The neurobiology of lipid metabolism in autism spectrum disorders

NeuroSignals

Volumn 18, Issue 2, 2011, Pages 98-112

  Tamiji, Javaneh ^a   Crawford, Dorota A ^a  

^a YORK UNIVERSITY   (Canada)

Author keywords

Abnormal fatty acid metabolism; Arachidonic acid; Autism; Dietary supplementation; Genetic defects; Prostaglandins

Indexed keywords

ARACHIDONIC ACID; FATTY ACID; LIPID; PHOSPHOLIPASE A2; PHOSPHOLIPID; PROSTAGLANDIN; PROSTAGLANDIN SYNTHASE;

AUTISM; BIOSYNTHESIS; DIET SUPPLEMENTATION; DISEASE ASSOCIATION; FATTY ACID SYNTHESIS; HUMAN; IMMUNE SYSTEM; LIPID METABOLISM; LIPID PEROXIDATION; METABOLIC REGULATION; MOLECULAR MECHANICS; NEUROBIOLOGY; NONHUMAN; OXIDATIVE STRESS; REVIEW; SIGNAL TRANSDUCTION; SYSTEMATIC REVIEW;

CHILD; CHILD DEVELOPMENT DISORDERS, PERVASIVE; FATTY ACIDS; HUMANS; LIPID METABOLISM; MODELS, BIOLOGICAL; NERVOUS SYSTEM; NEUROBIOLOGY; OXIDATIVE STRESS; SIGNAL TRANSDUCTION;

EID: 79952419593     PISSN: 1424862X     EISSN: None     Source Type: Journal    
DOI: 10.1159/000323189     Document Type: Review

References (267)

1. Folstein SE, Rosen-Sheidley B: Genetics of autism: complex aetiology for a heterogeneous disorder. Nat Rev Genet 2001; 2: 943-955. (Pubitemid 33691091)
2. Fombonne E: Epidemiological surveys of autism and other pervasive developmental disorders: an update. J Autism Dev Disord 2003; 33: 365-382.
3. Inglese MD, Elder JH: Caring for children with autism spectrum disorder. I. Prevalence, etiology, and core features. J Pediatr Nurs 2009; 24: 41-48.
4. Muhle R, Trentacoste SV, Rapin I: The genetics of autism. Pediatrics 2004; 113:e472-e486.
5. Bailey A, Le Couteur A, Gottesman I, Bolton P, Simonoff E, Yuzda E, Rutter M: Autism as a strongly genetic disorder: evidence from a British twin study. Psychol Med 1995; 25: 63-77.
6. Hu VW, Frank BC, Heine S, Lee NH, Quackenbush J: Gene expression profiling of lymphoblastoid cell lines from monozygotic twins discordant in severity of autism reveals differential regulation of neurologically relevant genes. BMC Genomics 2006; 7: 118.
7. Keller F, Persico AM: The neurobiological context of autism. Mol Neurobiol 2003; 28: 1-22. (Pubitemid 38156433)
8. Herbert MR, Russo JP, Yang S, Roohi J, Blaxill M, Kahler SG, Cremer L, Hatchwell E: Autism and environmental genomics. Neurotoxicology 2006; 27: 671-684. (Pubitemid 44232987)
9. Herbert MR: Contributions of the environment and environmentally vulnerable physiology to autism spectrum disorders. Curr Opin Neurol 2010; 23: 103-110.
10. Ming X, Stein TP, Brimacombe M, Johnson WG, Lambert GH, Wagner GC: Increased excretion of a lipid peroxidation biomarker in autism. Prostaglandins Leukot Essent Fatty Acids 2005; 73: 379-384. (Pubitemid 41375634)
11. Chauhan A, Chauhan V, Brown WT, Cohen I: Oxidative stress in autism: increased lipid peroxidation and reduced serum levels of ceruloplasmin and transferrin - the antioxidant proteins. Life Sci 2004; 75: 2539-2549. (Pubitemid 39195260)
12. James SJ, Cutler P, Melnyk S, Jernigan S, Janak L, Gaylor DW, Neubrander JA: Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. Am J Clin Nutr 2004; 80: 1611-1617. (Pubitemid 41103861)
13. Tassoni D, Kaur G, Weisinger RS, Sinclair AJ: The role of eicosanoids in the brain. Asia Pac J Clin Nutr 2008; 17(suppl 1):220-228.
14. Bell JG, MacKinlay EE, Dick JR, MacDonald DJ, Boyle RM, Glen AC: Essential fatty acids and phospholipase A2 in autistic spectrum disorders. Prostaglandins Leukot Essent Fatty Acids 2004; 71: 201-204. (Pubitemid 39037633)
15. Meguid NA, Atta HM, Gouda AS, Khalil RO: Role of polyunsaturated fatty acids in the management of Egyptian children with autism. Clin Biochem 2008; 41: 1044-1048.
16. Haag M: Essential fatty acids and the brain. Can J Psychiatry 2003; 48: 195-203.
17. DeMar JC Jr, Lee HJ, Ma K, Chang L, Bell JM, Rapoport SI, Bazinet RP: Brain elongation of linoleic acid is a negligible source of the arachidonate in brain phospholipids of adult rats. Biochim Biophys Acta 2006; 1761: 1050-1059. (Pubitemid 44354290)
18. Boland LM, Drzewiecki MM, Timoney G, Casey E: Inhibitory effects of polyunsaturated fatty acids on Kv4/KChIP potassium channels. Am j Physiol 2009; 296:C1003-C1014.
19. Guizy M, David M, Arias C, Zhang L, Cofan M, Ruiz-Gutierrez V, Ros E, Lillo MP, Martens JR, Valenzuela C: Modulation of the atrial specific Kv1.5 channel by the n-3 polyunsaturated fatty acid, alpha-linolenic acid. J Mol Cell Cardiol 2008; 44: 323-335.
20. Giusto NM, Pasquare SJ, Salvador GA, Castagnet PI, Roque ME, Ilincheta de Boschero MG: Lipid metabolism in vertebrate retinal rod outer segments. Prog Lipid Res 2000; 39: 315-391. (Pubitemid 30336471)
21. Hoffman DR, Boettcher JA, Diersen-Schade DA: Toward optimizing vision and cognition in term infants by dietary docosahexaenoic and arachidonic acid supplementation: a review of randomized controlled trials. Prostaglandins Leukot Essent Fatty Acids 2009; 81: 151-158.
22. Innis SM: Dietary (n-3) fatty acids and brain development. J Nutr 2007; 137: 855-859.
23. He C, Qu X, Cui L, Wang J, Kang JX: Improved spatial learning performance of fat-1 mice is associated with enhanced neurogenesis and neuritogenesis by docosahexaenoic acid. Proc Natl Acad Sci USA 2009; 106: 11370-11375.
24. Katakura M, Hashimoto M, Shahdat HM, Gamoh S, Okui T, Matsuzaki K, Shido O: Docosahexaenoic acid promotes neuronal differentiation by regulating basic helixloop-helix transcription factors and cell cycle in neural stem cells. Neuroscience 2009; 160: 651-660.
25. Cysneiros RM, Ferrari D, Arida RM, Terra VC, de Almeida AC, Cavalheiro EA, Scorza FA: Qualitative analysis of hippocampal plastic changes in rats with epilepsy supplemented with oral omega-3 fatty acids. Epilepsy Behav 2010; 17: 33-38.
26. Wu A, Ying Z, Gomez-Pinilla F: Docosahexaenoic acid dietary supplementation enhances the effects of exercise on synaptic plasticity and cognition. Neuroscience 2008; 155: 751-759.
27. Orr SK, Bazinet RP: The emerging role of docosahexaenoic acid in neuroinflammation. Curr Opin Investig Drugs 2008; 9: 735-743. (Pubitemid 351950870)
28. Kang JX, Weylandt KH: Modulation of inflammatory cytokines by omega-3 fatty acids. Subcell Biochem 2008; 49: 133-143.
29. Ferrucci L, Cherubini A, Bandinelli S, Bartali B, Corsi A, Lauretani F, Martin A, Andres-Lacueva C, Senin U, Guralnik JM: Relationship of plasma polyunsaturated fatty acids to circulating inflammatory markers. J Clin Endocrinol Metab 2006; 91: 439-446. (Pubitemid 43236907)
30. Shohami E, Cotev S, Shapira Y: The role of eicosanoids in the development of delayed brain damage. J Basic Clin Physiol Pharmacol 1990; 1: 203-206.
