Autism spectrum disorders are a group of neuro-developmental conditions characterized by varying degrees of language impairment, including verbal and non-verbal communication, impaired social skill, and repetitive behaviors. In this paper, we review the evidence for an association between autism and thiamine. A relationship between thiamine status and the development of autism has been established, with thiamine supplementation exhibiting a beneficial clinical effect on children with autism. Thiamine may involve in autism via apoptotic factors (transcription factor p53, Bcl-2, and caspase-3), neurotransmitter systems (serotonin, acetylcholine, and glutamate), and oxidative stress (prostaglandins, cyclooxygenase-2, reactive oxygen species, nitric oxide synthase, the reduced form of nicotinamide adenine dinucleotide phosphate, and mitochondrial dysfunction). In addition, thiamine has also been implicated in autism via its effects on basic myelin protein, glycogen synthetase kinase-3β, alpha-1 antitrypsin, and glyoxalase 1. Thiamine may play a role in children with autism. Additional investigation of thiamine in children with autism is needed.
Khanh vinh quốc Lương,
Lan Thi Hoàng Nguyễn,
The Role of Thiamine in Autism, American Journal of Psychiatry and Neuroscience.
Vol. 1, No. 2,
2013, pp. 22-37.
Aronson M, Hagberg B, Gillberg C:Attention deficits and autistic spectrum problems in children exposed to alcohol during gestation: a follow-up study.Dev Med Child Neurol 1997, 39:583-587.
Landgren M, Svensson L, Strömland K, Andersson Grönlund M: Prenatal alcohol exposure and neurodevelopmental disorders in children adopted from eastern Europe. Pediatrics 2010, 125:e1178-1185.
Tomasulo PA, Kater RMH, Iber FL: Impairment of thiamine absorption in alcoholism. Am J Clin Nutr 1968, 21:1340-1344.
Thomson AD, Baker H, Leevy CM: Pattern of 35 S-thiamine hydrochloride absorption in the malnourished alcoholic patient. J Lab Clin Med 1970, 76:34-45.
Ortega García JA, Angulo MG, Sobrino-Najul EJ, Soldin OP, Mira AP, Martínez-Salcedo E, Claudio L: Prenatal exposure of a girl with autism spectrum disorder to 'horsetail' (Equisetum arvense) herbal remedy and alcohol: a case report. J Med Case Reports 2011, 5:129.
Shamberger RJ. Autism rates associated with nutrition and the WIC program. J Am Coll Nutr 2011, 30:348-353.
Bell JM, Stewart CN: Effects of fetal and early postnatal thiamin deficiency on avoidance learning in rats. J Nutr 1979, 109:1577-1583.
Obrenovich ME, Shamberger RJ, Lonsdale D: Altered heavy metals and transketolase found in autistic spectrum disorder. Biol Trace Elem Res 2011, 144:475-486.
Raiten DJ, Massaro T, Zuckerman C: Vitamin and trace element assessment of autistic and learning disabled children. Nutr Behav 1984, 2:9-17.
Obrenovitch ME, Shamberger RJ, Londale D: Altered heavy metals and transketolase found in autistic spectrum disorder. Biol Trace Elem Res 2011, 144:475-486.
Lonsdale D, Shamberger RJ: Red cell transketolase as an indicator of nutritional deficiency. Am J Clin Nutr 1980, 33:205-211.
Fattal-Valevski A, Azouri-Fattal I, Greenstein YJ, Guindy M, Blau A, Zelnik N: Delayed language development due to infantile thiamine deficiency. Dev Med Child Neurol 2009, 51:629-634.
Bâ A: Functional vulnerability of developing central nervous system to maternal thiamine deficiencies in the rat. Dev Psychobiol 2005, 47:408-414.
Terasawa M, Nakahara T, Tsukada N, Sugawara A, Itokawa Y: The relationship between thiamine deficiency and performance of a learning task in rats. Metab Brain Dis 1999, 14:137-148.
Bâ A, N'Douba V, D'Almeida MA, Seri BV: Effects of maternal thiamine deficiencies on the pyramidal and granule cells of the hippocampus of rat pups. Acta Neurobiol Exp (Wars) 2005, 65:387-398.
Harrell RF: Mental response to added thiamine. J Nutr 1946, 31:283-298.
Hills JI, Golub MS, Bettendorff L, Keen CL: The effect of thiamin tetrahydrofurfuryl disulfide on behavior of juvenile DBA/2J mice. Neurotoxicol Teratol 2012, 34:242-252.
Lonsdale D, Shamberger RJ, Audhya T: Treatment of autism spectrum children with thiamine tetrahydrofurfuryl disulfide: a pilot study. Neuro Endocrinol Lett 2002, 23:303-308.
Araki N, Morimasa T, Sakai T, Tokuoh H, Yunoue S, Kamo M, Miyazaki K, Abe K, Saya H, Tsugita A: Comparative analysis of brain proteins from p53-deficient mice by two-dimensional electrophoresis. Electrophoresis 2000, 21:1880-1889.
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.
Fatemi SH, Halt AR: Altered levels of Bcl2 and p53 proteins in parietal cortex reflect deranged apoptotic regulation in autism. Synapse 2001, 42:281-284.
Araghi-Niknam M, Fatemi SH: Levels of Bcl-2 and P53 are altered in superior frontal and cerebellar cortices of autistic subjects. Cell Mol Neurobiol 2003, 23:945-952.
