Novel plasma phospholipid biomarkers of autism: Mitochondrial dysfunction as a putative causative mechanism

Prostaglandins Leukotrienes and Essential Fatty Acids

Volumn 81, Issue 4, 2009, Pages 253-264

  Pastural, Élodie ^a   Ritchie, Shawn ^a   Lu, Yingshen ^a   Jin, Wei ^a   Kavianpour, Amir ^a   Khine Su Myat, Khine ^a   Heath, Doug ^a   Wood, Paul L ^a   Fisk, Maura ^b   Goodenowe, Dayan B ^a  

^a Phenomenome Discoveries Inc   (Canada)

^b Jonty Foundation   (United States)

Author keywords

Autism; Carnitine; Glutamate; Glutathione; Mitochondria; Plasmalogen; Very long chain fatty acid (VLCFA)

Indexed keywords

CYSTEINE; ETHANOLAMINE; FATTY ACID; GLUTAMIC ACID; GLUTATHIONE; LONG CHAIN FATTY ACID; METHIONINE; PHOSPHOLIPID; POLYUNSATURATED FATTY ACID; SATURATED FATTY ACID;

ARTICLE; ASTROCYTE; AUTISM; CHILD; CLINICAL ARTICLE; CONTROLLED STUDY; DISEASE COURSE; DISEASE MARKER; DISORDERS OF MITOCHONDRIAL FUNCTIONS; FATTY ACID OXIDATION; FEMALE; HUMAN; HUMAN CELL; LIPID METABOLISM; LIVER CELL; MALE; NERVE CELL; PATHOPHYSIOLOGY; PHOSPHOLIPID BLOOD LEVEL; PRIORITY JOURNAL; SIBLING;

ADOLESCENT; ASTROCYTES; AUTISTIC DISORDER; BIOLOGICAL MARKERS; CHILD; CHILD, PRESCHOOL; CYSTEINE; FATTY ACIDS; FEMALE; GLUTAMIC ACID; GLUTATHIONE; HEPATOCYTES; HUMANS; MALE; METHIONINE; MITOCHONDRIA; NEURONS; PHOSPHOLIPIDS; SIBLINGS;

EID: 70349507306     PISSN: 09523278     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.plefa.2009.06.003     Document Type: Article

References (88)