31. Yehuda S, Rabinovitz S, Mostofsky DI: Essential fatty acids are mediators of brain biochemistry and cognitive functions. J Neurosci Res 1999; 56: 565-570. (Pubitemid 29246838)
32. Gamoh S, Hashimoto M, Sugioka K, Shahdat Hossain M, Hata N, Misawa Y, Masumura S: Chronic administration of docosahexaenoic acid improves reference memory-related learning ability in young rats. Neuroscience 1999; 93: 237-241. (Pubitemid 29290703)
33. Carrie I, Smirnova M, Clement M, De JD, Frances H, Bourre JM: Docosahexaenoic acid-rich phospholipid supplementation: effect on behavior, learning ability, and retinal function in control and n-3 polyunsaturated fatty acid deficient old mice. Nutr Neurosci 2002; 5: 43-52. (Pubitemid 34228993)
34. Kitajka K, Sinclair AJ, Weisinger RS, Weisinger HS, Mathai M, Jayasooriya AP, Halver JE, Puskas LG: Effects of dietary omega-3 polyunsaturated fatty acids on brain gene expression. Proc Natl Acad Sci USA 2004; 101: 10931-10936. (Pubitemid 38989562)
35. Neuringer M, Reisbick S, Janowsky J: The role of n-3 fatty acids in visual and cognitive development: current evidence and methods of assessment. J Pediatr 1994; 125:S39-S47. (Pubitemid 24347801)
36. Kitajka K, Puskas LG, Zvara A, Hackler L Jr, Barcelo-Coblijn G, Yeo YK, Farkas T: The role of n-3 polyunsaturated fatty acids in brain: modulation of rat brain gene expression by dietary n-3 fatty acids. Proc Natl Acad Sci USA 2002; 99: 2619-2624. (Pubitemid 34240510)
37. Barcelo-Coblijn G, Kitajka K, Puskas LG, Hogyes E, Zvara A, Hackler L Jr, Farkas T: Gene expression and molecular composition of phospholipids in rat brain in relation to dietary n-6 to n-3 fatty acid ratio. Biochim Biophys Acta 2003; 1632: 72-79. (Pubitemid 36628118)
38. Bazan NG: Synaptic lipid signaling: significance of polyunsaturated fatty acids and platelet-activating factor. J Lipid Res 2003; 44: 2221-2233.
39. DeWille JW, Farmer SJ: Postnatal dietary fat influences mRNAs involved in myelination. Dev Neurosci 1992; 14: 61-68.
40. Sun GY, Xu J, Jensen MD, Simonyi A: Phospholipase A2 in the central nervous system: implications for neurodegenerative diseases. J Lipid Res 2004; 45: 205-213. (Pubitemid 38228817)
41. Chen C, Bazan NG: Lipid signaling: sleep, synaptic plasticity, and neuroprotection. Prostaglandins Other Lipid Mediat 2005; 77: 65-76. (Pubitemid 41133416)
42. Breyer RM, Bagdassarian CK, Myers SA, Breyer MD: Prostanoid receptors: subtypes and signaling. Annu Rev Pharmacol Toxicol 2001; 41: 661-690. (Pubitemid 32385902)
43. Narumiya S, Sugimoto Y, Ushikubi F: Prostanoid receptors: structures, properties, and functions. Physiol Rev 1999; 79: 1193-1226. (Pubitemid 29473315)
44. Boie Y, Stocco R, Sawyer N, Slipetz DM, Ungrin MD, Neuschafer-Rube F, Puschel GP, Metters KM, Abramovitz M: Molecular cloning and characterization of the four rat prostaglandin E2 prostanoid receptor subtypes. Eur J Pharmacol 1997; 340: 227-241. (Pubitemid 28022647)
45. Sang N, Chen C: Lipid signaling and synaptic plasticity. Neuroscientist 2006; 12: 425-434.
46. Kitaoka S, Furuyashiki T, Nishi A, Shuto T, Koyasu S, Matsuoka T, Miyasaka M, Greengard P, Narumiya S: Prostaglandin E2 acts on EP1 receptor and amplifies both dopamine D1 and D2 receptor signaling in the striatum. J Neurosci 2007; 27: 12900-12907.
47. Chen C, Bazan NG: Endogenous PGE2 regulates membrane excitability and synaptic transmission in hippocampal CA1 pyramidal neurons. J Neurophysiol 2005; 93: 929-941.
48. Sang N, Zhang J, Marcheselli V, Bazan NG, Chen C: Postsynaptically synthesized prostaglandin E2 (PGE2) modulates hippocampal synaptic transmission via a presynaptic PGE2 EP2 receptor. J Neurosci 2005; 25: 9858-9870. (Pubitemid 41528023)
49. Crawford MA: Essential fatty acids and neurodevelopmental disorder. Adv Exp Med Biol 1992; 318: 307-314.
50. O'Connor DL, Jacobs J, Hall R, Adamkin D, Auestad N, Castillo M, Connor WE, Connor SL, Fitzgerald K, Groh-Wargo S, Hartmann EE, Janowsky J, Lucas A, Margeson D, Mena P, Neuringer M, Ross G, Singer L, Stephenson T, Szabo J, Zemon V: Growth and development of premature infants fed predominantly human milk, predominantly premature infant formula, or a combination of human milk and premature formula. J Pediatr Gastroenterol Nutr 2003; 37: 437-446. (Pubitemid 39274488)
51. Young G, Conquer J: Omega-3 fatty acids and neuropsychiatric disorders. Reprod Nutr Dev 2005; 45: 1-28. (Pubitemid 40528530)
52. Axelrod J: Receptor-mediated activation of phospholipase A2 and arachidonic acid release in signal transduction. Biochem Soc Trans 1990; 18: 503-507.
53. Martinez M: Tissue levels of polyunsaturated fatty acids during early human development. J Pediatr 1992; 120:S129-138.
54. Lauritzen L, Hansen HS, Jorgensen MH, Michaelsen KF: The essentiality of long chain n-3 fatty acids in relation to development and function of the brain and retina. Prog Lipid Res 2001; 40: 1-94. (Pubitemid 32008650)
55. Murphy MG: Dietary fatty acids and membrane protein function. J Nutr Biochem 1990; 1: 68-79.
56. Muskiet FA, Kemperman RF: Folate and long-chain polyunsaturated fatty acids in psychiatric disease. J Nutr Biochem 2006; 17: 717-727. (Pubitemid 44557052)
57. Crawford MA, Golfetto I, Ghebremeskel K, Min Y, Moodley T, Poston L, Phylactos A, Cunnane S, Schmidt W: The potential role for arachidonic and docosahexaenoic acids in protection against some central nervous system injuries in preterm infants. Lipids 2003; 38: 303-315. (Pubitemid 36724287)
58. Chen CT, Green JT, Orr SK, Bazinet RP: Regulation of brain polyunsaturated fatty acid uptake and turnover. Prostaglandins Leukot Essent Fatty Acids 2008; 79: 85-91.
59. Helland IB, Smith L, Saarem K, Saugstad OD, Drevon CA: Maternal supplementation with very-long-chain n-3 fatty acids during pregnancy and lactation augments children's IQ at 4 years of age. Pediatrics 2003; 111:e39-e44.
60. Birch EE, Garfield S, Hoffman DR, Uauy R, Birch DG: A randomized controlled trial of early dietary supply of long-chain polyunsaturated fatty acids and mental development in term infants. Dev Med Child Neurol 2000; 42: 174-181. (Pubitemid 30145332)
61. Fedorova I, Hussein N, Di Martino C, Moriguchi T, Hoshiba J, Majchrzak S, Salem N Jr: An n-3 fatty acid deficient diet affects mouse spatial learning in the Barnes circular maze. Prostaglandins Leukot Essent Fatty Acids 2007; 77: 269-277. (Pubitemid 350198859)
62. Jacobson JL, Jacobson SW, Muckle G, Kaplan-Estrin M, Ayotte P, Dewailly E: Beneficial effects of a polyunsaturated fatty acid on infant development: evidence from the Inuit of Arctic Quebec. J Pediatr 2008; 152: 356-364.
