Lipids in Health and Disease | |
Lipid mediators in plasma of autism spectrum disorders | |
Laila Al-Ayadhi1  Afaf El-Ansary1  | |
[1] Shaik AL-Amodi Autism Research Chair, King Saud University, Riyadh, Saudi Arabia | |
关键词: Arachidonic acid; Isoprostane; Leukotrienes; Prostaglandins; Inflammation; Autism; | |
Others : 1160138 DOI : 10.1186/1476-511X-11-160 |
|
received in 2012-06-06, accepted in 2012-10-26, 发布年份 2012 | |
【 摘 要 】
Background
Inflammation is increasingly recognized as being of both physiological and pathological importance in the immature brain. Cerebellar pathology occurs in autism, as a neurodevelopmental disorder with genetic and environmental origins. The genesis of this disorder is still not understood but inflammation in utero or early in childhood is an environmental risk factor.
Methods
Prostaglandin E2 (PGE2), cysteinyl leukotriene as two important lipid mediators together with 8 isoprostane as marker of oxidative stress were measured using ELISA in plasma of 20 male autistic patients compared to 19 age and gender matching control participants.
Results
PGE2, leukotrienes and isoprostanes recorded significantly elevated levels in autistics compared to controls. Role of these measured parameters in inflammation and autoimmunity as two etiological factors in autism were discussed in details.
Conclusion
Receiver Operating Characteristic (ROC) curve analysis shows satisfactory values of area under the curve (AUC) which could reflect the high degree of specificity and sensitivity of the altered PGE2, leukotrienes and isoprostanes as predictive biomarkers in autistic patients from Saudi Arabia.
【 授权许可】
2012 El-Ansary and Al-Ayadhi; licensee BioMed Central Ltd.
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
20150410094522785.pdf | 968KB | download | |
Figure 6. | 112KB | Image | download |
Figure 5. | 94KB | Image | download |
Figure 4. | 41KB | Image | download |
Figure 3. | 42KB | Image | download |
Figure 2. | 40KB | Image | download |
Figure 1. | 53KB | Image | download |
【 图 表 】
Figure 1.
Figure 2.
Figure 3.
Figure 4.
Figure 5.
Figure 6.
【 参考文献 】
- [1]Centers for Disease Control and Prevention (CDC): Prevalence of autism spectrum disorders - Autism and Developmental Disabilities Monitoring Network, United States, 2006. MMWR Surveill Summ 2009, 58(10):1-20.
- [2]Ozonoff S, Iosif AM, Baguio F, et al.: A prospective study of the emergence of early behavioral signs of autism. J Am Acad Child Adolesc Psychiatry 2010, 49(3):256-266.
- [3]Ozonoff S, Heung K, Byrd R, Hansen R, Hertz-Picciotto I: The onset of autism: patterns of symptom emergence in the first years of life. Autism Res 2008, 1(6):320-328.
- [4]Hussain J, Woolf AD, Sandel M, Shannon MW: Environmental evaluation of a child with developmental disability. Pediatr Clin North Am 2007, 54(1):47-62.
- [5]Kalkbrenner AE, Daniels JL, Chen JC, Poole C, Emch M, Morrissey J: Perinatal exposure to hazardous air pollutants and autism spectrum disorders at age 8. Epidemiology 2010, 21(5):631-641.
- [6]Lintas C, Sacco R, Persico AM: Genome-wide expression studies in autism spectrum disorder, Rett syndrome, and Down syndrome. Neurobiol Dis 2012, 45(1):57-68.
- [7]El-Ansary AK, Ben Bacha AG, Al-Ayadhi LY: Proinflammatory and proapoptotic markers in relation to mono and di-cations in plasma of autistic patients from Saudi Arabia. J Neuroinflammation 2011, 8:142. BioMed Central Full Text
- [8]El-Ansary AK, Ben Bacha AG, Al-Ayadhi LY: Relationship between chronic lead toxicity and plasma neurotransmitters in autistic patients from Saudi Arabia. Clin Biochem 2011, 44(13):1116-1120.
- [9]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.
- [10]Schuhmann MU, Mokhtarzadeh M, Stichtenoth DO, et al.: Temporal profiles of cerebrospinal fluid leukotrienes, brain edema and inflammatory response following experimental brain injury. Neurol Res 2003, 25(5):481-491.
- [11]Black KL, Hoff JT: Leukotrienes Increase Blood–brain Barrier Permeability Following Intraparenchymal Injections in Rats. Ann Neurol 1985, 18(3):349-351.
- [12]Sang N, Chen C: Lipid signaling and synaptic plasticity. Neuroscientist 2006, 12(5):425-434.
- [13]Chen C, Bazan NG: Lipid signaling: sleep, synaptic plasticity and neuroprotection. Prostaglandins Other Lipid Mediat 2005, 77(1–4):65-76.