1. American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, fourth ed., 1994.
2. Yeargin-Allsopp M., Rice C., Karapurkar T., Doernberg N., Boyle C., and Murphy C. Prevalence of autism in a US metropolitan area. Jama 289 1 (2003) 49-55
3. DiCicco-Bloom E., Lord C., Zwaigenbaum L., Courchesne E., Dager S.R., Schmitz C., Schultz R.T., Crawley J., and Young L.J. The developmental neurobiology of autism spectrum disorder. J. Neurosci. 26 26 (2006) 6897-6906
4. Fombonne E. Epidemiological surveys of autism and other pervasive developmental disorders: an update. J. Autism. Dev. Disord. 33 4 (2003) 365-382
5. Vargas D.L., Nascimbene C., Krishnan C., Zimmerman A.W., and Pardo C.A. Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann. Neurol. 57 1 (2005) 67-81
6. Palmen S.J., Engeland H., Hof P.R., and Schmitz C. Neuropathological findings in autism. Brain 127 Part 12 (2004) 2572-2583
7. Courchesne E. Brainstem, cerebellar and limbic neuroanatomical abnormalities in autism. Curr. Opin. Neurobiol. 7 2 (1997) 269-278
8. Courchesne E., Redcay E., and Kennedy D.P. The autistic brain: birth through adulthood. Curr. Opin. Neurol. 17 4 (2004) 489-496
9. Herbert M.R., Ziegler D.A., Makris N., Filipek P.A., Kemper T.L., Normandin J.J., Sanders H.A., Kennedy D.N., and Caviness Jr. V.S. Localization of white matter volume increase in autism and developmental language disorder. Ann. Neurol. 55 4 (2004) 530-540
10. Yorbik O., Sayal A., Akay C., Akbiyik D.I., and Sohmen T. Investigation of antioxidant enzymes in children with autistic disorder. Prostaglandins Leukot. Essent. Fatty Acids 67 5 (2002) 341-343
11. Chauhan A., Chauhan V., Brown W.T., and Cohen I. Oxidative stress in autism: increased lipid peroxidation and reduced serum levels of ceruloplasmin and transferrin - the antioxidant proteins. Life Sci. 75 21 (2004) 2539-2549
12. Chauhan A., and Chauhan V. Oxidative stress in autism. Pathophysiology 13 3 (2006) 171-181
13. James S.J., Cutler P., Melnyk S., Jernigan S., Janak L., Gaylor D.W., and Neubrander J.A. Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. Am. J. Clin. Nutr. 80 6 (2004) 1611-1617
14. Sogut S., Zoroglu S.S., Ozyurt H., Yilmaz H.R., Ozugurlu F., Sivasli E., Yetkin O., Yanik M., Tutkun H., Savas H.A., Tarakcioglu M., and 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 331 1-2 (2003) 111-117
15. Zoroglu S.S., Armutcu F., Ozen S., Gurel A., Sivasli E., Yetkin O., and Meram I. Increased oxidative stress and altered activities of erythrocyte free radical scavenging enzymes in autism. Eur. Arch. Psychiatry Clin. Neurosci. 254 3 (2004) 143-147
16. Melke J., Goubran Botros H., Chaste P., Betancur C., Nygren G., Anckarsater H., Rastam M., Stahlberg O., Gillberg I.C., Delorme R., Chabane N., Mouren-Simeoni M.C., Fauchereau F., Durand C.M., Chevalier F., Drouot X., Collet C., Launay J.M., Leboyer M., Gillberg C., and Bourgeron T. Abnormal melatonin synthesis in autism spectrum disorders. Mol. Psychiatry 13 1 (2008) 90-98
17. Sliwinski S., Croonenberghs J., Christophe A., Deboutte D., and Maes M. Polyunsaturated fatty acids: do they have a role in the pathophysiology of autism?. Neuro. Endocrinol. Lett. 27 4 (2006) 465-471
18. Kern J.K., and Jones A.M. Evidence of toxicity, oxidative stress, and neuronal insult in autism. J. Toxicol. Environ. Health B Crit. Rev. 9 6 (2006) 485-499
19. Bauman M.L., and Kemper T.L. Neuroanatomic observations of the brain in autism: a review and future directions. Int. J. Dev. Neurosci. 23 2-3 (2005) 183-187