63. Coluccia A, Borracci P, Renna G, Giustino A, Latronico T, Riccio P, Carratu MR: Developmental omega-3 supplementation improves motor skills in juvenile-adult rats. Int J Dev Neurosci 2009; 27: 599-605.
64. Richardson AJ, Ross MA: Fatty acid metabolism in neurodevelopmental disorder: a new perspective on associations between attention-deficit/ hyperactivity disorder, dyslexia, dyspraxia and the autistic spectrum. Prostaglandins Leukot Essent Fatty Acids 2000; 63: 1-9.
65. Kidd PM: Omega-3 DHA and EPA for cognition, behavior, and mood: clinical findings and structural-functional synergies with cell membrane phospholipids. Altern Med Rev 2007; 12: 207-227.
66. Stevens LJ, Zentall SS, Deck JL, Abate ML, Watkins BA, Lipp SR, Burgess JR: Essential fatty acid metabolism in boys with attention-deficit hyperactivity disorder. Am J Clin Nutr 1995; 62: 761-768.
67. Colter AL, Cutler C, Meckling KA: Fatty acid status and behavioural symptoms of attention deficit hyperactivity disorder in adolescents: a case-control study. Nutr J 2008; 7: 8.
68. Schuchardt JP, Huss M, Stauss-Grabo M, Hahn A: Significance of long-chain polyunsaturated fatty acids (PUFAs) for the development and behaviour of children. Eur J Pediatr 2010; 169: 149-164.
69. Burgess JR, Stevens L, Zhang W, Peck L: Long-chain polyunsaturated fatty acids in children with attention-deficit hyperactivity disorder. Am J Clin Nutr 2000; 71: 327S-330S.
70. Khan MM, Evans DR, Gunna V, Scheffer RE, Parikh VV, Mahadik SP: Reduced erythrocyte membrane essential fatty acids and increased lipid peroxides in schizophrenia at the never-medicated first-episode of psychosis and after years of treatment with antipsychotics. Schizophr Res 2002; 58: 1-10. (Pubitemid 35287278)
71. Muller N, Riedel M, Scheppach C, Brandstatter B, Sokullu S, Krampe K, Ulmschneider M, Engel RR, Moller HJ, Schwarz MJ: Beneficial antipsychotic effects of celecoxib add-on therapy compared to risperidone alone in schizophrenia. Am J Psychiatry 2002; 159: 1029-1034. (Pubitemid 34586950)
72. Schultz ST, Klonoff-Cohen HS, Wingard DL, Akshoomoff NA, Macera CA, Ji M, Bacher C: Breastfeeding, infant formula supplementation, and autistic disorder: The results of a parent survey. Int Breastfeed J 2006; 1: 16.
73. Vancassel S, Durand G, Barthelemy C, Lejeune B, Martineau J, Guilloteau D, Andres C, Chalon S: Plasma fatty acid levels in autistic children. Prostaglandins Leukot Essent Fatty Acids 2001; 65: 1-7. (Pubitemid 32783435)
74. Mostafa GA, El-Hadidi ES, Hewedi DH, Abdou MM: Oxidative stress in Egyptian children with autism: relation to autoimmunity. J Neuroimmunol 2010; 219: 114-118.
75. 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: 221-227.
76. Bell JG, Miller D, MacDonald DJ, MacKinlay EE, Dick JR, Cheseldine S, Boyle RM, Graham C, O'Hare AE: The fatty acid compositions of erythrocyte and plasma polar lipids in children with autism, developmental delay or typically developing controls and the effect of fish oil intake. Br J Nutr 2010; 103: 1160-1167.
77. Sliwinski S, Croonenberghs J, Christophe A, Deboutte D, Maes M: Polyunsaturated fatty acids: do they have a role in the pathophysiology of autism? Neuro Endocrinol Lett 2006; 27: 465-471.
78. Pastural E, Ritchie S, Lu Y, Jin W, Kavianpour A, Khine Su-Myat K, Heath D, Wood PL, Fisk M, Goodenowe DB: Novel plasma phospholipid biomarkers of autism: mitochondrial dysfunction as a putative causative mechanism. Prostaglandins Leukot Essent Fatty Acids 2009; 81: 253-264.
79. MacFabe DF, Cain DP, Rodriguez-Capote K, Franklin AE, Hoffman JE, Boon 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. Behav Brain Res 2007; 176: 149-169. (Pubitemid 44895353)
80. Shultz SR, Macfabe DF, Martin S, Jackson J, Taylor R, Boon F, Ossenkopp KP, Cain DP: Intracerebroventricular injections of the enteric bacterial metabolic product propionic acid impair cognition and sensorimotor ability in the Long-Evans rat: further development of a rodent model of autism. Behav Brain Res 2009; 200: 33-41.
81. Shultz SR, MacFabe DF, Ossenkopp KP, Scratch S, Whelan J, Taylor R, Cain DP: Intracerebroventricular injection of propionic acid, an enteric bacterial metabolic endproduct, impairs social behavior in the rat: implications for an animal model of autism. Neuropharmacology 2008; 54: 901-911.
82. Thomas RH, Foley KA, Mepham JR, Tichenoff LJ, Possmayer F, MacFabe DF: Altered brain phospholipid and acylcarnitine profiles in propionic acid infused rodents: further development of a potential model of autism spectrum disorders. J Neurochem 2010; 113: 515-529.
83. Amminger GP, Berger GE, Schafer MR, Klier C, Friedrich MH, Feucht M: Omega-3 fatty acids supplementation in children with autism: a double-blind randomized, placebocontrolled pilot study. Biol Psychiatry 2007; 61: 551-553. (Pubitemid 46185334)
84. Filipek PA, Juranek J, Nguyen MT, Cummings C, Gargus JJ: Relative carnitine deficiency in autism. J Autism Dev Disord 2004; 34: 615-623. (Pubitemid 40044667)
85. Ma DQ, Cuccaro ML, Jaworski JM, Haynes CS, Stephan DA, Parod J, Abramson RK, Wright HH, Gilbert JR, Haines JL, Pericak-Vance MA: Dissecting the locus heterogeneity of autism: significant linkage to chromosome 12q14. Mol Psychiatry 2007; 12: 376-384. (Pubitemid 46496833)
86. Brookes KJ, Chen W, Xu X, Taylor E, Asherson P: Association of fatty acid desaturase genes with attention-deficit/hyperactivity disorder. Biol Psychiatry 2006; 60: 1053-1061. (Pubitemid 44647221)
87. Schaeffer L, Gohlke H, Muller M, Heid IM, Palmer LJ, Kompauer I, Demmelmair H, Illig T, Koletzko B, Heinrich J: Common genetic variants of the FADS1 FADS2 gene cluster and their reconstructed haplotypes are associated with the fatty acid composition in phospholipids. Hum Mol Genet 2006; 15: 1745-1756. (Pubitemid 43821765)
88. Fallin MD, Lasseter VK, Wolyniec PS, Mc-Grath JA, Nestadt G, Valle D, Liang KY, Pulver AE: Genomewide linkage scan for bipolar-disorder susceptibility loci among Ashkenazi Jewish families. Am J Hum Genet 2004; 75: 204-219. (Pubitemid 38943864)
89. Murakami M, Kudo I: Phospholipase A2. J Biochem 2002; 131: 285-292.
90. 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.
91. Massicotte G: Modification of glutamate receptors by phospholipase A2: its role in adaptive neural plasticity. Cell Mol Life Sci 2000; 57: 1542-1550.
