peroxynitrite. Proc Natl Acad Sci U S A. 1996, 93:1753-8.
[463]Pacher P, Beckman JS, Liaudet L: Nitric oxide and peroxynitrite in health and disease. Physiol Rev. 2007, 87:315-424.
[464]Liaudet L, Szabó G, Szabó C: Oxidative stress and regional ischemia-reperfusion injury: the peroxynitrite-poly(ADP-ribose) polymerase connection. Coron Artery Dis. 2003, 14:115-22.
[465]Szabó C: Multiple pathways of peroxynitrite cytotoxicity. Toxicol Lett. 2003, 140–141:105-12.
[466]Liaudet L: Poly(adenosine 5’-diphosphate) ribose polymerase activation as a cause of metabolic dysfunction in critical illness. Curr Opin Clin Nutr Metab Care. 2002, 5:175-84.
[467]Liaudet L, Oddo M: Role of poly(adenosine diphosphate-ribose) polymerase 1 in septic peritonitis. Curr Opin Crit Care. 2003, 9:152-8.
[468]Ha HC, Snyder SH: Poly(ADP-ribose) polymerase is a mediator of necrotic cell death by ATP depletion. Proc Natl Acad Sci U S A. 1999, 96:13978-82.
[469]Hainaut P, Milner J: Redox modulation of p53 conformation and sequence-specific DNA binding in vitro. Cancer Res. 1993, 53:4469-73.
[470]Buizza L, Cenini G, Lanni C, Ferrari-Toninelli G, Prandelli C, Govoni S, et al.: Conformational altered p53 as an early marker of oxidative stress in Alzheimer’s disease. PLoS One. 2012, 7:e29789.
[471]Buizza L, Prandelli C, Bonini SA, Delbarba A, Cenini G, Lanni C, et al.: Conformational altered p53 affects neuronal function: relevance for the response to toxic insult and growth-associated protein 43 expression. Cell Death Dis. 2013, 4:e484.
[472]Cobbs CS, Whisenhunt TR, Wesemann DR, Harkins LE, Van Meir EG, Samanta M: Inactivation of wild-type p53 protein function by reactive oxygen and nitrogen species in malignant glioma cells. Cancer Res. 2003, 63:8670-3.
[473]Olovnikov IA, Kravchenko JE, Chumakov PM: Homeostatic functions of the p53 tumor suppressor: regulation of energy metabolism and antioxidant defense. Semin Cancer Biol. 2009, 19:32-41.
[474]Ma W, Sung HJ, Park JY, Matoba S, Hwang PM: A pivotal role for p53: balancing aerobic respiration and glycolysis. J Bioenerg Biomembr. 2007, 39:243-6.
[475]Bensaad K, Vousden KH: p53: new roles in metabolism. Trends Cell Biol. 2007, 17:286-91.
[476]Mauro C, Leow SC, Anso E, Rocha S, Thotakura AK, Tornatore L, et al.: NF-κB controls energy homeostasis and metabolic adaptation by upregulating mitochondrial respiration. Nat Cell Biol. 2011, 13:1272-9.
[477]Johnson RF, Witzel II, Perkins ND: p53-dependent regulation of mitochondrial energy production by the RelA subunit of NF-κB. Cancer Res. 2011, 71:5588-97.
[478]Assaily W, Benchimol S: Differential utilization of two ATP-generating pathways is regulated by p53. Cancer Cell. 2006, 10:4-6.
[479]Park JY, Wang PY, Matsumoto T, Sung HJ, Ma W, Choi JW, et al.: p53 improves aerobic exercise capacity and augments skeletal muscle mitochondrial DNA content. Circ Res. 2009, 105:705-12.
[480]Winklhofer KF, Haass C: Mitochondrial dysfunction in Parkinson’s disease. Biochim Biophys Acta. 2010, 1802:29-44.
[481]Fink M: Cytopathic hypoxia in sepsis. Acta Anaesthesiol Scand Suppl. 1997, 110:87-95.
[482]L’Her E, Sebert P: A global approach to energy metabolism in an experimental model of sepsis. Am J Respir Crit Care Med. 2001, 164:1444-7.
[483]Fink MP: Cytopathic hypoxia. Mitochondrial dysfunction as mechanism contributing to organ dysfunction in sepsis. Crit Care Clin 2001, 17:219-37.
[484]Xie YW, Wolin MS: Role of nitric oxide and its interaction with superoxide in the suppression of cardiac muscle mitochondrial respiration. Involvement in response to hypoxia/reoxygenation. Circulation. 1996, 94:2580-6.
[485]Schweizer M, Richter C: Nitric oxide potently and reversibly deenergizes mitochondria at low oxygen tension. Biochem Biophys Res Commun. 1994, 204:169-75.
[486]Mariappan N, Elks CM, Fink B, Francis J: TNF-induced mitochondrial damage: a link between mitochondrial complex I activity and left ventricular dysfunction. Free Radic Biol Med. 2009, 46:462-70.