Sheikh AM, Malik M, Wen G, Chauhan A, Chauhan V, Gong CX, Liu F, Brown WT, Li X: BDNF-Akt-Bcl2 antiapoptotic signaling pathway is compromised in the brain of autistic subjects. J Neurosci Res 2010, 88:2641-2647.
Lo PK, Chen JY, Tang PP, Lin J, Lin CH, Su LT, Wu CH, Chen TL, Yang Y, Wang FF: Identification of a mouse thiamine transporter gene as a direct transcriptional target for p53. J Biol Chem 2001, 276:37186-37193.
McLure KG, Takagi M, Kastan MB: NAD+ modulates p53 DNA binding specificity and function. Mol Cellular Biol 2004, 24:9958-9967.
Yang Z, Ge J, Yin W, Shen H, Liu H, Guo Y: The expression of p53, MDM2 and Ref1 gene in cultured retina neurons of SD rats treated with vitamin B1 and/or elevated pressure. Yan Ke Xue Bao 2004, 20:259-263. [Article in Chinese]
Sasaki T, Kitagawa K, Yagita Y, Sugiura S, Omura-Matsuoka E, Tanaka S, Matsushita K, Okano H, Tsujimoto Y, Hori M: Bcl2 enhances survival of newborn neurons in the normal and ischemic hippocampus. J Neurosci Res 2006, 84:1187-1196.
Jarskog LF, Gilmore JH. Developmental expression of Bcl-2 protein in human cortex. Brain Res Dev Brain Res 2000, 119:225-230.
Shimohama S, Fujimoto S, Sumida Y, Tanino H: Differential expression of rat brain bcl-2 family proteins in development and aging. Biochem Biophys Res Commun 1998, 252:92-96.
Zhong LT, Sarafian T, Kane DJ, Charles AC, Mah SP, Edwards RH, Bredesen DE: bcl-2 inhibits death of central neural cells induced by multiple agents. Proc Natl Acad Sci U S A 1993, 90:4533-4537.
Ritvo ER, Freeman BJ, Scheibel AB, Duong T, Robinson H, Guthrie D, Ritvo A: Lower Purkinje cell counts in the cerebella of four autistic subjects: initial findings of the UCLA-NSAC Autopsy Research Report. Am J Psychiatry 1986, 143:862-866.
Ghanizadeh A: Malondialdehyde, Bcl-2, Superoxide Dismutase and Glutathione Peroxidase may Mediate the Association of Sonic Hedgehog Protein and Oxidative Stress in Autism. Neurochem Res 2012, 37:899-901.
Fatemi SH, Stary JM, Halt AR, Realmuto GR: Dysregulation of Reelin and Bcl-2 proteins in autistic cerebellum. J Autism Dev Disord 2001, 31:529-535.
Malik M, Sheikh AM, Wen G, Spivack W, Brown WT, Li X: Expression of inflammatory cytokines, Bcl2 and cathepsin D are altered in lymphoblasts of autistic subjects. Immunobiology 2011, 216:80-85.
Nguyen A, Rauch TA, Pfeifer GP, Hu VW: Global methylation profiling of lymphoblastoid cell lines reveals epigenetic contributions to autism spectrum disorders and a novel autism candidate gene, RORA, whose protein product is reduced in autistic brain. FASEB J 2010, 24:3036-3051.
Rabie T, Mühlhofer W, Bruckner T, Schwab A, Bauer AT, Zimmermann M, Bonke D, Marti HH, Schenkel J: Transient protective effect of B-vitamins in experimental epilepsy in the mouse brain. J Mol Neurosci 2010, 41:74-79.
Ishaque A, Al-Rubeai M: Role of vitamins in determining apoptosis and extent of suppression by bcl-2 during hybridoma cell culture. Apoptosis 2002, 7:231-239.
Katare R, Caporali A, Emanueli C, Madeddu P: Benfotiamine improves functional recovery of the infarcted heart via activation of pro-survival G6PD/Akt signaling pathway and modulation of neurohormonal response. J Mol Cell Cardiol 2010, 49:625-638.
Beltramo E, Berrone E, Tarallo S, Porta M: Different apoptotic responses of human and bovine pericytes to fluctuating glucose levels and protective role of thiamine. Diabetes Metab Res Rev 2009, 25:566-576.
Salvesen GS, Riedl SJ. Caspase mechanisms. Adv Exp Med Biol 2008, 615:13-23.
Satomoto M, Satoh Y, Terui K, Miyao H, Takishima K, Ito M, Imaki J: Neonatal exposure to sevoflurane induces abnormal social behaviors and deficits in fear conditioning in mice. Anesthesiology 2009, 110:628-637.
Sheikh AM, Li X, Wen G, Tauqeer Z, Brown WT, Malik M: Cathepsin D and apoptosis related proteins are elevated in the brain of autistic subjects. Neuroscience 2010, 165:363-370.
Siniscalco D, Sapone A, Giordano C, Cirillo A, de Novellis V, de Magistris L, Rossi F, Fasano A, Maione S, Antonucci N: The Expression of Caspases is Enhanced in Peripheral Blood Mononuclear Cells of Autism Spectrum Disorder Patients. J Autism Dev Disord 2012, 42:1403-1410.