92. Marin P, Hamon B, Glowinski J, Premont J: Nicotine-induced inhibition of neuronal phospholipase A2. J Pharmacol Exp Ther 1997; 280: 1277-1283. (Pubitemid 27166724)
93. Navamani M, Morgan M, Williams RJ: Ethanol modulates n-methyl- D -aspartate-evoked arachidonic acid release from neurones. Eur J Pharmacol 1997; 340: 27-34. (Pubitemid 28033972)
94. Williams RJ, Glowinski J: Cyclothiazide unmasks an AMPA-evoked release of arachidonic acid from cultured striatal neurones. J Neurochem 1996; 67: 1551-1558. (Pubitemid 26314212)
95. Farooqui AA, Horrocks LA, Farooqui T: Modulation of inflammation in brain: a matter of fat. J Neurochem 2007; 101: 577-599. (Pubitemid 46633316)
96. Horrobin DF, Bennett CN: New gene targets related to schizophrenia and other psychiatric disorders: enzymes, binding proteins and transport proteins involved in phospholipid and fatty acid metabolism. Prostaglandins Leukot Essent Fatty Acids 1999; 60: 141-167. (Pubitemid 29213885)
97. Fenton WS, Hibbeln J, Knable M: Essential fatty acids, lipid membrane abnormalities, and the diagnosis and treatment of schizophrenia. Biol Psychiatry 2000; 47: 8-21. (Pubitemid 30016075)
98. Smesny S, Kinder D, Willhardt I, Rosburg T, Lasch J, Berger G, Sauer H: Increased calcium-independent phospholipase A2 activity in first but not in multiepisode chronic schizophrenia. Biol Psychiatry 2005; 57: 399-405. (Pubitemid 40215770)
99. Gattaz WF, Kollisch M, Thuren T, Virtanen JA, Kinnunen PK: Increased plasma phospholipase-A2 activity in schizophrenic patients: reduction after neuroleptic therapy. Biol Psychiatry 1987; 22: 421-426. (Pubitemid 17041622)
100. Wei J, Lee KH, Hemmings GP: Is the cPLA2 gene associated with schizophrenia? Mol Psychiatry 1998; 3: 480-481.
101. Peet M, Ramchand CN, Lee J, Telang SD, Vankar GK, Shah S, Wei J: Association of the Ban I dimorphic site at the human cytosolic phospholipase A2 gene with schizophrenia. Psychiatr Genet 1998; 8: 191-192. (Pubitemid 28479016)
102. Pae CU, Yu HS, Lee KU, Kim JJ, Lee CU, Lee SJ, Jun TY, Lee C, Paik IH: BanI polymorphism of the cytosolic phospholipase A2 gene may confer susceptibility to the development of schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2004; 28: 739-741. (Pubitemid 38987400)
103. Tao R, Yu Y, Zhang X, Guo Y, Shi J, Zhang X, Xie L, Liu S, Ju G, Xu Q, Shen Y, Wei J: Cytosolic PLA2 genes possibly contribute to the etiology of schizophrenia. Am J Med Genet B Neuropsychiatr Genet 2005; 137B:56-58. (Pubitemid 41076615)
104. Meyer AH, Schmuck K, Morel C, Wishart W, Lubbert H, Engels P: Localization of a gene coding for the phospholipase A2-L subtype (PLA2L) to human chromosome 8q24-qter. Genomics 1996; 38: 435-437. (Pubitemid 27030135)
105. Kudo I, Murakami M: Phospholipase A2 enzymes. Prostaglandins Other Lipid Mediat 2002; 68-69: 3-58.
106. Combi R, Redaelli S, Beghi M, Clerici M, Cornaggia CM, Dalpra L: Clinical and genetic evaluation of a family showing both autism and epilepsy. Brain Res Bull 2010; 82: 25-28.
107. Chen GK, Kono N, Geschwind DH, Cantor RM: Quantitative trait locus analysis of nonverbal communication in autism spectrum disorder. Mol Psychiatry 2006; 11: 214-220. (Pubitemid 43164623)
108. Lai CS, Fisher SE, Hurst JA, Levy ER, Hodgson S, Fox M, Jeremiah S, Povey S, Jamison DC, Green ED, Vargha-Khadem F, Monaco AP: The SPCH1 region on human 7q31: genomic characterization of the critical interval and localization of translocations associated with speech and language disorder. Am J Hum Genet 2000; 67: 357-368. (Pubitemid 30616741)
109. Bell JG, Miller D, MacDonald DJ, MacKinlay EE, Dick JR, Cheseldine S, Boyle RM, Graham C, O'Hare AE: The fatty acid compositions of erythrocyte and plasma polar lipids in children with autism, developmental delay or typically developing controls and the effect of fish oil intake. Br J Nutr 2010; 103: 1160-1167.
110. Marty V, El Hachmane M, Amedee T: Dual modulation of synaptic transmission in the nucleus tractus solitarius by prostaglandin E2 synthesized downstream of IL-1beta. Eur J Neurosci 2008; 27: 3132-3150. (Pubitemid 351847319)
111. Yang H, Chen C: Cyclooxygenase-2 in synaptic signaling. Curr Pharm Des 2008; 14: 1443-1451. (Pubitemid 351993045)
112. Chen C, Magee JC, Bazan NG: Cyclooxygenase-2 regulates prostaglandin E2 signaling in hippocampal long-term synaptic plasticity. J Neurophysiol 2002; 87: 2851-2857. (Pubitemid 34670665)
113. Smith HS: Arachidonic acid pathways in nociception. J Suppor Oncol 2006; 4: 277-287.
114. Pepicelli O, Fedele E, Berardi M, Raiteri M, Levi G, Greco A, Ajmone-Cat MA, Minghetti L: Cyclo-oxygenase-1 and -2 differently contribute to prostaglandin E2 synthesis and lipid peroxidation after in vivo activation of n-methyl- D -aspartate receptors in rat hippocampus. J Neurochem 2005; 93: 1561-1567. (Pubitemid 40853279)
115. Benvenuto A, Manzi B, Alessandrelli R, Galasso C, Curatolo P: Recent advances in the pathogenesis of syndromic autisms. Int J Pediatr 2009; 2009: 198736.
116. Bezzi P, Carmignoto G, Pasti L, Vesce S, Rossi D, Rizzini BL, Pozzan T, Volterra A: Prostaglandins stimulate calcium-dependent glutamate release in astrocytes. Nature 1998; 391: 281-285. (Pubitemid 28099014)
117. Bezzi P, Volterra A: A neuron-glia signalling network in the active brain. Curr Opin Neurobiol 2001; 11: 387-394. (Pubitemid 32524106)
118. Zonta M, Sebelin A, Gobbo S, Fellin T, Pozzan T, Carmignoto G: Glutamate-mediated cytosolic calcium oscillations regulate a pulsatile prostaglandin release from cultured rat astrocytes. J Physiol 2003; 553: 407-414. (Pubitemid 37527544)
119. Minghetti L: Cyclooxygenase-2 (COX-2) in inflammatory and degenerative brain diseases. J Neuropathol Exp Neurol 2004; 63: 901-910.
120. Kim HW, Rapoport SI, Rao JS: Altered arachidonic acid cascade enzymes in postmortem brain from bipolar disorder patients. Mol Psychiatry 2009, Epub ahead of print.
121. Ho L, Pieroni C, Winger D, Purohit DP, Aisen PS, Pasinetti GM: Regional distribution of cyclooxygenase-2 in the hippocampal formation in Alzheimer's disease. J Neurosci Res 1999; 57: 295-303. (Pubitemid 29339785)
122. Lipsky PE, Brooks P, Crofford LJ, DuBois R, Graham D, Simon LS, van de Putte LB, Abramson SB: Unresolved issues in the role of cyclooxygenase-2 in normal physiologic processes and disease. Arch Intern Med 2000; 160: 913-920. (Pubitemid 30191918)
123. Ashwood P, Wills S, Van de Water J: The immune response in autism: a new frontier for autism research. J Leukoc Biol 2006; 80: 1-15. (Pubitemid 44841805)
124. Ashwood P, Van de Water J: A review of autism and the immune response. Clin Dev Immunol 2004; 11: 165-174. (Pubitemid 38955074)
125. Yoo HJ, Cho IH, Park M, Cho E, Cho SC, Kim BN, Kim JW, Kim SA: Association between PTGS2 polymorphism and autism spectrum disorders in Korean trios. Neurosci Res 2008; 62: 66-69.
