Folate and neurological disease: Basic mechanisms

Folate in Health and Disease, Second Edition

Volumn , Issue , 2009, Pages 355-380

  Bottiglieri, Teodoro ^a   Reynolds, Edward ^b  

^a BAYLOR UNIVERSITY MEDICAL CENTER   (United States)

^b KING'S COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 84855752350     PISSN: None     EISSN: None     Source Type: Book    
DOI: None     Document Type: Chapter

References (160)

1. Reynolds EH. Folic acid, vitamin B12 and the nervous system: Historical aspects. In Botez MI, Reynolds EH, eds., Folic Acid in Neurology, Psychiatry and Internal Medicine. New York: Raven Press, 1979:1-5.
2. Bottiglieri T, Crellin R, Reynolds EH. Folates and neuropsychiatry. In Bailey L, ed., Folate in Health and Disease, 1st ed. New York: Marcel Dekker, 1995:435-62.
3. Reynolds E. Vitamin B12, folic acid, and the nervous system. Lancet Neurol 2006; 5:949-60.
4. Goyette P, Frosst P, Rosenblatt DS, Rozen R. Seven novel mutations in the methyl-enetetrahydro folate reductase gene and genotype/phenotype correlations in severe methylenetetrahydrofolate reductase deficiency. Am J Hum Genet 1995; 56:1052-59.
5. Rosenblatt DS, Fenton WA. Inherited disorders of folate and cobalamin transport and metabolism. In Scriver CS, Beaudet AL, Sly WS, Calle D, eds., The Metabolic Basis of Inherited Disease, 8th ed. New York: McGraw-Hill, 2001:3897-933.
6. Whitehead VM. Acquired and inherited disorders of cobalamin and folate in children. Br J Haematol 2006; 134:125-36.
7. Iskandar BJ, Nelson A, Resnick D, Skene JH, Gao P, Johnson C, Cook TD, Hariharan N. Folic acid supplementation enhances repair of the adult central nervous system. Ann Neurol 2004; 56:221-27.
8. MRC Vitamin Study Research Group. Prevention of neural tube defects: Results of the Medical Research Council Vitamin Study. Lancet 1991; 338:131-37.
9. Shorvon SD, Carney MW, Chanarin I, Reynolds EH. The neuropsychiatry of megaloblastic anaemia. BMJ 1980; 281:1036-38.
10. Reynolds EH. Neurological aspects of folate and vitamin B12 metabolism. Clin Haematol 1976; 5:661-96.
11. Reynolds EH. Folic acid, ageing, depression, and dementia. BMJ 2002; 324:1512-15.
12. Morris MS. Folate, homocysteine, and neurological function. Nutr Clin Care 2002; 5:124-32.
13. D’Anci KE, Rosenberg IH. Folate and brain function in the elderly. Curr Opin Clin Nutr Metab Care 2004; 7:659-64.
14. Matherly LH, Godman ID. Membrane transport of folates. Vitam Horm 2003; 66:403-56.
15. Qiu A, Jansen M, Sakaris A, Min SH, Chattopadhyay S, Tsai E, Sandoval C, Zhao R, Akabas MH, Goldman ID. Identification of an intestinal folate transporter and the molecular basis for hereditary folate malabsorption. Cell 2006; 127:917-28.
16. Balamurugan K, Said HM. Role of reduced folate carrier in intestinal folate uptake. Am J Physiol Cell Physiol 2006; 291:C189-93.
17. Kneuer C, Honscha KU, Honscha W. Rat reduced-folate carrier-1 is localized baso-laterally in MDCK kidney epithelial cells and contributes to the secretory transport of methotrexate and fluoresceinated methotrexate. Cell Tissue Res 2005; 320:517-24.
18. Sweiry JH, Yudilevich DL. Transport of folates at maternal and fetal sides of the placenta: Lack of inhibition by methotrexate. Biochim Biophys Acta 1985; 19;821:497-501.
19. Spector R, Johanson C. Micronutrient and urate transport in choroid plexus and kidney: Implications for drug therapy. Pharm Res 2006; 23:2515-24.
20. Antony AC. The biological chemistry of folate receptors. Blood 1992; 79:2807-20.
21. Westerhof GR, Schornagel JH, Kathmann I, Jackman AL, Rosowsky A, Forsch RA, Hynes JB, Boyle FT, Peters GJ, Pinedo HM. Carrier- and receptor-mediated transport of folate antagonists targeting folate-dependent enzymes: Correlates of molecular-structure and biological activity. Mol Pharmacol 1995; 48:459-71.