20. Aharoni A., Ric de Vos C.H., Verhoeven H.A., Maliepaard C.A., Kruppa G., Bino R., and Goodenowe D.B. Nontargeted metabolome analysis by use of fourier transform Ion cyclotron mass spectrometry. Omics 6 3 (2002) 217-234
21. Goodenowe D.B., Cook L.L., Liu J., Lu Y., Jayasinghe D.A., Ahiahonu P.W., Heath D., Yamazaki Y., Flax J., Krenitsky K.F., Sparks D.L., Lerner A., Friedland R.P., Kudo T., Kamino K., Morihara T., Takeda M., and Wood P.L. Peripheral ethanolamine plasmalogen deficiency: a logical causative factor in Alzheimer's disease and dementia. J. Lipid Res. 48 11 (2007) 2485-2498
22. Wood P.L., Khan M.A., and Moskal J.R. Neurochemical analysis of amino acids, polyamines and carboxylic acids: GC-MS quantitation of tBDMS derivatives using ammonia positive chemical ionization. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 831 (2006) 313-319
23. Geier D.A., and Geier M.R. A clinical and laboratory evaluation of methionine cycle-transsulfuration and androgen pathway markers in children with autistic disorders. Horm. Res. 66 4 (2006) 182-188
24. Filipek P.A., Juranek J., Nguyen M.T., Cummings C., and Gargus J.J. Relative carnitine deficiency in autism. J. Autism. Dev. Disord. 34 6 (2004) 615-623
25. Tirosh O., Sen C.K., Roy S., and Packer L. Cellular and mitochondrial changes in glutamate-induced HT4 neuronal cell death. Neuroscience 97 3 (2000) 531-541
26. Lumeng L., Bremer J., and Davis E.J. Suppression of the mitochondrial oxidation of (-)-palmitylcarnitine by the malate-aspartate and alpha-glycerophosphate shuttles. J. Biol. Chem. 251 2 (1976) 277-284
27. Vickers A.E., Bentley P., and Fisher R.L. Consequences of mitochondrial injury induced by pharmaceutical fatty acid oxidation inhibitors is characterized in human and rat liver slices. Toxicol. In Vitro 20 7 (2006) 1173-1182
28. Skorin C., Necochea C., Johow V., Soto U., Grau A.M., Bremer J., and Leighton F. Peroxisomal fatty acid oxidation and inhibitors of the mitochondrial carnitine palmitoyltransferase I in isolated rat hepatocytes. Biochem. J. 281 Part 2 (1992) 561-567
29. Hayashi H., and Hara M. 1-Alkenyl group of ethanolamine plasmalogen derives mainly from de novo-synthesized fatty alcohol within peroxisomes, but not extraperoxisomal fatty alcohol or fatty acid. J. Biochem. (Tokyo) 121 5 (1997) 978-983
30. Singh H., Beckman K., and Poulos A. Exclusive localization in peroxisomes of dihydroxyacetone phosphate acyltransferase and alkyl-dihydroxyacetone phosphate synthase in rat liver. J. Lipid Res. 34 3 (1993) 467-477
31. Voss A., Reinhart M., Sankarappa S., and Sprecher H. The metabolism of 7,10,13,16,19-docosapentaenoic acid to 4,7,10,13,16,19-docosahexaenoic acid in rat liver is independent of a 4-desaturase. J. Biol. Chem. 266 30 (1991) 19995-20000
32. Muhle R., Trentacoste S.V., and Rapin I. The genetics of autism. Pediatrics 113 5 (2004) e472-e486
33. Domercq M., Sanchez-Gomez M.V., Sherwin C., Etxebarria E., Fern R., and Matute C. System xc- and glutamate transporter inhibition mediates microglial toxicity to oligodendrocytes. J. Immunol. 178 10 (2007) 6549-6556
34. Matute C., Alberdi E., Domercq M., Sanchez-Gomez M.V., Perez-Samartin A., Rodriguez-Antiguedad A., and Perez-Cerda F. Excitotoxic damage to white matter. J. Anat. 210 6 (2007) 693-702
35. Bremer J., and Wojtczak A.B. Factors controlling the rate of fatty acid-oxidation in rat liver mitochondria. Biochim. Biophys. Acta 280 4 (1972) 515-530
36. Bartlett K., and Eaton S. Mitochondrial beta-oxidation. Eur. J. Biochem. 271 3 (2004) 462-469