126. Kaufmann WE, Worley PF, Taylor CV, Bremer M, Isakson PC: Cyclooxygenase-2 expression during rat neocortical development and in Rett syndrome. Brain Dev 1997; 19: 25-34. (Pubitemid 27116980)
127. Narumiya S: Prostanoid receptors. Structure, function, and distribution. Ann N Y Acad Sci 1994; 744: 126-138.
128. Abramovitz M, Adam M, Boie Y, Carriere M, Denis D, Godbout C, Lamontagne S, Rochette C, Sawyer N, Tremblay NM, Belley M, Gallant M, Dufresne C, Gareau Y, Ruel R, Juteau H, Labelle M, Ouimet N, Metters KM: The utilization of recombinant prostanoid receptors to determine the affinities and selectivities of prostaglandins and related analogs. Biochim Biophys Acta 2000; 1483: 285-293. (Pubitemid 30029060)
129. Coleman RA, Smith WL, Narumiya S: International union of pharmacology classification of prostanoid receptors: properties, distribution, and structure of the receptors and their subtypes. Pharmacol Rev 1994; 46: 205-229. (Pubitemid 24185151)
130. Minami T, Nakano H, Kobayashi T, Sugimoto Y, Ushikubi F, Ichikawa A, Narumiya S, Ito S: Characterization of EP receptor subtypes responsible for prostaglandin E2-induced pain responses by use of EP1 and EP3 receptor knockout mice. Br J Pharmacol 2001; 133: 438-444. (Pubitemid 33027781)
131. Boniface K, Bak-Jensen KS, Li Y, Blumenschein WM, McGeachy MJ, McClanahan TK, McKenzie BS, Kastelein RA, Cua DJ, de Waal Malefyt R: Prostaglandin E2 regulates TH17 cell differentiation and function through cyclic AMP and EP2/EP4 receptor signaling. J Exp Med 2009; 206: 535-548.
132. Buvanendran A, Kroin JS, Berger RA, Hallab NJ, Saha C, Negrescu C, Moric M, Caicedo MS, Tuman KJ: Upregulation of prostaglandin E2 and interleukins in the central nervous system and peripheral tissue during and after surgery in humans. Anesthesiology 2006; 104: 403-410.
133. Di Cesare A, Del Piccolo P, Zacchetti D, Grohovaz F: EP2 receptor stimulation promotes calcium responses in astrocytes via activation of the adenylyl cyclase pathway. Cell Mol Life Sci 2006; 63: 2546-2553. (Pubitemid 44722384)
134. Furuyashiki T, Narumiya S: Roles of prostaglandin E receptors in stress responses. Curr Opin Pharmacol 2009; 9: 31-38.
135. Lazarus M: The differential role of prostaglandin E2 receptors EP3 and EP4 in regulation of fever. Mol Nutr Food Res 2006; 50: 451-455.
136. Burks SR, Wright CL, McCarthy MM: Exploration of prostanoid receptor subtype regulating estradiol and prostaglandin E2 induction of spinophilin in developing preoptic area neurons. Neuroscience 2007; 146: 1117-1127. (Pubitemid 46694121)
137. Pastuszak AL, Schuler L, Speck-Martins CE, Coelho KE, Cordello SM, Vargas F, Brunoni D, Schwarz IV, Larrandaburu M, Safattle H, Meloni VF, Koren G: Use of misoprostol during pregnancy and Mobius' syndrome in infants. N Engl J Med 1998; 338: 1881-1885. (Pubitemid 28287860)
138. Miller MT, Stromland K, Ventura L, Johansson M, Bandim JM, Gillberg C: Autism associated with conditions characterized by developmental errors in early embryogenesis: a mini review. Int J Dev Neurosci 2005; 23: 201-219. (Pubitemid 40313553)
139. Bandim JM, Ventura LO, Miller MT, Almeida HC, Costa AE: Autism and Mobius sequence: an exploratory study of children in northeastern Brazil. Arq Neuropsiquiatr 2003; 61: 181-185. (Pubitemid 36648708)
140. Schuler L, Pastuszak A, Sanseverino TV, Orioli IM, Brunoni D, Ashton-Prolla P, Silva da Costa F, Giugliani R, Couto AM, Brandao SB, Koren G: Pregnancy outcome after exposure to misoprostol in Brazil: a prospective, controlled study. Reprod Toxicol (Elmsford) 1999; 13: 147-151. (Pubitemid 29165846)
141. Gonzalez CH, Marques-Dias MJ, Kim CA, Sugayama SM, Da Paz JA, Huson SM, Holmes LB: Congenital abnormalities in Brazilian children associated with misoprostol misuse in first trimester of pregnancy. Lancet 1998; 351: 1624-1627. (Pubitemid 28252179)
142. Gonzalez CH, Vargas FR, Perez AB, Kim CA, Brunoni D, Marques-Dias MJ, Leone CR, Correa Neto J, Llerena Junior JC, de Almeida JC: Limb deficiency with or without Mobius sequence in seven Brazilian children associated with misoprostol use in the first trimester of pregnancy. Am J Med Genet 1993; 47: 59-64. (Pubitemid 23221528)
143. Marques-Dias MJ, Gonzalez CH, Rosemberg S: Mobius sequence in children exposed in utero to misoprostol: neuropathological study of three cases. Birth Defects Res A Clin Mol Teratol 2003; 67: 1002-1007. (Pubitemid 38018044)
144. Costa SH: Commercial availability of misoprostol and induced abortion in Brazil. Int J Gynaecol Obstet 1998; 63(suppl 1):S131-S139.
145. Vonkeman HE, van de Laar MA: Nonsteroidal anti-inflammatory drugs: adverse effects and their prevention. Semin Arthritis Rheum 2010; 39: 294-312.
146. Davies NM, Longstreth J, Jamali F: Misoprostol therapeutics revisited. Pharmacotherapy 2001; 21: 60-73. (Pubitemid 32047576)
147. Gemzell-Danielsson K, Lalitkumar S: Second trimester medical abortion with mifepristone-misoprostol and misoprostol alone: a review of methods and management. Reprod Health Matters 2008; 16: 162-172.
148. Genest DR, Di Salvo D, Rosenblatt MJ, Holmes LB: Terminal transverse limb defects with tethering and omphalocele in a 17 week fetus following first trimester misoprostol exposure. Clin Dysmorphol 1999; 8: 53-58. (Pubitemid 29095260)
149. Tamiji J, Crawford DA: Misoprostol elevates intracellular calcium in neuro-2A cells via protein kinase A. Biochem Biophys Res Commun 2010; 399: 565-570.
150. Tamiji J, Crawford DA: Prostaglandin E 2 and misoprostol induce neurite retraction in neuro-2a cells. Biochem Biophys Res Commun 2010; 398: 450-456.
151. Splawski I, Timothy KW, Sharpe LM, Decher N, Kumar P, Bloise R, Napolitano C, Schwartz PJ, Joseph RM, Condouris K, Tager-Flusberg H, Priori SG, Sanguinetti MC, Keating MT: Ca(v)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism. Cell 2004; 119: 19-31.
152. Splawski I, Timothy KW, Decher N, Kumar P, Sachse FB, Beggs AH, Sanguinetti MC, Keating MT: Severe arrhythmia disorder caused by cardiac l-type calcium channel mutations. Proc Natl Acad Sci U S A 2005; 102: 8089-8096; discussion 8086-8088.
153. Splawski I, Yoo DS, Stotz SC, Cherry A, Clapham DE, Keating MT: CACNA1H mutations in autism spectrum disorders. J Biol Chem 2006; 281: 22085-22091. (Pubitemid 44181912)
154. Barnby G, Abbott A, Sykes N, Morris A, Weeks DE, Mott R, Lamb J, Bailey AJ, Monaco AP: Candidate-gene screening and association analysis at the autism-susceptibility locus on chromosome 16p: evidence of association at GRIN2A and ABAT. Am J Hum Genet 2005; 76: 950-966. (Pubitemid 40705432)
155. Jamain S, Betancur C, Quach H, Philippe A, Fellous M, Giros B, Gillberg C, Leboyer M, Bourgeron T: Linkage and association of the glutamate receptor 6 gene with autism. Mol Psychiatry 2002; 7: 302-310. (Pubitemid 34280638)
156. Serajee FJ, Nabi R, Zhong H, Mahbubul Huq AH: Association of INPP1, PIK3CG, and TSC2 gene variants with autistic disorder: implications for phosphatidylinositol signalling in autism. J Med Genet 2003; 40:e119.
157. 2+ signaling. Curr Opin Neurobiol 2007; 17: 112-119.
158. Oshima H, Oguma K, Du YC, Oshima M: Prostaglandin E2, Wnt, and BMP in gastric tumor mouse models. Cancer Sci 2009; 100: 1779-1785.