22. Piedrahita JA, Oetama B, Bennett GD, van Waes J, Kamen BA, Richardson J, Lacey SW, Anderson RG, Finnell RH. Mice lacking the folic acid-binding protein Folbp1 are defective in early embryonic development. Nat Genet 1999; 23:228-32.
23. Wollack JB, Makori B, Ahlawat S, Koneru R, Picinich SC, Smith A, Goldman ID, et al. Characterization of folate uptake by choroid plexus epithelial cells in a rat primary culture model. JNeurochem 2008; 104:1494-503.
24. Kamen BA, Smith AK. A review of folate receptor alpha cycling and 5-methyltetra-hydrofolate accumulation with an emphasis on cell models in vitro. Adv Drug Deliv Rev2004; 56:1085-97.
25. Tran T, Shatnawi A, Zheng X, Kelley KM, Ratnam M. Enhancement of folate receptor alpha expression in tumor cells through the glucocorticoid receptor: A promising means to improved tumor detection and targeting. Cancer Res 2005; 65:4431-41.
26. Rothberg KG, Ying YS, Kamen BA, Anderson RG. Cholesterol controls the clustering of the glycophospholipid-anchored membrane receptor for 5-methyltetrahydrofolate. J Cell Biol 1990; 111:2931-38.
27. Müller G, Dearey EA, Pünter J. The sulphonylurea drug, glimepiride, stimulates release of glycosylphosphatidylinositol-anchored plasma-membrane proteins from 3T3 adipocytes. Biochem J 1993; 289:509-21.
28. Ramaekers VT, Häusler M, Opladen T, Heimann G, Blau N. Psychomotor retardation, spastic paraplegia, cerebellar ataxia and dyskinesia associated with low 5-methyltet-rahydrofolate in cerebrospinal fluid: A novel neurometabolic condition responding to folinic acid substitution. Neuropediatrics 2002; 33:301-08.
29. Ramaekers VT, Blau N. Cerebral folate deficiency. Dev Med Child Neurol 2004; 46:843-51.
30. Rothenberg SP, da Costa MP, Sequeira JM, Cracco J, Roberts JL, Weedon J, Quadros EV. Autoantibodies against folate receptors in women with a pregnancy complicated by a neural-tube defect. N Engl J Med 2004; 350:134-42.
31. Ramaekers VT, Rothenberg SP, Sequeira JM, Opladen T, Blau N, Quadros EV, Selhub J. Autoantibodies to folate receptors in the cerebral folate deficiency syndrome. N Engl J Med 2005; 352:1985-91.
32. Ramaekers VT, Hansen SI, Holm J, Opladen T, Senderek J, Häusler M, Heimann G, Fowler B, Maiwald R, Blau N. Reduced folate transport to the CNS in female Rett patients. Neurology 2003; 61:506-15.
33. Moretti P, Sahoo T, Hyland K, Bottiglieri T, Peters S, del Gaudio D, Roa B, et al.Cerebral folate deficiency with developmental delay, autism, and response to folinic acid. Neurology 2005; 64:1088-90.
34. Spector R, Lorenzo AV. Folate transport in the central nervous system. Am J Physiol1975; 229:777-82.
35. Reynolds EH, Gallagher BB, Mattson RH, Bowers M, Johnson AL. Relationship between serum and cerebrospinal fluid folate. Nature 1972; 240:155-57.
36. Surtees R, Hyland K. Cerebrospinal fluid concentrations of S-adenosylmethionine, methionine, and 5-methyltetrahydrofolate in a reference population: Cerebrospinal fluid S-adenosylmethionine declines with age in humans. Biochem Med Metab Biol 1990; 44:192-99.
37. Ormazabal A, Garcia-Cazorla A, Pérez-Duenas B, Gonzalez V, Fernandez-Alvarez E, Pineda M, Campistol J, Artuch R. Determination of 5-methyltetrahydrofolate in cerebrospinal fluid of paediatric patients: Reference values for a paediatric population. Clin Chim Acta 2006; 371:159-62.
38. Verbeek MM, Blom AM, Wevers RA, Lagerwerf AJ, van de Geer J, Willemsen MA. Technical and biochemical factors affecting cerebrospinal fluid 5-MTHF, biopterin and neopterin concentrations. Mol Genet Metab 2008; 95:127-32.