Liu S, Huang H, Lu X, Golinski M, Comesse S, Watt D, Grossman RB, Moscow JA: Down-regulation of thiamine transporter THTR2 gene expression in breast cancer and its association with resistance to apoptosis. Mol Cancer Res 2003, 1:665-673.
Chornyy S, Parkhomenko J, Chorna N: Thiamine deficiency caused by thiamine antagonists triggers upregulation of apoptosis inducing factor gene expression and leads to caspase 3-mediated apoptosis in neuronally differentiated rat PC-12 cells. Acta Biochim Pol 2007, 54:315-522.
Gadau S, Emanueli C, Van Linthout S, Graiani G, Todaro M, Meloni M, Campesi I, Invernici G, Spillmann F, Ward K, Madeddu P: Benfotiamine accelerates the healing of ischaemic diabetic limbs in mice through protein kinase B/Akt-mediated potentiation of angiogenesis and inhibition of apoptosis. Diabetologia 2006, 49:405-420.
Kang KD, Majid AS, Kim KA, Kang K, Ahn HR, Nho CW, Jung SH: Sulbutiamine counteracts trophic factor deprivation induced apoptotic cell death in transformed retinal ganglion cells. Neurochem Res 2010, 35:1828-1839.
McDougle CJ, Naylor ST, Cohen DJ, Aghajanian GK, Heninger GR, Price LH: Effects of tryptophan depletion in drug-free adults with autistic disorder. Arch Gen Psychiatry 1996, 53:993-1000.
Kolevzon A, Mathewson KA, Hollander E. Selective serotonin reuptake inhibitors in autism: a review of efficacy and tolerability. J Clin Psychiatry 2006, 67:407-414.
Chugani DC, Muzik O, Rothermel R, Behen M, Chakraborty P, Mangner T, da Silva EA, Chugani HT: Altered serotonin synthesis in the dentatothalamocortical pathway in autistic boys. Ann Neurol 1997, 42:666-669.
de Villard R, Flachaire E, Thoulon JM, Dalery J, Maillet J, Chauvin C, Quincy C, Renaud B: Platelet serotonin concentrations in autistic children and members of their families. Encephale 1986, 12:139-142. [Article in French]
Anderson GM, Horne WC, Chatterjee D, Cohen DJ: The hyperserotonemia of autism. Ann N Y Acad Sci 1990, 600:331-340.
Azmitia EC, Singh JS, Whitaker-Azmitia PM: Increased serotonin axons (immunoreactive to 5-HT transporter) in postmortem brains from young autism donors. Neuropharm 2011, 60:1347-1354
Chamberlain RS, Herman BH: A novel biochemical model linking dysfunctions in brain melatonin, proopiomelanocortin peptides, and serotonin in autism. Biol Psych 1990, 28:773-793.
Cuccaro ML, Wright HH, Abramson RK, Marsteller FA, Valentine J: Whole-blood serotonin and cognitive functioning in autistic individuals and their first-degree relatives. Neuropsychiatry Clin Neurosci 1993, 5:94-101.
McBride PA, Anderson GM, Hertzig ME, Snow ME, Thompson SM, Khait VD, Shapiro T, Cohen DJ: Effects of diagnosis, race, and puberty on platelet serotonin levels in autism and mental retardation. J Am Acad Child Adolesc Psych 1998, 37:767-776.
Marazziti D, Muratori F, Cesari A, Masala I, Baroni S, Giannaccini G, Dell'Osso L, Cosenza A, Pfanner P, Cassano GB: Increased density of the platelet serotonin transporter in autism. Pharmacopsychiatry 2000, 33:165-168.
Anderson BM, Schnetz-Boutaud NC, Bartlett J, Wotawa AM, Wright HH, Abramson RK, Cuccaro ML, Gilbert JR, Pericak-Vance MA, Haines JL: Examination of association of genes in the serotonin system to autism. Neurogenetics 2009, 10:209-216.
Arieff Z, Kaur M, Gameeldien H, van der Merwe L, Bajic VB: 5-HTTLPR polymorphism: analysis in South African autistic individuals. Hum Biol 2010, 82:291-300.
Koishi S, Yamamoto K, Matsumoto H, Koishi S, Enseki Y, Oya A, Asakura A, Aoki Y, Atsumi M, Iga T, Inomata J, Inoko H, Sasaki T, Nanba E, Kato N, Ishii T, Yamazaki K: Serotonin transporter gene promoter polymorphism and autism: a family-based genetic association study in Japanese population. Brain Dev 2006, 28:257-260.
Conroy J, Meally E, Kearney G, Fitzgerald M, Gill M, Gallagher L: Serotonin transporter gene and autism: a haplotype analysis in an Irish autistic population. Mol Psych 2004, 9:587-593.
Longo D, Schüler-Faccini L, Brandalize AP, dos Santos Riesgo R, Bau CH: Influence of the 5-HTTLPR polymorphism and environmental risk factors in a Brazilian sample of patients with autism spectrum disorders. Brain Res 2009, 1267:9-17.
Wu S, Guo Y, Jia M, Ruan Y, Shuang M, Liu J, Gong X, Zhang Y, Yang J, Yang X, Zhang D: Lack of evidence for association between the serotonin transporter gene (SLC6A4) polymorphisms and autism in the Chinese trios. Neurosci Lett 2005, 381:1-5.