159. Ishimoto T, Oshima H, Oshima M, Kai K, Torii R, Masuko T, Baba H, Saya H, Nagano O: CD44+ slow-cycling tumor cell expansion is triggered by cooperative actions of Wnt and prostaglandin E2 in gastric tumorigenesis. Cancer Sci 2010; 101: 673-678.
160. Goessling W, North TE, Loewer S, Lord AM, Lee S, Stoick-Cooper CL, Weidinger G, Puder M, Daley GQ, Moon RT, Zon LI: Genetic interaction of PGE2 and Wnt signaling regulates developmental specification of stem cells and regeneration. Cell 2009; 136: 1136-1147.
161. Evans T: Fishing for a Wnt-PGE2 link: beta-catenin is caught in the stem cell network. Cell Stem Cell 2009; 4: 280-282.
162. Gao Q, Xu M, Alander CB, Choudhary S, Pilbeam CC, Raisz LG: Effects of prostaglandin E2 on bone in mice in vivo. Prostaglandins Other Lipid Mediat 2009; 89: 20-25.
163. Howe LR, Subbaramaiah K, Chung WJ, Dannenberg AJ, Brown AM: Transcriptional activation of cyclooxygenase-2 in Wnt-1-transformed mouse mammary epithelial cells. Cancer Res 1999; 59: 1572-1577. (Pubitemid 29160128)
164. Sanchez-Camacho C, Bovolenta P: Emerging mechanisms in morphogen-mediated axon guidance. Bioessays 2009; 31: 1013-1025.
165. Ille F, Sommer L: Wnt signaling: multiple functions in neural development. Cell Mol Life Sci 2005; 62: 1100-1108. (Pubitemid 40868528)
166. Ciani L, Salinas PC: Wnts in the vertebrate nervous system: from patterning to neuronal connectivity. Nat Rev Neurosci 2005; 6: 351-362. (Pubitemid 40593481)
167. Ulloa F, Marti E: Wnt won the war: antagonistic role of Wnt over Shh controls dorsoventral patterning of the vertebrate neural tube. Dev Dyn 2010; 239: 69-76.
168. Kim D, Jin EJ: Wnt-3 and Wnt-3a plays different region specific role on neural crest development in avian. Cell Biol Int 2010; 34: 763-768.
169. Cadigan KM, Nusse R: Wnt signaling: a common theme in animal development. Genes Dev 1997; 11: 3286-3305. (Pubitemid 28023954)
170. Vincent JB, Herbrick JA, Gurling HM, Bolton PF, Roberts W, Scherer SW: Identification of a novel gene on chromosome 7q31 that is interrupted by a translocation breakpoint in an autistic individual. Am J Hum Genet 2000; 67: 510-514. (Pubitemid 30616754)
171. Ashley-Koch A, Wolpert CM, Menold MM, Zaeem L, Basu S, Donnelly SL, Ravan SA, Powell CM, Qumsiyeh MB, Aylsworth AS, Vance JM, Gilbert JR, Wright HH, Abramson RK, DeLong GR, Cuccaro ML, Pericak-Vance MA: Genetic studies of autistic disorder and chromosome 7. Genomics 1999; 61: 227-236.
172. Wassink TH, Piven J, Vieland VJ, Huang J, Swiderski RE, Pietila J, Braun T, Beck G, Folstein SE, Haines JL, Sheffield VC: Evidence supporting Wnt2 as an autism susceptibility gene. Am J Med Genet 2001; 105: 406-413. (Pubitemid 32601590)
173. Sanchez-Camacho C, Rodriguez J, Ruiz JM, Trousse F, Bovolenta P: Morphogens as growth cone signalling molecules. Brain Res Brain Res Rev 2005; 49: 242-252. (Pubitemid 41160393)
174. Tamiji J, Crawford DA: Prostaglandin E 2 and misoprostol induce neurite retraction in Neuro-2a cells. Biochem Biophys Res Commun 2010; 398: 450-456.
175. Tamiji J, Crawford DA: Misoprostol elevates intracellular calcium in Neuro-2a cells via protein kinase A. Biochem Biophys Res Commun 2010; 399: 565-570.
176. Wayman GA, Impey S, Marks D, Saneyoshi T, Grant WF, Derkach V, Soderling TR: Activity-dependent dendritic arborization mediated by CAM-kinase I activation and enhanced CREB-dependent transcription of Wnt-2. Neuron 2006; 50: 897-909. (Pubitemid 43850689)
177. Ishimoto T, Oshima H, Oshima M, Kai K, Torii R, Masuko T, Baba H, Saya H, Nagano O: CD44+ slow-cycling tumor cell expansion is triggered by cooperative actions of Wnt and prostaglandin E 2 in gastric tumorigenesis. Cancer Sci 2010; 101: 673-678.
178. Rice D, Barone S Jr: Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models. Environment Health Perspect 2000; 108(suppl 3):511-533. (Pubitemid 30466179)
179. Courchesne E: Brain development in autism: early overgrowth followed by premature arrest of growth. Ment Retard Dev Disabil Res Rev 2004; 10: 106-111.
180. Courchesne E, Pierce K, Schumann CM, Redcay E, Buckwalter JA, Kennedy DP, Morgan J: Mapping early brain development in autism. Neuron 2007; 56: 399-413.
181. Amaral DG, Schumann CM, Nordahl CW: Neuroanatomy of autism. Trends Neurosci 2008; 31: 137-145.
182. Sies H: Oxidative stress: oxidants and antioxidants. Exp Physiol 1997; 82: 291-295.
183. Filomeni G, Ciriolo MR: Redox control of apoptosis: an update. Antioxid Redox Signal 2006; 8: 2187-2192. (Pubitemid 46489643)
184. Yehuda S, Rabinovitz S, Carasso RL, Mostofsky DI: The role of polyunsaturated fatty acids in restoring the aging neuronal membrane. Neurobiol Aging 2002; 23: 843-853. (Pubitemid 35217710)
185. Tsaluchidu S, Cocchi M, Tonello L, Puri BK: Fatty acids and oxidative stress in psychiatric disorders. BMC psychiatry 2008; 8(suppl 1):S5.
186. Adibhatla RM, Hatcher JF: Altered lipid metabolism in brain injury and disorders. Subcell Biochem 2008; 49: 241-268.
187. Shulman RG, Rothman DL, Behar KL, Hyder F: Energetic basis of brain activity: implications for neuroimaging. Trends Neurosci 2004; 27: 489-495. (Pubitemid 38951042)
188. Perry SW, Norman JP, Litzburg A, Gelbard HA: Antioxidants are required during the early critical period, but not later, for neuronal survival. J Neurosci Res 2004; 78: 485-492. (Pubitemid 39536492)
189. Chen P, Peng C, Luff J, Spring K, Watters D, Bottle S, Furuya S, Lavin MF: Oxidative stress is responsible for deficient survival and dendritogenesis in Purkinje neurons from ataxia-telangiectasia mutated mutant mice. J Neurosci 2003; 23: 11453-11460. (Pubitemid 37549702)
190. Yamashita T, Ando Y, Obayashi K, Terazaki H, Sakashita N, Uchida K, Ohama E, Ando M, Uchino M: Oxidative injury is present in Purkinje cells in patients with olivopontocerebellar atrophy. J Neurol Sci 2000; 175: 107-110. (Pubitemid 30265476)
191. Bailey A, Luthert P, Dean A, Harding B, Janota I, Montgomery M, Rutter M, Lantos P: A clinicopathological study of autism. Brain 1998; 121: 889-905. (Pubitemid 28220896)
192. Ahlsen G, Rosengren L, Belfrage M, Palm A, Haglid K, Hamberger A, Gillberg C: Glial fibrillary acidic protein in the cerebrospinal fluid of children with autism and other neuropsychiatric disorders. Biol Psychiatry 1993; 33: 734-743. (Pubitemid 23205331)
193. Yorbik O, Sayal A, Akay C, Akbiyik DI, Sohmen T: Investigation of antioxidant enzymes in children with autistic disorder. Prostaglandins Leukot Essent Fatty Acids 2002; 67: 341-343. (Pubitemid 35397373)
194. Zoroglu SS, Armutcu F, Ozen S, Gurel A, Sivasli E, Yetkin O, Meram I: Increased oxidative stress and altered activities of erythrocyte free radical scavenging enzymes in autism. Eur Arch Psychiatry Clin Neurosci 2004; 254: 143-147. (Pubitemid 39304462)
195. Aoyama K, Watabe M, Nakaki T: Regulation of neuronal glutathione synthesis. J Pharmacol Sci 2008; 108: 227-238.
196. Ono H, Sakamoto A, Sakura N: Plasma total glutathione concentrations in healthy pediatric and adult subjects. Clin Chim Acta 2001; 312: 227-229. (Pubitemid 32913602)
197. James SJ, Melnyk S, Jernigan S, Cleves MA, Halsted CH, Wong DH, Cutler P, Bock K, Boris M, Bradstreet JJ, Baker SM, Gaylor DW: Metabolic endophenotype and related genotypes are associated with oxidative stress in children with autism. Am J Med Genet B Neuropsychiatr Genet 2006; 141B:947-956. (Pubitemid 44905454)
198. James SJ, Rose S, Melnyk S, Jernigan S, Blossom S, Pavliv O, Gaylor DW: Cellular and mitochondrial glutathione redox imbalance in lymphoblastoid cells derived from children with autism. FASEB J 2009; 23: 2374-2383.