- [14]Hein AM, O’Banion MK: Neuroinflammation and memory: the role of prostaglandins. Mol Neurobiol 2009, 40(1):15-32.
- [15]Leger DF, et al.: Prostaglandins E2 at new glance: Novel insights in functional diversity offer therapeutic chances. Int J Biochem Cell Biol 2010, 42(2):198-201.
- [16]Roberts LJ, Morrow JD: Measurement of F2-isoprostanes as an index of oxidative stress in vivo. Free Radic Biol Med 2000, 28:505-513.
- [17]Narumiya S, Ogorochi T, Nakao K, Hayaishi O: Prostaglandin D2 in the rat brain, spinal cord and the pituitary: basal level and regional distribution. Life Science 1982, 31:2093-2103.
- [18]Brus R, Herman ZS, Szkilnik R, Zabawska J: Mediation of central prostaglandin effects by serotoninergic neurons. Psychopharmacology 1979, 64:116-120.
- [19]Saito R, Kamiya H, Ono N: Role of central muscarinic receptor of prostaglandin I2 in cardiovascular function in rat. Brain Res 1985, 330:167-169.
- [20]Naidu PS, Kulkarni SK: Differential effects of cyclooxygenase inhibitors on haloperidolinduced catalepsy. Prog Neuropsychopharmacol Biol Psychiatry 2002, 26:819-822.
- [21]Morrow JD, Hill KE, Burk RF, Nammour TM, Badr KF, Roberts LJ 2nd: A series of prostaglandin F2-like compounds are produced in vivo in humans by anon-cyclooxygenase, free radical-catalyzed mechanism. Proc Natl Acad Sci USA 1990, 87(23):9383-9387.
- [22]Hardy ARP, Chemtob S, Detbarn WD, Morrow JD: Formation of isoprostane-like compounds (neuroprostanes) in vivo from docosahexaenoic acid. J Biol Chem 1998, 273:13605-13612.
- [23]Ito S, Okuda-Ashitaka E, Minami T: Central and peripheral roles of prostaglandins in pain and their interactions with novel neuropeptides nociceptin and nocistatin. Neurosci Res 2001, 41(4):299-332.
- [24]Tamiji J, Crawford DA: The neurobiology of lipid metabolism in autism spectrum disorders. Neurosignals 2010, 18(2):98-112.
- [25]El-Ansary AK, Bacha AG, Al-Ayahdi LY: Impaired plasma phospholipids and relative amounts of essential polyunsaturated fatty acids in autistic patients from Saudi Arabia. Lipids Health Dis 2011, 22:10-63.
- [26]Pepe MS, Feng Z, Huang Y, et al.: Integrating the predictiveness of a marker with its performance as a classifier. Am J Epidemiol 2008, 167(3):362-368.
- [27]Evans TA, Siedlak SA, Lu L, et al.: The autistic phenotype exhibits a remarkably localized modification of brain protein by products of free radical-induced lipid oxidation. Am J Biochem Biotechnol 2008, 4:61-72.
- [28]Salomon RG, Subbanagounder G, Singh U, O’Neil J, Hoff HF: Oxidation of low-density lipoproteins produces levuglandin-protein adducts. Chem Res Toxicol 1997, 10(7):750-759.
- [29]Boutaud O, Brame CJ, Salomon RG, Roberts LJ 2nd, Oates JA: Characterization of the lysyl adducts formed from prostaglandin H2 via the levuglandin pathway. Biochemistry 1999, 38(29):9389-9396.
- [30]Murthi KK, Friedman LR, Oleinick NL, Salomon RG: Formation of DNA-protein cross-links in mammalian cells by levuglandin E2. Biochemistry 1993, 32(15):4090-4097.
- [31]Salomon RG: Levuglandins and isolevuglandins: stealthy toxins of oxidative injury. Antioxid. Redox. Signal 2005, 7(1–2):185-201.
- [32]Ming X, Stein TP, Brimacombe M, Johnson WG, Lambert GH, Wagner GC: Increased excretion of lipid peroxidation biomarker in autism. Prostaglandins Leukot Essent Fatty Acids 2005, 73(5):379-384.
- [33]El-Ansary A, Ben Bacha AG, Al-Ayahdi LY: Plasma fatty acids as diagnostic markers in autistic patients from Saudi Arabia. Lipids Health Dis 2011, 10:62. BioMed Central Full Text
- [34]Wiest MM, German JB, Harvey DJ, Watkins SM, Hertz-Picciotto I: Plasma fatty acid profiles in autism: a case–control study. Prostaglandins Leukot Essent Fatty Acids 2009, 80(4):221-227.