Veenstra-VanderWeele J, Muller CL, Iwamoto H, Sauer JE, Owens WA, Shah CR, Cohen J, Mannangatti P, Jessen T, Thompson BJ, Ye R, Kerr TM, Carneiro AM, Crawley JN, Sanders-Bush E, McMahon DG, Ramamoorthy S, Daws LC, Sutcliffe JS, Blakely RD: Autism gene variant causes hyperserotonemia, serotonin receptor hypersensitivity, social impairment and repetitive behavior. Proc Natl Acad Sci U S A 2012, 109:5469-5474.
Chan-Palay V, Plaitakis A, Nicklas W, Berl S: Autoradiographic demonstration of loss of labeled indoleamine axons of the cerebellum in chronic diet-induced thiamine deficiency. Brain Res 1977, 138:380-384.
Murata A, Nakagawasai O, Yamadera F, Oba A, Wakui K, Arai Y, Tadano T: Dysfunction of serotonergic systems in thiamine-deficient diet fed mice: effects of SSRI on abnormality induced by thiamine deficiency. Nihon Shinkei Seishin Yakurigaku Zasshi 2004, 24:93-99 [Article in Japanese]
Botez MI, Young SN, Bachevalier J, Gauthier S: Thiamine deficiency and cerebrospinal fluid 5-hydroxyindoleacetic acid: a preliminary study. J Neurol Neurosurg Psychiatry 1982, 45:731-733.
Plaitakis A, Nicklas WJ, Berl S:Thiamine deficiency: selective impairment of the cerebellar serotonergic system. Neurology 1978, 28:691-698.
Van Woert MH, Plaitakis A, Hwang EC, Berl S: Effect of thiamine deficiency on brain serotonin turnover. Brain Res 1979, 179:103-110.
Keating E, Lemos C, Monteiro R, Azevedo I, Martel F: The effect of a series of organic cations upon the plasmalemmal serotonin transporter, SERT.Life Sci 2004, 76:103-119.
Le Marec N, Hébert C, Botez MI, Botez-Marquard T, Marchand L, Reader TA: Serotonin innervation of Lurcher mutant mice: basic data and manipulation with a combination of amantadine, thiamine and L-tryptophan. Brain Res Bull 1999, 48:195-201.
Perry EK, Lee ML, Martin-Ruiz CM, Court JA, Volsen SG, Merrit J, Folly E, Iversen PE, Bauman ML, Perry RH, Wenk GL: Cholinergic activity in autism: abnormalities in the cerebral cortex and basal forebrain. Am J Psychiatry 2001, 158:1058-1066.
Lee M, Martin-Ruiz C, Graham A, Court J, Jaros E, Perry R, Iversen P, Bauman M, Perry E: Nicotinic receptor abnormalities in the cerebellar cortex in autism. Brain 2002, 125:1483-1495.
Martin-Ruiz CM, Lee M, Perry RH, Baumann M, Court JA, Perry EK: Molecular analysis of nicotinic receptor expression in autism. Brain Res Mol Brain Res 2004, 123:81-90.
Hardan AY, Handen BL: A retrospective open trial of adjunctive donepezil in children and adolescents with autistic disorder. J Child Adolesc Psychopharmacol 2002, 12:237-241.
Chez MG, Aimonovitch M, Buchanan T, Mrazek S, Tremb RJ: Treating autistic spectrum disorders in children: utility of the cholinesterase inhibitor rivastigmine tartrate. J Child Neurol 2004, 19:165-169.
Ruenwongsa P, Pattanavibag S: Impairment of acetylcholine synthesis in deficient rats developed by prolonged tea consumption. Life Sci 1984, 34:365-370.
Vorhees CV, Schmidt DE, Barrett RJ: Effects of pyrithiamin on acetylcholine levels and utilization in rat brain. Brain Res Bull 1978, 3:493-496.
Meador KJ, Nichols ME, Franke P, Durkin MW, Oberzan RL, Moore EE, Loring DW: Evidence for a central cholinergic effect of high-dose thiamine. Ann Neurol 1993, 34:724-726.
Barclay LL, Gibson GE, Blass JP: Impairment of behavior and acetylcholine metabolism in thiamine deficiency. J Pharmacol Exp Ther 1981, 217:537-543.
Squire LR, Zola-Morgan S: The medial temporal lobe memory system. Science 1991, 253:1380-1386.
Bauman ML, Kemper TL: Neuroanatomic observations of the brain in autism: a review and future directions. Int J Dev Neurosci 2005, 23:183-187.
Raymond GV, Bauman ML, Kemper TL: Hippocampus in autism: a Golgi analysis.Acta Neuropathol1996, 91:117-119.
Fatemi SH, Halt AR, Stary JM, Kanodia R, Schulz SC, Realmuto GR: Glutamic acid decarboxylase 65 and 67 kDa proteins are reduced in autistic parietal and cerebellar cortices. Biol Psychiatry 2002, 52:805-810.
Brown MS, Singel D, Hepburn S, Rojas DC: Increased Glutamate Concentration in the Auditory Cortex of Persons With Autism and First-Degree Relatives: A (1) H-MRS Study. Autism Res 2013, 6:1-10.
Kubas B, Kułak W, Sobaniec W, Tarasow E, Lebkowska U, Walecki J: Metabolite alterations in autistic children: a 1H MR spectroscopy study. Adv Med Sci 2012, 57:152-156.