199. Geier DA, Kern JK, Garver CR, Adams JB, Audhya T, Nataf R, Geier MR: Biomarkers of environmental toxicity and susceptibility in autism. J Neurol Sci 2009; 280: 101-108.
200. Ming X, Johnson WG, Stenroos ES, Mars A, Lambert GH, Buyske S: Genetic variant of glutathione peroxidase 1 in autism. Brain Dev 2010; 32: 105-109.
201. Mutter J, Naumann J, Schneider R, Walach H, Haley B: Mercury and autism: accelerating evidence? Neuro Endocrinol Lett 2005; 26: 439-446.
202. Windham GC, Zhang L, Gunier R, Croen LA, Grether JK: Autism spectrum disorders in relation to distribution of hazardous air pollutants in the San Francisco bay area. Environ Health Perspect 2006; 114: 1438-1444. (Pubitemid 44314771)
203. Palmer RF, Blanchard S, Wood R: Proximity to point sources of environmental mercury release as a predictor of autism prevalence. Health Place 2009; 15: 18-24.
204. Valko M, Morris H, Cronin MT: Metals, toxicity and oxidative stress. Curr Med Chem 2005; 12: 1161-1208. (Pubitemid 40655271)
205. Junaid MA, Kowal D, Barua M, Pullarkat PS, Sklower Brooks S, Pullarkat RK: Proteomic studies identified a single nucleotide polymorphism in glyoxalase I as autism susceptibility factor. Am J Med Genet 2004; 131: 11-17. (Pubitemid 39434789)
206. Philippe A, Martinez M, Guilloud-Bataille M, Gillberg C, Rastam M, Sponheim E, Coleman M, Zappella M, Aschauer H, Van Maldergem L, Penet C, Feingold J, Brice A, Leboyer M: Genome-wide scan for autism susceptibility genes. Paris Autism Research International Sibpair Study. Hum Mol Genet 1999; 8: 805-812. (Pubitemid 29189047)
207. Yonan AL, Alarcon M, Cheng R, Magnusson PK, Spence SJ, Palmer AA, Grunn A, Juo SH, Terwilliger JD, Liu J, Cantor RM, Geschwind DH, Gilliam TC: A genomewide screen of 345 families for autism-susceptibility loci. Am J Hum Genet 2003; 73: 886-897. (Pubitemid 37271891)
208. El-Ansary A, Al-Daihan S, Al-Dbass A, Al-Ayadhi L: Measurement of selected ions related to oxidative stress and energy metabolism in Saudi autistic children. Clin Biochem 2010; 43: 63-70.
209. Yao Y, Walsh WJ, McGinnis WR, Pratico D: Altered vascular phenotype in autism: correlation with oxidative stress. Arch Neurol 2006; 63: 1161-1164. (Pubitemid 44232325)
210. De Felice C, Ciccoli L, Leoncini S, Signorini C, Rossi M, Vannuccini L, Guazzi G, Latini G, Comporti M, Valacchi G, Hayek J: Systemic oxidative stress in classic Rett syndrome. Free Radic Biol Med 2009; 47: 440-448.
211. Pratico D, Lawson JA, Rokach J, FitzGerald GA: The isoprostanes in biology and medicine. Trends Endocrinol Metab 2001; 12: 243-247. (Pubitemid 33714213)
212. Safai-Kutti S, Kutti J, Gillberg C: Impaired in vivo platelet reactivity in infantile autism. Acta Paediatr Scand 1985; 74: 799-800. (Pubitemid 15227562)
213. Safai-Kutti S, Denfors I, Kutti J, Wadenvik H: In vitro platelet function in infantile autism. Folia Haematol Int Mag Klin Morphol Blutforsch 1988; 115: 897-901.
214. Lucas SM, Rothwell NJ, Gibson RM: The role of inflammation in CNS injury and disease. Br J Pharmacol 2006; 147(suppl 1):S232-S240. (Pubitemid 43077281)
215. Patterson PH: Immune involvement in schizophrenia and autism: etiology, pathology and animal models. Behav Brain Res 2009; 204: 313-321.
216. Shi L, Smith SE, Malkova N, Tse D, Su Y, Patterson PH: Activation of the maternal immune system alters cerebellar development in the offspring. Brain Behav Immun 2009; 23: 116-123.
217. Shi L, Fatemi SH, Sidwell RW, Patterson PH: Maternal influenza infection causes marked behavioral and pharmacological changes in the offspring. J Neurosci 2003; 23: 297-302. (Pubitemid 36050430)
218. Machado ER, Carlos D, Lourenco EV, Souza GE, Sorgi CA, Silva EV, Ueta MT, Ramos SG, Aronoff DM, Faccioli LH: Cyclooxygenase- derived mediators regulate the immunological control of Strongyloides venezuelensis infection. FEMS Immunol Med Microbiol 2010; 59: 18-32.
219. Franco L, Talamini G: Cross-talk between inducible nitric oxide synthase and cyclooxygenase in Helicobacter-pylori -induced gastritis. Med Princ Pract 2009; 18: 477-481.
220. Chen D, Wei Y, Li X, Epstein S, Wolosin JM, Asbell P: Spla2-IIA is an inflammatory mediator when the ocular surface is compromised. Exp Eye Res 2009; 88: 880-888.
221. Figuero E, Carrillo-de-Albornoz A, Herrera D, Bascones-Martinez A: Gingival changes during pregnancy. I. Influence of hormonal variations on clinical and immunological parameters. J Clin Periodontol 2010; 37: 220-229.
222. Christiaens I, Zaragoza DB, Guilbert L, Robertson SA, Mitchell BF, Olson DM: Inflammatory processes in preterm and term parturition. J Reprod Immunol 2008; 79: 50-57.
223. Aisemberg J, Vercelli C, Wolfson M, Salazar AI, Osycka-Salut C, Billi S, Ribeiro ML, Farina M, Franchi AM: Inflammatory agents involved in septic miscarriage. Neuroimmunomodulation 2010; 17: 150-152.
224. Libbey JE, Sweeten TL, McMahon WM, Fujinami RS: Autistic disorder and viral infections. J Neurovirol 2005; 11: 1-10. (Pubitemid 40458366)
225. Comi AM, Zimmerman AW, Frye VH, Law PA, Peeden JN: Familial clustering of autoimmune disorders and evaluation of medical risk factors in autism. J Child Neurol 1999; 14: 388-394. (Pubitemid 29321099)
226. Enstrom AM, Van de Water JA, Ashwood P: Autoimmunity in autism. Curr Opin Investig Drugs 2009; 10: 463-473.
227. Licinio J, Alvarado I, Wong ML: Autoimmunity in autism. Mol Psychiatry 2002; 7: 329. (Pubitemid 34499351)
228. Li X, Chauhan A, Sheikh AM, Patil S, Chauhan V, Li XM, Ji L, Brown T, Malik M: Elevated immune response in the brain of autistic patients. J Neuroimmunol 2009; 207: 111-116.
229. Enstrom A, Krakowiak P, Onore C, Pessah IN, Hertz-Picciotto I, Hansen RL, Van de Water JA, Ashwood P: Increased IgG4 levels in children with autism disorder. Brain Behav Immun 2009; 23: 389-395.
