期刊论文详细信息
Lipids in Health and Disease
On the protective effect of omega-3 against propionic acid-induced neurotoxicity in rat pups
Amina R El-Gezeery1  Sooad K Al-Daihan1  Afaf K El-Ansary1 
[1] Biochemistry Department, Science College, King Saud University, P.O box 22452, zip code 11495, Riydh, Saudi Arabia
关键词: Autism;    Phospholipids;    Cytokines;    Caspase-3;    Neurotransmitters;    Omega-3;    Propionic acid;   
Others  :  1212548
DOI  :  10.1186/1476-511X-10-142
 received in 2011-06-05, accepted in 2011-08-19,  发布年份 2011
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【 摘 要 】

Backgrounds

The investigation of the environmental contribution for developmental neurotoxicity is very important. Many environmental chemical exposures are now thought to contribute to the development of neurological disorders, especially in children. Results from animal studies may guide investigations of human populations toward identifying environmental contaminants and drugs that produce or protect from neurotoxicity and may help in the treatment of neurodevelopmental disorders.

Objective

To study the protective effects of omega-3 polyunsaturated fatty acid on brain intoxication induced by propionic acid (PPA) in rats.

Methods

24 young male Western Albino rats were enrolled in the present study. They were grouped into three equal groups; oral buffered PPA-treated group given a nuerotoxic dose of 250 mg/Kg body weight/day for 3 days; omega-3 - protected group given a dose of 100 mg/kg body weight/day omega-3 orally daily for 5 days followed by PPA for 3 days, and a third group as control given only phosphate buffered saline. Tumor necrosis factor-α, caspase-3, interlukin-6, gamma amino-buteric acid (GABA), serotonin, dopamine and phospholipids were then assayed in the rats brain's tissue of different groups.

Results

The obtained data showed that PPA caused multiple signs of brain toxicity as measured by depletion of gamaaminobyteric acid (GABA), serotonin (5HT) and dopamine (DA) as three important neurotransmitters that reflect brain function. A high significant increase of interlukin-6 (Il-6), tumor necrosis factor-α (TNF-α) as excellent markers of proinflammation and caspase-3 as a proapotic marker were remarkably elevated in the intoxicated group of rats. Moreover, brain phospholipid profile was impaired in PPA-treated young rats recording lower levels of phosphatidylethanolamine (PE), phosphatidylserine (PS) and phosphatidylcholine (PC).

Conclusions

Omega-3 fatty acids showed a protective effects on PPA - induced changes in rats as there was a remarkable amelioration of most of the measured parameters (i.e. higher GABA, 5HT, DA, PE, PS and PC) and lower Il-6, TNF-α and caspase-3.