37. Aoyama T., Peters J.M., Iritani N., Nakajima T., Furihata K., Hashimoto T., and Gonzalez F.J. Altered constitutive expression of fatty acid-metabolizing enzymes in mice lacking the peroxisome proliferator-activated receptor alpha (PPARalpha). J. Biol. Chem. 273 10 (1998) 5678-5684
38. Kondrup J., and Lazarow P.B. Flux of palmitate through the peroxisomal and mitochondrial beta-oxidation systems in isolated rat hepatocytes. Biochim. Biophys. Acta 835 1 (1985) 147-153
39. Hayashi H., and Takahata S. Role of peroxisomal fatty acyl-CoA beta-oxidation in phospholipid biosynthesis. Arch. Biochem. Biophys. 284 2 (1991) 326-331
40. Reszko A.E., Kasumov T., David F., Jobbins K.A., Thomas K.R., Hoppel C.L., Brunengraber H., and Des Rosiers C. Peroxisomal fatty acid oxidation is a substantial source of the acetyl moiety of malonyl-CoA in rat heart. J. Biol. Chem. 279 19 (2004) 19574-19579
41. Hayashi H., and Oohashi M. Incorporation of acetyl-CoA generated from peroxisomal beta-oxidation into ethanolamine plasmalogen of rat liver. Biochim. Biophys. Acta 1254 3 (1995) 319-325
42. Hayashi H., and Sato A. Fatty alcohol synthesis accompanied with chain elongation in liver peroxisomes. Biochim. Biophys. Acta 1346 1 (1997) 38-44
43. Sprecher H., Luthria D.L., Mohammed B.S., and Baykousheva S.P. Reevaluation of the pathways for the biosynthesis of polyunsaturated fatty acids. J. Lipid Res. 36 12 (1995) 2471-2477
44. Gaposchkin D.P., and Zoeller R.A. Plasmalogen status influences docosahexaenoic acid levels in a macrophage cell line. Insights using ether lipid-deficient variants. J. Lipid Res. 40 3 (1999) 495-503
45. Moser H.W., and Moser A.B. Very long-chain fatty acids in diagnosis, pathogenesis, and therapy of peroxisomal disorders. Lipids 31 Suppl. (1996) S141-S144
46. Kemp S., Valianpour F., Denis S., Ofman R., Sanders R.J., Mooyer P., Barth P.G., and Wanders R.J. Elongation of very long-chain fatty acids is enhanced in X-linked adrenoleukodystrophy. Mol. Genet. Metab. 84 2 (2005) 144-151
47. Hostetler H.A., Kier A.B., and Schroeder F. Very-long-chain and branched-chain fatty acyl-CoAs are high affinity ligands for the peroxisome proliferator-activated receptor alpha (PPARalpha). Biochemistry 45 24 (2006) 7669-7681
48. Wang Y., Botolin D., Xu J., Christian B., Mitchell E., Jayaprakasam B., Nair M.G., Peters J.M., Busik J.V., Olson L.K., and Jump D.B. Regulation of hepatic fatty acid elongase and desaturase expression in diabetes and obesity. J. Lipid Res. 47 9 (2006) 2028-2041
49. Wang Y., Botolin D., Christian B., Busik J., Xu J., and Jump D.B. Tissue-specific, nutritional, and developmental regulation of rat fatty acid elongases. J. Lipid Res. 46 4 (2005) 706-715
50. Pettegrew J.W., Levine J., and McClure R.J. Acetyl-l-carnitine physical-chemical, metabolic, and therapeutic properties: relevance for its mode of action in Alzheimer's disease and geriatric depression. Mol. Psychiatry 5 6 (2000) 616-632
51. Nalecz K.A., and Nalecz M.J. Carnitine - a known compound, a novel function in neural cells. Acta Neurobiol. Exp. (Wars) 56 2 (1996) 597-609
52. Bremer J. The role of carnitine in intracellular metabolism. J. Clin. Chem. Clin. Biochem. 28 5 (1990) 297-301
53. Bieber L.L. Carnitine. Annu. Rev. Biochem. 57 (1988) 261-283
54. Bourre J.M., and Piciotti M. Delta-6 desaturation of alpha-linolenic acid in brain and liver during development and aging in the mouse. Neurosci. Lett. 141 1 (1992) 65-68