39. Bottiglieri T, Reynolds EH, Laundy M. Folate in CSF and age. J Neurol Neurosurg Psychiatry 2000; 69:562.
40. Serot JM, Barbé F, Arning E, Bottiglieri T, Franck P, Montagne P, Nicolas JP. Homocysteine and methylmalonic acid concentrations in cerebrospinal fluid: Relation with age and Alzheimer’s disease. J Neurol Neurosurg Psychiatry 2005; 76:1585-87.
41. Obeid R, Kostopoulos P, Knapp JP, Kasoha M, Becker G, Fassbender K, Herrmann W. Biomarkers of folate and vitamin B12 are related in blood and cerebrospinal fluid. Clin Chem 2007; 53:326-33.
42. Hagnelius NO, Wahlund LO, Nilsson TK. CSF/serum folate gradient: Physiology and determinants with special reference to dementia. Dement Geriatr Cogn Disord 2008; 25:516-23.
43. Neymeyer V, Tephly TR, Miller MW. Folate and 10-formyltetrahydrofolate dehydrogenase (FDH) expression in the central nervous system of the mature rat. Brain Res 1997; 766:195-204.
44. Sunden SL, Renduchintala MS, Park EI, Miklasz SD, Garrow TA. Betaine-homocysteine methyltransferase expression in porcine and human tissues and chromosomal localization of the human gene. Arch Biochem Biophys 1997; 345:171-74.
45. Stabler SP, Marcell PD, Podell ER, Allen RH, Savage DG, Lindenbaum J. Elevation of total homocysteine in the serum of patients with cobalamin or folate deficiency detected by capillary gas chromatography-mass spectrometry. J Clin Invest 1988; 81:466-74.
46. Lindenbaum J, Healton EB, Savage DG, Brust JC, Garrett TJ, Podell ER, Marcell PD, Stabler SP, Allen RH. Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis. N Engl J Med 1988; 318:1720-28.
47. Chanarin I, Deacon R, Lumb M, Perry J. Cobalamin and folate: Recent developments. J Clin Pathol 1992; 45:277-83.
48. Strauss KA, Morton DH, Puffenberger EG, Hendrickson C, Robinson DL, Wagner C, Stabler SP, et al. Prevention of brain disease from severe 5,10-methylenetetrahydro-folate reductase deficiency. Mol Genet Metab 2007; 91:165-75.
49. Bottiglieri T. Isocratic high performance liquid chromatographic analysis of S-adenosylmethionine and S-adenosylhomocysteine in animal tissues: The effect of exposure to nitrous oxide. Biomed Chromatogr 1990; 4:239-41.
50. Surtees R, Leonard J, Austin S. Association of demyelination with deficiency of cerebrospinal-fluid S-adenosylmethionine in inborn errors of methyl-transfer pathway. Lancet1991; 338:1550-54.
51. Devlin AM, Arning E, Bottiglieri T, Faraci FM, Rozen R, Lentz SR. Effect of Mthfr genotype on diet-induced hyperhomocysteinemia and vascular function in mice. Blood2004;103:2624-29.
52. Dayal S, Devlin AM, McCaw RB, Liu ML, Arning E, Bottiglieri T, Shane B, Faraci FM, Lentz SR. Cerebral vascular dysfunction in methionine synthase-deficient mice. Circulation 2005; 112:737-44.
53. Cantoni GL. The role of S-adenosylhomocysteine in the biological utilization of S-adenosylmethionine. Prog Clin Biol Res 1985; 198:47-65.
54. Chiang PK. Biological effects of inhibitors of S-adenosylhomocysteine hydrolase. Pharmacol Ther 1998; 77:115-34.
55. Lever EG, Elwes RD, Williams A, Reynolds EH. Subacute combined degeneration of the cord due to folate deficiency: Response to methyl folate treatment. J Neurol Neurosurg Psychiatry 1986; 49:1203-07.
56. Reynolds EH, Bottiglieri T, Laundy M, Stern J, Payan J, Linnell J, Faludy J. Subacute combined degeneration with high serum vitamin B12 level and abnormal vitamin B12 binding protein. New cause of an old syndrome. Arch Neurol 1993; 50:739-42.