[487]Goossens V, Stangé G, Moens K, Pipeleers D, Grooten J: Regulation of tumor necrosis factor-induced, mitochondria- and reactive oxygen species-dependent cell death by the electron flux through the electron transport chain complex I. Antioxid Redox Signal. 1999, 1:285-95.
[488]Moe GW, Marin-Garcia J, Konig A, Goldenthal M, Lu X, Feng Q: In vivo TNF-alpha inhibition ameliorates cardiac mitochondrial dysfunction, oxidative stress, and apoptosis in experimental heart failure. Am J Physiol Heart Circ Physiol. 2004, 287:H1813-20.
[489]Schulze-Osthoff K, Bakker AC, Vanhaesebroeck B, Beyaert R, Jacob WA, Fiers W: Cytotoxic activity of tumor necrosis factor is mediated by early damage of mitochondrial functions. Evidence for the involvement of mitochondrial radical generation. J Biol Chem 1992, 267:5317-23.
[490]Vaughan RA, Garcia-Smith R, Trujillo KA, Bisoffi M: Tumor necrosis factor alpha increases aerobic glycolysis and reduces oxidative metabolism in prostate epithelial cells. Prostate. 2013, 73:1538-46.
[491]Vaughan RA, Garcia-Smith R, Dorsey J, Griffith JK, Bisoffi M, Trujillo KA: Tumor necrosis factor alpha induces Warburg-like metabolism and is reversed by anti-inflammatory curcumin in breast epithelial cells. Int J Cancer. 2013, 133:2504-10.
[492]Samavati L, Lee I, Mathes I, Lottspeich F, Hüttemann M: Tumor necrosis factor alpha inhibits oxidative phosphorylation through tyrosine phosphorylation at subunit I of cytochrome c oxidase. J Biol Chem. 2008, 283:21134-44.
[493]Jia L, Kelsey SM, Grahn MF, Jiang XR, Newland AC: Increased activity and sensitivity of mitochondrial respiratory enzymes to tumor necrosis factor alpha-mediated inhibition is associated with increased cytotoxicity in drug-resistant leukemic cell lines. Blood. 1996, 87:2401-10.
[494]Gottlieb E, Vander Heiden MG, Thompson CB: Bcl-x(L) prevents the initial decrease in mitochondrial membrane potential and subsequent reactive oxygen species production during tumor necrosis factor alpha-induced apoptosis. Mol Cell Biol. 2000, 20:5680-9.
[495]Li C, Liu Q, Li N, Chen W, Wang L, Wang Y, et al.: EAPF/Phafin-2, a novel endoplasmic reticulum-associated protein, facilitates TNF-alpha-triggered cellular apoptosis through endoplasmic reticulum-mitochondrial apoptotic pathway. J Mol Med (Berl). 2008, 86:471-84.
[496]Uslu R, Bonavida B: Involvement of the mitochondrion respiratory chain in the synergy achieved by treatment of human ovarian carcinoma cell lines with both tumor necrosis factor-alpha and cis-diamminedichloroplatinum. Cancer. 1996, 77:725-32.
[497]Hennet T, Richter C, Peterhans E: Tumour necrosis factor-alpha induces superoxide anion generation in mitochondria of L929 cells. Biochem J. 1993, 289:587-92.
[498]Zell R, Geck P, Werdan K, Boekstegers P: TNF-alpha and IL-1 alpha inhibit both pyruvate dehydrogenase activity and mitochondrial function in cardiomyocytes: evidence for primary impairment of mitochondrial function. Mol Cell Biochem. 1997, 177:61-7.
[499]Tredget EE, Yu YM, Zhong S, Burini R, Okusawa S, Gelfand JA, et al.: Role of interleukin 1 and tumor necrosis factor on energy metabolism in rabbits. Am J Physiol. 1988, 255:E760-8.

BMC Medicine
The many roads to mitochondrial dysfunction in neuroimmune and neuropsychiatric disorders

Michael Berk² Gerwyn Morris¹
[1] Tir Na Nog, Bryn Road seaside 87, Llanelli, Cardiff SA152LW, Wales, UK;Department of Psychiatry, University of Melbourne, Level 1 North, Main Block, Royal Melbourne Hospital, Parkville 3052, Australia
关键词: Neurology; Psychiatry; Peroxynitrite; Parkinson’s disease; Oxidative stress; Nitric oxide; Multiple sclerosis; Mitochondrial dysfunction; Inflammatory; Immune dysfunction; Depression; Cytokines; Chronic fatigue syndrome; Schizophrenia; Bipolar disorder; Autism;
Others : 1160637 DOI : 10.1186/s12916-015-0310-y

received in 2014-12-23, accepted in 2015-03-04, 发布年份 2015
PDF


	文献评价指标
	下载次数：31次	浏览次数：73次

【 摘 要 】

Background

Discussion

Summary

【 授权许可】

【 预 览 】

【 图 表 】

【 参考文献 】

【摘要】

【授权许可】

【预览】

【图表】

【参考文献】