- [35]Lu L: Clinical and animal studies of lipid-derived protein modifications in autism, kidney dialysis, keratitis and age-related macular degeneration. PhD thesis, Department of Chemistry Department. Case Western Researve University; 2007.
- [36]Singh VK: Phenotypic expression of autoimmune autistic disorder (AAD): a major subset of autism. Ann Clin Psychiatry 2009, 21(3):148-161.
- [37]Connolly AM, Chez MG, Pestronk A, Arnold ST, Mehta S, Deuel RK: Serum autoantibodies to brain in Landau-Kleffner variant, autism, and other neurologic disorders. J Pediatr 1999, 134:607-613.
- [38]Vojdani A, Campbell AW, Anyanwu E, Kashanian A, Bock K, Vojdani E: Antibodies to neuron-specific antigens in children with autism: possible cross-reaction with encephalitogenic proteins from milk, Chlamydia pneumoniae and Streptococcus group A. J Neuroimmunol 2002, 129(1–2):168-177.
- [39]Steinke JW, Kennedy JL: Leukotriene Inhibitors in Sinusitis. Curr Infect Dis Rep 2012. In press
- [40]Wu Y, He C, Gao Y, He S, Liu Y, Lai L: Dynamic modeling of human 5-lipoxygenase-inhibitor interactions helps to discover novel inhibitors. J Med Chem 2012, 55(6):2597-2605.
- [41]Muskiet FAJ: Pathophysiology and Evolutionary Aspects of Dietary Fats and Long-Chain Polyunsaturated Fatty Acids across the Life Cycle. In Fat Detection: Taste, Texture, and Post Ingestive Effects. Boca Raton (FL). Edited by Montmayeur JP, Le C. CRC Press; 2010. Chapter 2. Frontiers in Neuroscience
- [42]Abu Shmais GA, Al-Aydhi L, Al-Dbass A, El-Ansary A: Mechanism of nitrogen metabolism-related parameters and enzyme activities in the pathophysiology of autism. J Neurodev Disord 2012. BioMed Central Full Text
- [43]Baron-Cohen S, Ring R, et al.: The amygdale theory of autism. Neurosci Biobehav Rev 2000, 24(3):355-364.
- [44]Lozinsky S: Misoprostol elevates intracellular calcium levels and increases glutamate release in type-I astrocytes: Implication in autism. Toronto Ontario: York University; 2010. [Master thesis]
- [45]Libbey JE, Sweeten TL, McMahon WM, Fujinami RS: Autistic disorder and viral infections. J Neurovirol 2005, 11(1):1-10.
- [46]Manzardo AM, Henkhaus R, Dhillon S, Butler MG: Plasma cytokine levels in children with autistic disorder and unrelated siblings. Int J Dev Neurosci 2012, 30(2):121-127.
- [47]Wei H, Chadman KK, McCloskey DP, Sheikh AM, Malik M, Brown WT, Li X: Brain IL-6 elevation causes neuronal circuitry imbalances and mediates autism-like behaviors. Biochim Biophys Acta 2012, 1822(6):831-842.
- [48]Wei H, Zou H, Sheikh AM, Malik M, Dobkin C, Brown WT, Li X: IL-6 is increased in the cerebellum of autistic brain and alters neural cell adhesion, migration and synaptic formation. J Neuroinflammation 2011, 8:52. BioMed Central Full Text
- [49]Auyeung B, Baron-Cohen S, Ashwin E, Knickmeyer R, Taylor K, Hackett G: Fetal testosterone and autistic traits. Brit J Psychol (London, England 1953, 100(1):1-22.
- [50]James WH: Further evidence that some male-based neurodevelopmental disorders are associated with high intrauterine testosterone concentrations. Dev Med Child Neurol 2008, 50(1):15-18.
- [51]Geier D, Geier M: A clinical trial of combined anti-androgenand anti-heavy metal therapy in autistic disorders. Neuro Endocrinol Lett 2006, 27(6):833-838.
- [52]Geier D, Geier M: A prospective assessment of androgen levels in patients with autistic spectrum disorders: biochemical underpinnings and suggested therapies. Neuro Endocrinol Lett 2007, 28(5):565-573.
- [53]Tordjman S, Ferrari P, Sulmont V, Duyme M, Roubertoux P: Androgenic activity in autism. Am J Psychiatry 1997, 154:1626-1627.
- [54]Dean S: Regulation of cerebellar estradiol synthesis and Purkinje cell morphology by prostaglandins: Implications for neurodevelopmental disease. Baltimore: University of Maryland; 2009.
- [55]Rangel-Huerta OD, Aguilera CM, Mesa MD, Gil A: Omega-3 long-chain polyunsaturated fatty acids supplementation on inflammatory biomakers: a systematic review of randomised clinical trials. Br J Nutr 2012, 107(2):S159-S170.