230. Kawashti MI, Amin OR, Rowehy NG: Possible immunological disorders in autism: concomitant autoimmunity and immune tolerance. Egypt J Immunol 2006; 13: 99-104.
231. Meyer U, Nyffeler M, Engler A, Urwyler A, Schedlowski M, Knuesel I, Yee BK, Feldon J: The time of prenatal immune challenge determines the specificity of inflammation-mediated brain and behavioral pathology. J Neurosci 2006; 26: 4752-4762. (Pubitemid 44315314)
232. Parker-Athill EC, Tan J: Maternal immune activation and autism spectrum disorder: interleukin-6 signaling as a key mechanistic pathway. Neurosignals 2010, Epub ahead of print.
233. Atladottir HO, Thorsen P, Ostergaard L, Schendel DE, Lemcke S, Abdallah M, Parner ET: Maternal infection requiring hospitalization during pregnancy and autism spectrum disorders. J Autism Dev Disord 2010; 40: 1423-1430.
234. Singh VK, Jensen RL: Elevated levels of measles antibodies in children with autism. Pediatr Neurol 2003; 28: 292-294. (Pubitemid 36802229)
235. Chess S: Follow-up report on autism in congenital rubella. J Autism Child Schizophr 1977; 7: 69-81.
236. DeLong GR, Bean SC, Brown FR 3rd: Acquired reversible autistic syndrome in acute encephalopathic illness in children. Arch Neurol 1981; 38: 191-194. (Pubitemid 11137519)
237. Yamashita Y, Fujimoto C, Nakajima E, Isagai T, Matsuishi T: Possible association between congenital cytomegalovirus infection and autistic disorder. J Autism Dev Disord 2003; 33: 455-459. (Pubitemid 37127942)
238. Engman ML, Lewensohn-Fuchs I, Mosskin M, Malm G: Congenital cytomegalovirus infection: the impact of cerebral cortical malformations. Acta Paediatr 2010; 99: 1344-1349.
239. Lintas C, Altieri L, Lombardi F, Sacco R, Persico AM: Association of autism with polyomavirus infection in postmortem brains. J Neurovirol 2010; 16: 141-149.
240. Fatemi SH, Pearce DA, Brooks AI, Sidwell RW: Prenatal viral infection in mouse causes differential expression of genes in brains of mouse progeny: a potential animal model for schizophrenia and autism. Synapse 2005; 57: 91-99. (Pubitemid 40911524)
241. Fatemi SH, Reutiman TJ, Folsom TD, Huang H, Oishi K, Mori S, Smee DF, Pearce DA, Winter C, Sohr R, Juckel G: Maternal infection leads to abnormal gene regulation and brain atrophy in mouse offspring: implications for genesis of neurodevelopmental disorders. Schizophr Res 2008; 99: 56-70.
242. Ponzio NM, Servatius R, Beck K, Marzouk A, Kreider T: Cytokine levels during pregnancy influence immunological profiles and neurobehavioral patterns of the offspring. Ann N Y Acad Sci 2007; 1107: 118-128. (Pubitemid 47528788)
243. Hornig M, Weissenbock H, Horscroft N, Lipkin WI: An infection-based model of neurodevelopmental damage. Proc Natl Acad Sci USA 1999; 96: 12102-12107. (Pubitemid 29502865)
244. Fatemi SH, Halt AR, Realmuto G, Earle J, Kist DA, Thuras P, Merz A: Purkinje cell size is reduced in cerebellum of patients with autism. Cell Mol Neurobiol 2002; 22: 171-175.
245. Courchesne E, Carper R, Akshoomoff N: Evidence of brain overgrowth in the first year of life in autism. JAMA 2003; 290: 337-344. (Pubitemid 37430519)
246. Boddaert N, Zilbovicius M, Philipe A, Robel L, Bourgeois M, Barthelemy C, Seidenwurm D, Meresse I, Laurier L, Desguerre I, Bahi-Buisson N, Brunelle F, Munnich A, Samson Y, Mouren MC, Chabane N: MRI findings in 77 children with non-syndromic autistic disorder. PLoS One 2009; 4:e4415.
247. Brock TG, Peters-Golden M: Activation and regulation of cellular eicosanoid biosynthesis. ScientificWorldJournal 2007; 7: 1273-1284. (Pubitemid 47435440)
248. Wall R, Ross RP, Fitzgerald GF, Stanton C: Fatty acids from fish: the anti-inflammatory potential of long-chain omega-3 fatty acids. Nutr Rev 2010; 68: 280-289.
249. Legler DF, Bruckner M, Uetz-von Allmen E, Krause P: Prostaglandin E2 at new glance: novel insights in functional diversity offer therapeutic chances. Int J Biochem Cell Biol 2010; 42: 198-201.
250. Calder PC: Immunomodulation by omega-3 fatty acids. Prostaglandins Leukot Essent Fatty Acids 2007; 77: 327-335.
251. Yao C, Sakata D, Esaki Y, Li Y, Matsuoka T, Kuroiwa K, Sugimoto Y, Narumiya S: Prostaglandin E2-EP4 signaling promotes immune inflammation through TH1 cell differentiation and TH17 cell expansion. Nat Med 2009; 15: 633-640.
252. Harris SG, Padilla J, Koumas L, Ray D, Phipps RP: Prostaglandins as modulators of immunity. Trends Immunol 2002; 23: 144-150. (Pubitemid 34178297)
253. Croonenberghs J, Wauters A, Devreese K, Verkerk R, Scharpe S, Bosmans E, Egyed B, Deboutte D, Maes M: Increased serum albumin, gamma globulin, immunoglobulin IgG, and IgG2 and IgG4 in autism. Psychol Med 2002; 32: 1457-1463. (Pubitemid 35385656)
254. Trajkovski V, Ajdinski L, Spiroski M: Plasma concentration of immunoglobulin classes and subclasses in children with autism in the Republic of Macedonia: retrospective study. Croat Med J 2004; 45: 746-749. (Pubitemid 40052932)
255. Singh VK: Plasma increase of interleukin-12 and interferon-gamma. Pathological significance in autism. J Neuroimmunol 1996; 66: 143-145.
256. Jyonouchi H, Sun S, Itokazu N: Innate immunity associated with inflammatory responses and cytokine production against common dietary proteins in patients with autism spectrum disorder. Neuropsychobiology 2002; 46: 76-84. (Pubitemid 36151308)
257. Jyonouchi H, Geng L, Ruby A, Zimmerman-Bier B: Dysregulated innate immune responses in young children with autism spectrum disorders: their relationship to gastrointestinal symptoms and dietary intervention. Neuropsychobiology 2005; 51: 77-85. (Pubitemid 40522799)
258. Jyonouchi H, Sun S, Le H: Proinflammatory and regulatory cytokine production associated with innate and adaptive immune responses in children with autism spectrum disorders and developmental regression. J Neuroimmunol 2001; 120: 170-179. (Pubitemid 33016737)
259. Croonenberghs J, Bosmans E, Deboutte D, Kenis G, Maes M: Activation of the inflammatory response system in autism. Neuropsychobiology 2002; 45: 1-6. (Pubitemid 34117721)
260. Lee RH, Mills EA, Schwartz N, Bell MR, Deeg KE, Ruthazer ES, Marsh-Armstrong N, Aizenman CD: Neurodevelopmental effects of chronic exposure to elevated levels of pro-inflammatory cytokines in a developing visual system. Neural Dev 2010; 5: 2.
261. 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: 361-365. (Pubitemid 46873913)
262. 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. (Pubitemid 40053317)
263. Kim IJ, Beck HN, Lein PJ, Higgins D: Interferon gamma induces retrograde dendritic retraction and inhibits synapse formation. J Neurosci 2002; 22: 4530-4539. (Pubitemid 37465669)
264. Raymond GV, Bauman ML, Kemper TL: Hippocampus in autism: a Golgi analysis. Acta Neuropathol 1996; 91: 117-119.
265. 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: 664-673. (Pubitemid 40933118)
266. Ashwood P, Wakefield AJ: Immune activation of peripheral blood and mucosal CD3+ lymphocyte cytokine profiles in children with autism and gastrointestinal symptoms. J Neuroimmunol 2006; 173: 126-134.
267. White JF: Intestinal pathophysiology in autism. Exp Biol Med (Maywood) 2003; 228: 639-649.