55. Scott B.L., and Bazan N.G. Membrane docosahexaenoate is supplied to the developing brain and retina by the liver. Proc. Natl. Acad. Sci. USA 86 8 (1989) 2903-2907
56. Oliveira G., Diogo L., Grazina M., Garcia P., Ataide A., Marques C., Miguel T., Borges L., Vicente A.M., and Oliveira C.R. Mitochondrial dysfunction in autism spectrum disorders: a population-based study. Dev. Med. Child Neurol. 47 3 (2005) 185-189
57. Dumser M., Bauer J., Lassmann H., Berger J., and Forss-Petter S. Lack of adrenoleukodystrophy protein enhances oligodendrocyte disturbance and microglia activation in mice with combined Abcd1/Mag deficiency. Acta Neuropathol. 114 6 (2007) 573-586
58. Singh J., Khan M., and Singh I. Silencing of Abcd1 and Abcd2 genes sensitizes astrocytes for inflammation: implication for X-adrenoleukodystrophy. J. Lipid Res. (2008)
59. Ferrer I., Kapfhammer J.P., Hindelang C., Kemp S., Troffer-Charlier N., Broccoli V., Callyzot N., Mooyer P., Selhorst J., Vreken P., Wanders R.J., Mandel J.L., and Pujol A. Inactivation of the peroxisomal ABCD2 transporter in the mouse leads to late-onset ataxia involving mitochondria, Golgi and endoplasmic reticulum damage. Hum. Mol. Genet. 14 23 (2005) 3565-3577
60. Liang J., Takeuchi H., Doi Y., Kawanokuchi J., Sonobe Y., Jin S., Yawata I., Li H., Yasuoka S., Mizuno T., and Suzumura A. Excitatory amino acid transporter expression by astrocytes is neuroprotective against microglial excitotoxicity. Brain Res. 1210 (2008) 11-19
61. Piani D., and Fontana A. Involvement of the cystine transport system xc- in the macrophage-induced glutamate-dependent cytotoxicity to neurons. J. Immunol. 152 7 (1994) 3578-3585
62. Zhao W., Xie W., Le W., Beers D.R., He Y., Henkel J.S., Simpson E.P., Yen A.A., Xiao Q., and Appel S.H. Activated microglia initiate motor neuron injury by a nitric oxide and glutamate-mediated mechanism. J. Neuropathol. Exp. Neurol. 63 9 (2004) 964-977
63. Brown D.R. Neurons depend on astrocytes in a coculture system for protection from glutamate toxicity. Mol. Cell Neurosci. 13 5 (1999) 379-389
64. Rosenberg P.A., and Aizenman E. Hundred-fold increase in neuronal vulnerability to glutamate toxicity in astrocyte-poor cultures of rat cerebral cortex. Neurosci. Lett. 103 2 (1989) 162-168
65. Fombonne E. Epidemiology of autistic disorder and other pervasive developmental disorders. J. Clin. Psychiatry 66 Suppl. 10 (2005) 3-8
66. Fombonne E. The epidemiology of autism: a review. Psychol. Med. 29 4 (1999) 769-786
67. Ritvo E.R., Freeman B.J., Pingree C., Mason-Brothers A., Jorde L., Jenson W.R., McMahon W.M., Petersen P.B., Mo A., and Ritvo A. The UCLA-University of Utah epidemiologic survey of autism: prevalence. Am. J. Psychiatry 146 2 (1989) 194-199
68. Horlick M.B., Rosenbaum M., Nicolson M., Levine L.S., Fedun B., Wang J., Pierson Jr. R.N., and Leibel R.L. Effect of puberty on the relationship between circulating leptin and body composition. J. Clin. Endocrinol. Metab. 85 7 (2000) 2509-2518
69. Klein K.O., Baron J., Colli M.J., McDonnell D.P., and Cutler Jr. G.B. Estrogen levels in childhood determined by an ultrasensitive recombinant cell bioassay. J. Clin. Invest. 94 6 (1994) 2475-2480
70. Goodman Y., Bruce A.J., Cheng B., and Mattson M.P. Estrogens attenuate and corticosterone exacerbates excitotoxicity, oxidative injury, and amyloid beta-peptide toxicity in hippocampal neurons. J. Neurochem. 66 5 (1996) 1836-1844