Yadav R, Gupta SC, Hillman BG, Bhatt JM, Stairs DJ, Dravid SM: Deletion of glutamate delta-1 receptor in mouse leads to aberrant emotional and social behaviors. PLoS One 2012, 7:e32969.
Rout UK, Mungan NK, Dhossche DM: Presence of GAD65 autoantibodies in the serum of children with autism or ADHD. Eur Child Adolesc Psychiatry 2012, 21:141-147.
Silverman JM, Buxbaum JD, Ramoz N, Schmeidler J, Reichenberg A, Hollander E, Angelo G, Smith CJ, Kryzak LA: Autism-related routines and rituals associated with a mitochondrial aspartate/glutamate carrier SLC25A12 polymorphism. Am J Med Genet B Neuropsychiatr Gene 2008, 147:408-410.
Turunen JA, Rehnström K, Kilpinen H, Kuokkanen M, Kempas E, Ylisaukko-Oja T: Mitochondrial aspartate/glutamate carrier SLC25A12 gene is associated with autism. Autism Res 2008, 1:189-192.
Hazell AS, Pannunzio P, Rama Rao KV, Pow DV, Rambaldi A: Thiamine deficiency results in downregulation of the GLAST glutamate transporter in cultured astrocytes. Glia 2003, 43:175-184.
Karuppagounder SS, Xu H, Shi Q, Chen LH, Pedrini S, Pechman D, Baker H, Beal MF, Gandy SE, Gibson GE: Thiamine deficiency induces oxidative stress and exacerbates the plaque pathology in Alzheimer’s mouse model. Neurobiol Aging 2009, 30:1587-1600.
Hazell AS, Rao KV, Danbolt NC, Pow DV, Butterworth RF: Selective down-regulation of the astrocyte glutamate transporters GLT-1 and GLAST within the medial thalamus in experimental Wernicke's encephalopathy. J Neurochem 2001, 78:560-568.
Tassoni D, Kaur G, Weisinger RS, Sinclair AJ: The role of eicosanoids in the brain. Asia Pac J Clin Nutr 2008, 17:220-228.
Tamiji J, Crawford DA: Prostaglandin E2 and misoprostol induce neurite retraction in Neuro-2a cells. Biochem Biophys Res Commun 2010, 398:450-456.
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.
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 2009, 62:66-69.
Gu B, Desjardins P, Butterworth RF: Selective increase of neuronal cyclooxygenase-2 (COX-2) expression in vulvenerable brain regions of rats with experimental Wernicke’s encephalopathy: effect of numesulide. Metab Brain Dis 2008, 23:175-187.
Yaday UC, Subramanyam S, Ramana KV: Prevention of endotoxin-induced uveitis in rats by benfotiamine, a lipophilic analogue of vitamin B1. Invest Ophthalmol Vis Sci 2009, 50:2276-2282.
Yaday UC, Kalariya NM, Srivastava SK, Ramana KV: Protective role of benfotiamine, a fat-soluble vitamin B1 analogue, in lipopolysaccharide-induced cytotoxic signals in murine macrophages. Free Radic Biol Med 2010, 48:1423-1434.
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.
González-Fraguela M, Hung M, Vera H, Maragoto C, Noris E. Blanco L Galvizu R, Robinson, M: Oxidative stress markers in children with autism spectrum disorders. British J Med Medical Res 2013, 3:307-317.
Sajdel-Sulkowska E, Lipinski B, Windom H, Audhya J, McGinnis W: Oxidative stress in autism: cerebellar 3 nitrotyrosine levels. Am J Biochem Biotechnol 2008, 4:73-84.
Rose S, Melnyk S, Pavliv O, Bai S, Nick TG, Frye RE, James SJ: Evidence of oxidative damage and inflammation associated with low glutathione redox status in the autism brain. Transl Psychiatry 2012, 2:e134
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.
Yao Y, Walsh WJ, McGinnis WR, Praticò D: Altered vascular phenotype in autism: correlation with oxidative stress. Arch Neurol 2006, 63:1161-1164.
Giulivi C, Zhang YF, Omanska-Klusek A, Ross-Inta C, Wong S, Hertz-Picciotto I, Tassone F, Pessah IN:Mitochondrial dysfunction in autism. JAMA 2010, 304:2389-2396.
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.
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, 42:1032-1040.
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.
Essa MM, Guillemin GJ, Waly MI, Al-Sharbati MM, Al-Farsi YM, Hakkim FL, Ali A, Al-Shafaee MS: Increased Markers of Oxidative Stress in Autistic Children of the Sultanate of Oman. Biol Trace Elem Res 2012, 147:25-27.
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.
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, 3:132-143.
Williams TA, Mars AE, Buyske SG, Stenroos ES, Wang R, Factura-Santiago MF, Lambert GH, Johnson WG: Risk of autistic disorder in affected offspring of mothers with a glutathione S-transferase P1 haplotype. Arch Pediatr Adolesc Med 2007, 161:356-361.
Frustaci A, Neri M, Cesario A, Adams JB, Domenici E, Dalla Bernardina B, Bonassi S: Oxidative stress-related biomarkers in autism: systematic review and meta-analyses. Free Radic Biol Med 2012, 52:2128-2141.