【 授权许可】

   
2011 El-Ansary et al; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Connors SL, Levitt P, Matthews SG, Slotkin TA, Johnston MV, Kinney HC, Johnson WG, Dailey RM, Zimmerman AW: Fetal mechanisms in neurodevelopmental disorders. Pediatr Neurol 2008, 38:163-176.
  • [2]Slotkin TA: Cholinergic systems in brain development and disruption by neurotoxicants: nicotine, environmental tobacco smoke, organophosphates. Toxicology and Applied Pharmacology 2004, 198(2):132-151.
  • [3]Vancassel S, Durand G, Barthélémy C, Lejeune B, Martineau J, Guilloteau D, Andrès C, Chalon S: Plasma fatty acid levels in autistic children. Prostaglandins Leukot Essent Fatty Acids 2001, 65(1):1-7.
  • [4]Horrobin DF: Schizophrenia: the illness that made us human. Med Hypotheses 1998, 50(4):269-88.
  • [5]Bourre JM: Dietary omega-3 fatty acids for women. Biomed Pharmacother 2007, 61(2-3):105-12.
  • [6]Gupta R: Deshpande: SB3-Nitropropionic acid depresses spinal reflexes involving GABAergic and glycinergic transmission in neonatal rat spinal cord in vitro. Life Sci 2008, 83(21-22):756-60.
  • [7]Cannizzaro C, Monastero R, Vacca M, Martire M: [3H]-DA release evoked by low pH medium and internal H+ accumulation in rat hypothalamic synaptosomes: involvement of calcium ions. Neurochem Int 2003, 43:9-17.
  • [8]Severson CA, Wang W, Pieribone VA, Dohle CI, Richerson GB: Mid brain serotonergic receptors neurons are central pH chemoreceptors. Nat Neurosci 2003, 6:1139-40.
  • [9]Roe CR, Millington DS, Maltby DA, Bohan TP, Hoppel CL: l-Carnitine enhances excretion ofpropionyl coenzymeA as propionyl carnitine in propionic acidemia. J Cli Invest 1984, 73:1785-8.
  • [10]Wajne M, Latin A, Wyse AT, Dutra-Filho CS: The role of oxidative damage in the neuropathology of organic acidurias: insights from animal studies. J Inherit Metab Dis 2004, 27:427-48.
  • [11]James SJ, Rose S, Melnyk S, Jernigan S, Blossom S, Pavliv O, et al.: Cellular and mitochondrial glutathione redox imbalance in lymphoblastoid cells derived from children with autism. FASEBJ 2009, 23:2374-83.
  • [12]Filipek PA, Jurane kJ, Nguyen MT, Cummings C, Gargus JJ: Relative carnitine deficiency in autism. J Autism Dev Disord 2004, 34:615-23.
  • [13]Macfabe DF, Cain NE, Boond F, Ossenkopp KP, Cain DP: Effects of the enteric bacterial metabolic product propionic acid on object-directed behavior, social behavior, cognition, and neuroinflammation in adolescent rats: Relevance to autism spectrum disorder. Behavioural Brain Research 2011, 217(1-2):47-54.
  • [14]Julien C, Berthiaume L, Hadj-Taha A, Rajput AH, Bedard PJ, Di Paolo T, Julien P, Calon F: Postmortem brain fatty acid profile of levodopa-treated Parkinson disease patients and parkinsonian monkeys. Neurochem Int 2006, 48:404-414.
  • [15]Salem N Jr, Litman B, Kim HY, Gawrisch K: Mechanisms of action of docosahexaenoic acid in the nervous system. Lipids 2001, 36:945-960.
  • [16]Galli C, Marangoni F, Galella G: Modulation of lipid derived mediators by polyunsaturated fatty acids. Prostaglandins Leukot Essent Fatty Acids 1993, 48:51-55.
  • [17]Green JT, Orr SK, Bazinet RP: The emerging role of group VI calcium-independent phospholipase A2 in releasing docosahexaenoic acid from brain phospholipids. J Lipid Res 2008 49:939-944.
  • [18]Bazan NG: Neuroprotectin D1 (NPD1): a DHA-derived mediator that protects brain and retina against cell injury-induced oxidative stress. Brain Pathol 2005, 15:159-166.
  • [19]Marcheselli VL, Hong S, Lukiw WJ, Tian XH, Gronert K, Musto A, Hardy M, Gimenez JM, Chiang N, Serhan CN, Bazan NG: Novel docosanoids inhibit brain ischemia-reperfusion-mediated leukocyte infiltration and pro-inflammatory gene expression. J Biol Chem 2003, 278(44):43807-17.