57. Bottiglieri T. Folate, vitamin B12, and neuropsychiatric disorders. Nutr Rev 1996; 54:382-90.
58. Hyland K, Smith I, Bottiglieri T, Perry J, Wendel U, Clayton PT, Leonard JV. Demyelination and decreased S-adenosylmethionine in 5,10-methylenetetrahydrofolate reductase deficiency. Neurology 1988; 38:459-62.
59. Kishi T, Tanaka Y, Ueda K. Evidence for hypomethylation in two children with acute lymphoblastic leukemia and leukoencephalopathy. Cancer 2000; 89:925-31.
60. Bottiglieri T, Godfrey P, Flynn T, Carney MW, Toone BK, Reynolds EH. Cerebrospinal fluid S-adenosylmethionine in depression and dementia: Effects of treatment with parenteral and oral S-adenosylmethionine. J Neurol Neurosurg Psychiatry 1990; 53:1096-98.
61. Bottiglieri T, Laundy M, Crellin R, Toone BK, Carney MW, Reynolds EH. Homocysteine, folate, methylation, and monoamine metabolism in depression. J Neurol Neurosurg Psychiatry 2000; 69:228-32.
62. Mulder C, Schoonenboom NS, Jansen EE, Verhoeven NM, van Kamp GJ, Jakobs C, Scheltens P. The transmethylation cycle in the brain of Alzheimer patients. Neurosci Lett2005; 386:69-71.
63. Scott JM, Dinn JJ, Wilson P, Weir DG. Pathogenesis of subacute combined degeneration: A result of methyl group deficiency. Lancet 1981; 2:334-37.
64. Metz J. Cobalamin deficiency and the pathogenesis of nervous system disease. Annu Rev Nutr 1992; 12:59-79.
65. Weir DG, Molloy AM, Keating JN, Young PB, Kennedy S, Kennedy DG, Scott JM. Correlation of the ratio of S-adenosyl-L-methionine to S-adenosyl-L-homocysteine in the brain and cerebrospinal fluid of the pig: Implications for the determination of this methylation ratio in human brain. Clin Sci (Lond) 1992; 82:93-97.
66. McKeever M, Molloy A, Weir DG, Young PB, Kennedy DG, Kennedy S, Scott JM. An abnormal methylation ratio induces hypomethylation in vitro in the brain of pig and man, but not in rat. Clin Sci (Lond) 1995; 88:73-79.
67. Small DH, Carnegie PR. In vivo methylation of an arginine in chicken myelin basic protein. J Neurochem 1982; 38:184-90.
68. Kim S, Lim IK, Park GH, Paik WK. Biological methylation of myelin basic protein: Enzymology and biological significance. Int J Biochem Cell Biol 1997; 29:743-51.
69. Janssens V, Longin S, Goris J. PP2A holoenzyme assembly: In cauda venenum (the sting is in the tail). Trends Biochem Sci 2008; 33:113-21.
70. Sontag E, Nunbhakdi-Craig V, Lee G, Bloom GS, Mumby MC. Regulation of the phosphorylation state and microtubule-binding activity of Tau by protein phosphatase 2A. Neuron 1996; 17:1201-07.
71. Sontag E, Nunbhakdi-Craig V, Lee G, Brandt R, Kamibayashi C, Kuret J, White CL 3rd, Mumby MC, Bloom GS. Molecular interactions among protein phosphatase 2A, tau, and microtubules. Implications for the regulation of tau phosphorylation and the development of tauopathies. J Biol Chem 1999; 274:25490-98.
72. Xu Y, Chen Y, Zhang P, Jeffrey PD, Shi Y. Structure of a protein phosphatase 2A holoenzyme: Insights into B55-mediated Tau dephosphorylation. Mol Cell 2008; 31:873-85.
73. De Baere I, Derua R, Janssens V, Van Hoof C, Waelkens E, Merlevede W, Goris J. Purification of porcine brain protein phosphatase 2A leucine carboxyl methyltransferase and cloning of the human homologue. Biochemistry 1999; 38:16539-47.
74. Leulliot N, Quevillon-Cheruel S, Sorel I, de La Sierra-Gallay IL, Collinet B, Graille M, Blondeau K, et al. Structure of protein phosphatase methyltransferase 1 (PPM1), a leucine carboxyl methyltransferase involved in the regulation of protein phosphatase 2A activity. J Biol Chem 2004; 279:8351-58.
75. Ogris E, Du X, Nelson KC, Mak EK, Yu XX, Lane WS, Pallas DC. A protein phosphatase methylesterase (PME-1) is one of several novel proteins stably associating with two inactive mutants of protein phosphatase 2A. J Biol Chem 1999; 274:14382-91.