Calingasan NY, Chun WJ, Park LC, Gibson GE: Oxidative stress is associated with region-specific neuronal death during thiamine deficiency. J Neuropathol Exp Neurol 1999, 58:946-958.
Lukienko PI, Mel’nichenko NG, Zverinskii IV, Zabrodskaya SV: Antioxidant properties of thiamine. Bull Exp Biol Med 2000, 130:874-876.
Portari GV, Marchini JS, Vannucchi H, Jordao AA: Antioxidant effect of thiamine on acutely alcoholized rats and lack of efficacy using thiamine or glucose to reduce blood alcohol content. Basic Clin Pharmacol Toxicol 2008, 103:482-486.
Park DJ, West AR: Regulation of striatal nitric oxide synthesis by local dopamine and glutamate interactions. J Neurochem 2009, 111:1457-1465.
West AR, Galloway MP, Grace AA: Regulation of striatal dopamine neurotransmission by nitric oxide: effector pathways and signaling mechanisms. Synapse 2002, 44:227-245.
Söğüt S, Zoroğlu SS, Ozyurt H, Yilmaz HR, Ozuğurlu F, Sivasli E, Yetkin O, Yanik M, Tutkun H, Savaş HA, Tarakçioğlu M, Akyol O: Changes in nitric oxide levels and antioxidant enzyme activities may have a role in the pathophysiological mechanisms involved in autism. Clin Chim Acta 2003, 331:111-117.
Lakshmi Priya MD, Geetha A: A biochemical study on the level of proteins and their percentage of nitration in the hair and nail of autistic children. Clin Chim Acta 2011, 412:1036-1042.
Kim HW, Cho SC, Kim JW, Cho IH, Kim SA, Park M, Cho EJ, Yoo HJ: Family-based association study between NOS-I and -IIA polymorphisms and autism spectrum disorders in Korean trios. Am J Med Genet B Neuropsychiatr Genet 2009, 150B:300-306.
Fillano JJ, Goldenthal MJ, Rhodes CH, Marin-Garcia J: Mitochondrial dysfunction in patients with hypotonia, epilepsy, autism, and developmental delay: HEADD syndrome. J Child Neurol 2002, 17:435-439.
Oliveira G, Diogo L, Grazina M, Garcia P, Ataíde A, Marques C, Miguel T, Borges L, Vicente AM, Oliveira CR: Mitochondrial dysfunction in autism spectrum disorders: a population-based study. Dev Med Child Neurol 2005, 47:185-189.
Jacobia SJ, Korotchkina LG, Patel MS: Characterization of a missense mutation at histidine-44 in a pyruvate dehydrogenase-deficient patient. Biochim Biophys Acta 2002, 1586:32-42.
Naito E, Ito M, Takeda E, Yokota I, Yoshijima S, Kuroda Y: Molecular analysis of abnormal pyruvate dehydrogenase in a patient with thiamine-responsive congenital lactic academia. Pediatr Res 1994, 36:340-346.
Naito E, Ito M, Yokota I, Saijo T, Matsuda J, Ogawa Y, Kitamura S, Takada E, Horii Y, Kuroda Y: Thiamine-responsive pyruvate dehydrogenase deficiency in two patients caused by a point mutation (F205L and L216F) within the thiamine pyrophosphate pyrophosphate binding region. Biochim Biophys Acta 2002, 1588:79-84.
Bonne G, Benelli C, De Meirleir L, Lissens W, Chaussain M, Diry M, Clot JP, Ponsot G, Geoffroy V, Leroux JP, Marsac C: E1 pyruvate dehydrogenase deficiency in a child with motor neuropathy. Pediatr Res 1993, 33:284-288.
Meléndez RR: Importance of water-soluble vitamins as regulatory factors of genetic expression. Rev Invest Clin 2002, 54:77-83. [Article in Spanish]
Martin P, Singleton CK, Hiller-Stumhöfel S: The role of thiamine deficiency in alcoholic brain disease. Alcohol Res Health 2003, 27:174-181.
Ishii K, Sarai K, Sanemori H, Kawasaki T: Concentration of thiamine and its phosphate esters in rat tissues determined by high pressure liquid chromography. J Nutr Sci Vitaminol (Tokyo) 1979, 25:517-523.
Bubber P, Ke ZJ, Gibson GE: Tricarboxylic acid cycle enzymes following thiamine deficiency. Neurochem Int 2004, 45:1021-1028.
Adams JB, Audhya T, McDonough-Means S, Rubin RA, Quig D, Geis E, Gehn E, Loresto M, Mitchell J, Atwood S, Barnhouse S, Lee W: Nutritional and metabolic status of children with autism vs. neurotypical children, and the association with autism severity. Nutr Metab (Lond) 2011, 8:34.
Adams JB, Audhya T, McDonough-Means S, Rubin RA, Quig D, Geis E, Gehn E, Loresto M, Mitchell J, Atwood S, Barnhouse S, Lee W: Effect of a vitamin/mineral supplement on children and adults with autism. BMC Pediatr 2011, 11:111.
Marui T, Funatogawa I, Koishi S, Yamamoto K, Matsumoto H, Hashimoto O, Jinde S, Nishida H, Sugiyama T, Kasai K, Watanabe K, Kano Y, Kato N: The NADH-ubiquinone oxidoreductase 1 alpha subcomplex 5 (NDUFA5) gene variants are associated with autism. Acta Psychiatr Scand 2011, 123:118-124.