  • [20]Calon F, Lim GP, Yang F, Morihara T, Teter B, Ubeda O, Rostaing P, Triller A, Salem N Jr, Ashe KH, Frautschy SA, Cole GM: Docosahexaenoic acid protects from dendritic pathology in an Alzheimer's disease mouse model. Neuron 2004, 43:633-645.
  • [21]Hashimoto S, Hossain T, Shimad K, Sugioka H, Yamasaki Y, Fujii Y, Ishibashi Y, Oka J, Shido O: Docosahexaenoic acid provides protection from impairment of learning ability in Alzheimer's disease model rats. J Neurochem 2002, 81:1084-1091.
  • [22]Calon F, Lim GP, Morihara T, Yang F, Ubeda O, Salem N, Frautschy SA, Cole GM: Dietary n-3 polyunsaturated fatty acid depletion activates caspases and decreases NMDA receptors in the brain of a transgenic mouse model of Alzheimer's disease. Eur J Neurosci 2005, 22:617-626.
  • [23]Wyatt I, Farnworth M, Gyte AJ, Lock EA: L-2-Chloropropionic acid metabolism and disposition in male rats: relevance to cerebellar injury. Arch Toxicol 1997, 71(11):668-76.
  • [24]Bligh EG, Dyer WJ: A rapid method of total lipid extraction and purification. Can J Biochem Physiol 1959, 37(8):911-7.
  • [25]MacFabe DF, Cain DP, Rodriguez-Capote K, Franklin AE, Hoffman JE, Boond F, Taylor AR, Kavaliers M, Ossenkopp KP: Neurobiological effects of intraventricular propionic acid in rats: Possible role of short chain fatty acids on the pathogenesis and characteristics of autism spectrum disorders. Behavioural Brain Research 2007, 176:149-169.
  • [26]Marszalek JR, Lodish HF: Docosahexaenoic acid, fatty acid-interacting proteins, and neuronal function: breastmilk and fish are good for you. Ann Rev Cell Dev Biol 2005, 21:633-657.
  • [27]Bourre JM: Roles of unsaturated fatty acids (especially omega-3 fatty acids) in the brain at various ages and during ageing. J Nutr 2004, 8:163-174.
  • [28]Martin RE, Bazan NG: Changing fatty acid content of growth cone lipids prior to synaptogenesis. J Neurochem 1992, 59:318-325.
  • [29]Moreira JD, Knorr L, Thomazi AP, Simaõ F, Battu C, Oses JP, Gottfried C, Wofchuk S, Salbego C, Souza DO, Perry MLS, Vinade L: Dietary Omega-3 fatty acids attenuate cellular damage after a hippocampal ischemic insult in adult rats. Jouranl of Nutrition Biochemistry 2010, 21(4):351-6.
  • [30]Zimmer L, Delion-Vancassel S, Durand G, Guilloteau D, Bodard S, Besnard JC, Chalon S: Modifications of dopamine neurotransmission in the nucleous accumbens of rats deficient in n-3 polyunsaturated fatty acids. J Lipid Res 2000, 41:32-40.
  • [31]Tzingounis AV, Wadiche JI: Glutamate transporters: confining runaway excitation by shaping synaptic transmission. Nat Rev Neurosci 2007, 8(12):935-947.
  • [32]Carrie I, Cle'ment M, de Javel D, France's H, Bourre JM: Phospholipid supplementation reverses behavioral and biochemical alterations inducedby n-3 polyunsaturated fatty acid deficiency in mice. J Lipid Res 2000, 41(3):473-480.
  • [33]Moriguchi T, Greiner RS, Salem N: Behavioral deficits associated with dietary induction of decreased brain docosahexaenoic acid concentration. J Neurochem 2000, 75(6):2563-2573.
  • [34]Takeuchi T, Iwanaga M, Harada E: Possible regulatory mechanism of DHA induced anti-stress reaction in rats. Brain Res 2003, 964(1):136-143.
  • [35]Lavialle M, Champeil-Potokar G, Alessandri JM, Balasse L, Guesnet P, Papillon C, Pe' vet P, Vancassel S, Vivien-Roels B, Denis I: An (n-3) polyunsaturated fatty acid-deficient diet disturbs daily locomotor activity, melatonin rhythm, and striatal dopamine in Syrian hamsters. J Nutr 2008, 138(9):1719-1724.
  • [36]Bourre JM: Dietary omega-3 Fatty acids and psychiatry: mood, behaviour, stress, depression, dementia and aging. J Nutr Health Aging 2005, 9(1):31-8.
  • [37]Anisman H: Cascading effects of stressors and inflammatory immune system activation: implications for major depressive disorder. J Psychiatry Neurosci 2009, 34:4-20.