71. Harms C., Lautenschlager M., Bergk A., Katchanov J., Freyer D., Kapinya K., Herwig U., Megow D., Dirnagl U., Weber J.R., and Hortnagl H. Differential mechanisms of neuroprotection by 17 beta-estradiol in apoptotic versus necrotic neurodegeneration. J. Neurosci. 21 8 (2001) 2600-2609
72. Hilton G.D., Ndubuizu A.N., and McCarthy M.M. Neuroprotective effects of estradiol in newborn female rat hippocampus. Brain Res. Dev. Brain Res. 150 2 (2004) 191-198
73. McClean J., and Nunez J.L. 17alpha-Estradiol is neuroprotective in male and female rats in a model of early brain injury. Exp. Neurol. 210 1 (2008) 41-50
74. Mendelowitsch A., Ritz M.F., Ros J., Langemann H., and Gratzl O. 17beta-Estradiol reduces cortical lesion size in the glutamate excitotoxicity model by enhancing extracellular lactate: a new neuroprotective pathway. Brain Res. 901 1-2 (2001) 230-236
75. Nilsen J., and Diaz Brinton R. Mechanism of estrogen-mediated neuroprotection: regulation of mitochondrial calcium and Bcl-2 expression. Proc. Natl. Acad. Sci. USA 100 5 (2003) 2842-2847
76. Singer C.A., Rogers K.L., Strickland T.M., and Dorsa D.M. Estrogen protects primary cortical neurons from glutamate toxicity. Neurosci. Lett. 212 1 (1996) 13-16
77. Vavaiya K.V., and Briski K.P. Effects of caudal hindbrain lactate infusion on insulin-induced hypoglycemia and neuronal substrate transporter glucokinase and sulfonylurea receptor-1 gene expression in the ovariectomized female rat dorsal vagal complex: impact of estradiol. J. Neurosci. Res. 86 3 (2008) 694-701
78. Zhang Y., Lu X., and Bhavnani B.R. Equine estrogens differentially inhibit DNA fragmentation induced by glutamate in neuronal cells by modulation of regulatory proteins involved in programmed cell death. BMC Neurosci. 4 (2003) 32
79. Djouadi F., Weinheimer C.J., Saffitz J.E., Pitchford C., Bastin J., Gonzalez F.J., and Kelly D.P. A gender-related defect in lipid metabolism and glucose homeostasis in peroxisome proliferator-activated receptor alpha-deficient mice. J. Clin. Invest. 102 6 (1998) 1083-1091
80. Schneider G.H., Baethmann A., and Kempski O. Mechanisms of glial swelling induced by glutamate. Can. J. Physiol. Pharmacol. 70 Suppl. (1992) S334-S343
81. Geier D.A., Kern J.K., Garver C.R., Adams J.B., Audhya T., and Geier M.R.A. Prospective study of transsulfuration biomarkers in autistic disorders. Neurochem. Res. (2008)
82. Chen C.J., Liao S.L., and Kuo J.S. Gliotoxic action of glutamate on cultured astrocytes. J. Neurochem. 75 4 (2000) 1557-1565
83. Ming X., Stein T.P., Brimacombe M., Johnson W.G., Lambert G.H., and Wagner G.C. Increased excretion of a lipid peroxidation biomarker in autism. Prostaglandins Leukot. Essent. Fatty Acids 379 5 (2005) 379-384
84. Wood P.L., Khan M.A., Kulow S.R., Mahmood S.A., and Moskal J.R. Neurotoxicity of reactive aldehydes: the concept of "aldehyde load" as demonstrated by neuroprotection with hydroxylamines. Brain Res. 1095 1 (2006) 190-199
85. Dringen R. Oxidative and antioxidative potential of brain microglial cells. Antioxidants Redox Signaling*** 7 9-10 (2005) 1223-1233
86. Eichler F.S., Ren J.Q., Cossoy M., Rietsch A.M., Nagpal S., Moser A.B., Frosch M.P., and Ransohoff R.M. Is microglial apoptosis an early pathogenic change in cerebral X-linked adrenoleukodystrophy?. Ann. Neurol. 63 6 (2008) 729-742
87. Brites P., Mooyer P.A.W., Mrabet L., Waterham H.R., and Wanders R.J.A. Plasmalogens participate in very-long-chain fatty acid-induced pathology. Brain 132 (2009) 482-492
88. Blaylock R.L. A possible central mechanism in autism spectrum disorders, Part I. Altern. Ther. Health Med. 14 6 (2008) 46-53