Shangari N, Mehta R, O'brien PJ: Hepatocyte susceptibility to glyoxal is dependent on cell thiamin content. Chem Biol Interact 2007, 165:146-154.
Galdhar NR, Pawar SS: Hepatic drug metabolism and lipid peroxidation in thiamine deficient rats. Int J Vitam Nutr Res 1976, 46:14-23.
Fraser DA, Hessvik NP, Nikolić N, Aas V, Hanssen KF, Bøhn SK, Thoresen GH, Rustan AC: Benfotiamine increases glucose oxidation and downregulates NADPH oxidase 4 expression in cultured human myotubes exposed to both normal and high glucose concentrations. Genes Nutr 2012, 7:459-469.
Grosse W 3rd, Wade AE: The effect of thiamine consumption on liver microsomal drug-metabolizing pathways. J Pharmacol Exp Ther 1971, 176:758-765.
Singh VK, Warren RP, Odell JD, Warren WL, Cole P: Antibodies to myelin basic protein in children with autistic behavior. Brain Behav Immun 1993, 7:97-103.
Singh VK, Warren R, Averett R, Ghaziuddin M: Circulating autoantibodies to neuronal and glial filament proteins in autism. Pediatr Neurol 1997, 17:88-90.
Stephenson DT, O'Neill SM, Narayan S, Tiwari A, Arnold E, Samaroo HD, Du F, Ring RH, Campbell B, Pletcher M, Vaidya VA, Morton D: Histopathologic characterization of the BTBR mouse model of autistic-like behavior reveals selective changes in neurodevelopmental proteins and adult hippocampal neurogenesis. Mol Autism 2011, 2:7.
Gozzi M, Nielson DM, Lenroot RK, Ostuni JL, Luckenbaugh DA, Thurm AE, Giedd JN, Swedo SE: A magnetization transfer imaging study of corpus callosum myelination in young children with autism. Biol Psychiatry 2012, 72:215-220.
Mostafa GA, Al-Ayadhi LY: A lack of association between hyperserotonemia and the increased frequency of serum anti-myelin basic protein auto-antibodies in autistic children. J Neuroinflammation 2011, 8:71.
Markham JA, Herting MM, Luszpak AE, Juraska JM, Greenough WT: Myelination of the corpus callosum in male and female rats following complex environment housing during adulthood. Brain Res 2009, 1288:9-17.
Mostafa GA, El-Sayed ZA, El-Aziz MM, El-Sayed MF: Serum anti-myelin-associated glycoprotein antibodies in Egyptian autistic children. J Child Neurol 2008, 23:1413-1438.
Singer HS, Morris CM, Gause CD, Gillin PK, Crawford S, Zimmerman AW: Antibodies against fetal brain in sera of mothers with autistic children. J Neuroimmunol 2008, 194:165-172.
Martin I, Gauthier J, D'Amelio M, Védrine S, Vourc'h P, Rouleau GA, Persico AM, Andres CR: Transmission disequilibrium study of an oligodendrocyte and myelin glycoprotein gene allele in 431 families with an autistic proband. Neurosci Res 2007, 59:426-430.
Castellano B, Gonzalez B, Palacios G: Cytochemical demonstration of TPPase in myelinated fibers in the central and peripheral nervous system of the rat. Brain Res 1989, 492:203-210.
Ishibashi S, Yokota T, Shiojiri T, Matunaga T, Tanaka H, Nishina K, Hirota H, Inaba A, Yamada M, Kanda T, Mizusawa H: Reversible acute axonal polyneuropathy associated with Wernicke-Korsakoff syndrome: impaired physiological nerve conduction due to thiamine deficiency? J Neurol Neurosurg Psychiatry 2003, 74:674-676.
Gui QP, Zhao WQ, Wang LN: Wernicke's encephalopathy in nonalcoholic patients: clinical and pathologic features of three cases and literature reviewed. Neuropathology 2006, 26:231-235.
Jiang H, Guo W, Liang X, Rao Y: Both the establishment and the maintenance of neuronal polarity require active mechanisms: critical roles of GSK-3beta and its upstream regulators. Cell 2005, 120:123-135.
Yuskaitis CJ, Beurel E, Jope RS: 1. Evidence of reactive astrocytes but not peripheral immune system activation in a mouse model of Fragile X syndrome. Biochim Biophys Acta. 2010, 1802:1006-1012.
Min WW, Yuskaitis CJ, Yan Q, Sikorski C, Chen S, Jope RS, Bauchwitz RP: Elevated glycogen synthase kinase-3 activity in Fragile X mice: key metabolic regulator with evidence for treatment potential. Neuropharmacology 2009, 56:463-472.
Mines MA, Yuskaitis CJ, King MK, Beurel E, Jope RS: GSK3 influences social preference and anxiety-related behaviors during social interaction in a mouse model of fragile X syndrome and autism. PLoS One 2010, 5:e9706.
Beaulieu JM, Zhang X, Rodriguiz RM, Sotnikova TD, Cools MJ, Wetsel WC, Gainetdinov RR, Caron MG: Role of GSK3 beta in behavioral abnormalities induced by serotonin deficiency. Proc Natl Acad Sci U S A 2008, 105:1333-1338.