  • [38]Hartwig S, Thöne J, Hovemann B, Gold R, Juckelc G, Linker RA, Perugaa I: Inflammation modulates anxiety in ananimal model of multiple sclerosis. Behavioural Brain Research 2011, 220:20-29.
  • [39]Suphioglu C, De Mel D, Kumar L, Sadli N, Freestone D, Michalczyk A, Sinclair A, Leigh Ackland M: The omega-3 fatty acid, DHA, decreases neuronal cell death in association with altered zinc transport. FEBS Letters 2010, 584:612-618.
  • [40]Akbar M, Calderon F, Wen Z, Kim HY: Docosahexaenoic acid: a positive modulator of Akt signaling in neuronal survival. Proc Natl Acad Sci USA 2005, 102:10858-10863.
  • [41]Song C, Zhao S: Omega-3 fatty acid eicosapentaenoic acid (EPA), a new drug in treatment psychiatric and neurodegenerative diseases: a review of clinical trials. Exp Opin Inv Drug 2007, 16:1627-38.
  • [42]Beltz BS, Tlusty MF, Benton JL, Sandeman DC: Omega-3 fatty acids upregulate adult neurogenesis. Neurosci Lett 2007, 145:154-8.
  • [43]Song C, Zhang XY, Manku M: Increased phospholipase A2 activity and inflammatory response but decreased nerve growth factor expression in the olfactory bulbectomized rat model of depression: effects of chronic ethyl-eicosapentaenoate treatment. J Neurosci 2009, 29:14-22.
  • [44]Beck RD Jr, Wasserfull C, Ha GK, Cushman JD, Huang Z, Atkinson MA, Petitto JM: Changes in hippocampal IL-15, related cytokines, and neurogenesis in IL-2 deficient mice. Brain Res 2005, 1041:223-30.
  • [45]Taepavarapruk P, Song C: Reductions of acetylcholine release and nerve growth factor expression are correlated with memory impairment induced by interleukin-1beta administrations: effects of omega-3 fatty acid EPA treatment. J Neurochem 2010, 112:1054-64.
  • [46]Ueda S, Sakakibara S, Yoshimoto K: Effect of long-lasting serotonin depletion on environmental enrichment-induced neurogenesis in adult rat hippocampus and spatial learning. Neuroscience 2005, 135:395-402.
  • [47]Beltz BS, Sandeman DC: Regulation of life-long neurogenesis in the decapod crustacean brain. Arth Struct Dev 2003, 32:39-60.
  • [48]Wu A, Ying Z, Gomez-Pinilla F: Dietary omega-3 fatty acids normalize BDNF levels, reduce oxidative damage, and counteract learning disability after traumatic brain injury in rats. J Neurotrauma 2004, 21:1457-67.
  • [49]Kou W, Luchtman D, Song C: Eicosapentaenoic acid (EPA) increases cell viability and expression of neurotrophin receptors in retinoic acid and brain-derived neurotrophic factor Differentiated SH-SY5Y cells. Eur J Nutr 2008, 47:104-13.
  • [50]Malnoe A, Milon H, Reme C: Effect of in vivo modulation of membrane docosahexaenoic acid levels on the dopamine-dependent adenylate cyclase activity in rat retina. J Neurochem 1990, 55:1480-1485.
  • [51]Witt MR, Nielsen M: Characterization of the influence of unsaturated free fatty acids on brain GABA/benzodiazepine receptor binding in vitro. J Neurochem 1994, 62:1432-1439.
  • [52]Ahmada SO, Park JH, Radel JD, Levant B: Reduced numbers of dopamine neurons in the substantia nigra pars compactaand ventral tegmental area of rats fed an n-3 polyunsaturatedfatty acid-deficient diet: A stereological study. Neuroscience Letters 2008, 438:303-307.
  • [53]Santiago RM, Barbieiro J, Lima MM, Dombrowski PA, Andreatini R, Vital MA: Depressive-like behaviors alterations induced by intranigral MPTP, 6-OHDA, LPS and rotenone models of Parkinson's disease are predominantly associated with serotonin and dopamine. Prog Neuropsychopharmacol Biol Psychiatry 2010, 34:1104-14.
  • [54]Ferraz AC, Delattrea AM, Almendra RG, Sonaglia M, Borges C, Araujo P, Andersen ML, Tufik S, Lima MMS: Chronic ω-3 fatty acids supplementation promotes beneficial effects on anxiety, cognitive and depressive-like behaviors in rats subjected to a restraint stress protocol. Behavioural Brain Research 2011, 219:116-122.
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