Ciani L, Salinas PC: WNTs in the vertebrate nervous system: from patterning to neuronal connectivity. Nat Rev Neurosci 2005, 6:351-362.
Zhang Y, Sun Y, Wang F, Wang Z, Peng Y, Li R:Downregulating the Canonical Wnt/β-catenin Signaling Pathway Attenuates the Susceptibility to Autism-like Phenotypes by Decreasing Oxidative Stress. Neurochem Res 2012, 37:1409-1419
Zhao J, Sun X, Yu Z, Pan X, Gu F, Chen J, Dong W, Zhao L, Zhong C: Exposure to pyrimidine increases beta-amyloid accumulation, Tau hyperphosphorylation, and glycogen synthetase kinase-3 activity in the brain. Neurotox Res 2010, 19:575-583.
Pan X, Gong N, Zhao J, Yu Z, Gu F, Chen J, Sun X, Zhao L, Yu M, Xu Z, Dong W, Qin Y, Fei G, Zhong C, Xu TL: Powerful beneficial effects of benfotiamine on cognitive impairment and beta-amyloid deposition in amyloid precursor protein/presenilin-1 transgenic mice. Brain 2010, 133:1342-1351.
Walker-Smith J, Andrews J. Alpha-1-antitrypsin, autism, and coeliac disease: Lancet 1972, 2:883-884.
Russo AJ, Neville L, Wroge C: Low Serum Alpha-1 Antitrypsin (AAT) in Family Members of Individuals with Autism Correlates with PiMZ Genotype. Biomark Insights 2009, 4:45-56.
Ali BH: Some pharmacological and toxicological properties of furazolidone.Vet Res Commun 1983, 6:1-11.
Ali BH, Bartlet AL: Anorexia and antagonism of thiamin utilization in poultry treated with furazolidone. Q J Exp Physiol 1982, 67:437-448.
Staley NA, Noren GR, Bandt CM, Sharp HL: Furazolidone-induced cardiomyopathy in turkeys. Association with a relative alpha1-antitrypsin deficiency. Furazolidone-induced cardiomyopathy in turkeys. Association with a relative alpha1-antitrypsin deficiency. Am J Pathol 1978, 91:531-544.
Ali BH, Hassan T, Wasfi IA, Mustafa AI: Toxicity of furazolidone to Nubian goats. Vet Hum Toxicol 1984, 26:197-200.
Czarnecki C: Cardiomyopathy in turkeys. Comp Biochem Physiol A Comp Physiol. 1984, 77:591-598.
Martin J, Hadchouel M, Gaultier M, Luzeau R, Hugon R, Daguet J: An animal model for the study of human alpha-1-antitrypsin deficiency. Biomedicine 1976, 25:319-320.
Schmechel DE: Art, alpha-1-antitrypsin polymorphisms and intense creative energy: blessing or curse? Neurotoxicology 2007, 28:899-914.
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 A 2004, 131:11-17.
Barua M, Jenkins EC, Chen W, Kuizon S, Pullarkat RK, Junaid MA: Glyoxalase I polymorphism rs2736654 causing the Ala111Glu substitution modulates enzyme activity--implications for autism. Autism Res 2011, 4:262-270.
Boso M, Emanuele E, Minoretti P, Arra M, Politi P, Ucelli di Nemi S, Barale F: Alterations of circulating endogenous secretory RAGE and S100A9 levels indicating dysfunction of the AGE-RAGE axis in autism. Neurosci Lett 2006, 410:169-173.
Bierhaus A, Humpert PM, Morcos M, Wendt T, Chavakis T, Arnold B, Stern DM, Nawroth PP: Understanding RAGE, the receptor for advanced glycation end products. J Mol Med (Berl) 2005, 83:876-886.
Karachalias N, Babaei-Jadidi R, Rabbani N, Thornalley PJ: Increased protein damage in renal glomeruli, retina, nerve, plasma and urine and its prevention by thiamine and benfotiamine therapy in a rat model of diabetes. Diabetologia 2010, 53:1506-1516.
Karachalias N, Babaei-Jadidi R, Kupich C, Ahmed N, Thornalley PJ: High-dose thiamine therapy counters dyslipidemia and advanced glycation of plasma protein in streptozotocin-induced diabetic rats. Ann N Y Acad Sci 2005, 1043:777-783.
Stirban A, Negrean M, Stratmann B, Gawlowski T, Horstmann T, Götting C, Kleesiek K, Mueller-Roesel M, Koschinsky T, Uribarri J, Vlassara H, Tschoepe D: Benfotiamine prevents macro- and microvascular endothelial dysfunction and oxidative stress following a meal rich in advancedglycation end products in individuals with type 2 diabetes. Diabetes Care 2006, 29:2064-2071.
Kihm LP, Müller-Krebs S, Klein J, Ehrlich G, Mertes L, Gross ML, Adaikalakoteswari A, Thornalley PJ, Hammes HP, Nawroth PP, Zeier M, Schwenger V:Benfotiamine protects against peritoneal and kidney damage in peritoneal dialysis. J Am Soc Nephrol 2011, 22:914-926.
Polizzi FC, Andican G, Cetin E, Civelek S, Yumuk V, Burçak G: Increased DNA-Glycation in Type 2 Diabetic Patients: The Effect of Thiamine and Pyridoxine Therapy. Exp Clin Endocrinol Diabetes 2012, 120:329-934.