76. Sontag E, Nunbhakdi-Craig V, Sontag JM, Diaz-Arrastia R, Ogris E, Dayal S, Lentz SR, Arning E, Bottiglieri T. Protein phosphatase 2A methyltransferase links homocysteine metabolism with tau and amyloid precursor protein regulation. J Neurosci2007; 27:2751-59.
77. Sontag JM, Nunbhakdi-Craig V, Montgomery L, Arning E, Bottiglieri T, Sontag E. Folate deficiency induces in vitro and mouse brain region-specific downregulation of leucine carboxyl methyltransferase-1 and protein phosphatase 2A B(alpha) subunit expression that correlate with enhanced tau phosphorylation. J Neurosci 2008; 28:11477-87.
78. Sontag E, Hladik C, Montgomery L, Luangpirom A, Mudrak I, Ogris E, White CL 3rd. Downregulation of protein phosphatase 2A carboxyl methylation and methyltransferase may contribute to Alzheimer disease pathogenesis. J Neuropathol Exp Neurol 2004; 63:1080-91.
79. Yoon SY, Choi HI, Choi JE, Sul CA, Choi JM, Kim DH. Methotrexate decreases PP2A methylation and increases tau phosphorylation in neuron. Biochem Biophys Res Commun2007; 363:811-16.
80. Lee MS, Kao SC, Lemere CA, Xia W, Tseng HC, Zhou Y, Neve R, Ahlijanian MK, Tsai LH. APP processing is regulated by cytoplasmic phosphorylation. J Cell Biol 2003; 163:83-95.
81. Chang KA, Kim HS, Ha TY, Ha JW, Shin KY, Jeong YH, Lee JP, et al. Phosphorylation of amyloid precursor protein (APP) at Thr668 regulates the nuclear translocation of the APP intracellular domain and induces neurodegeneration. Mol Cell Biol 2006; 26:4327-38.
82. Jacob RA. Folate, DNA methylation, and gene expression: Factors of nature and nurture. Am J Clin Nutr 2000; 72:903-04.
83. Ulrey CL, Liu L, Andrews LG, Tollefsbol TO. The impact of metabolism on DNA methylation. Hum Mol Genet 2005; 14:139-47.
84. Watt F, Molloy PL. Cytosine methylation prevents binding to DNA of a HeLa cell transcription factor required for optimal expression of the adenovirus major late promoter. Genes Dev 1988; 2:1136-43.
85. Robertson KD, Wolffe AP. DNA methylation in health and disease. Nat Rev Genet 2000; 1:11-19.
86. Ramaekers VT, Sequeira JM, Artuch R, Blau N, Temudo T, Ormazabal A, Pineda M, et al. Folate receptor autoantibodies and spinal fluid 5-methyltetrahydrofolate deficiency in Rett syndrome. Neuropediatrics 2007; 38:179-83.
87. Neul JL, Maricich SM, Islam M, Barrish J, Smith EO, Bottiglieri T, Hyland K, Humphreys P, Percy A, Glaze D. Spinal fluid 5-methyltetrahydrofolate levels are normal in Rett syndrome. Neurology 2005; 64:2151-52.
88. Temudo T, Rios M, Prior C, Carrilho I, Santos M, Maciel P, Sequeiros J, et al. Evaluation of CSF neurotransmitters and folate in 25 patients with Rett disorder and effects of treatment. Brain Dev 2009; 31:46-51.
89. Martinowich K, Hattori D, Wu H, Fouse S, He F, Hu Y, Fan G, Sun YE. DNA methyla-tion-related chromatin remodeling in activity-dependent BDNF gene regulation. Science2003; 302:890-93.
90. Chen WG, Chang Q, Lin Y, Meissner A, West AE, Griffith EC, Jaenisch R, Greenberg ME. Derepression of BDNF transcription involves calcium-dependent phosphorylation of MeCP2. Science 2003; 302:885-89.
91. Cunha C, Angelucci A, D’Antoni A, Dobrossy MD, Dunnett SB, Berardi N, Brambilla R. Brain-derived neurotrophic factor (BDNF) overexpression in the forebrain results in learning and memory impairments. Neurobiol Dis 2009; 33:358-68.
92. Liu L, van Groen T, Kadish I, Tollefsbol TO. DNA methylation impacts on learning and memory in aging. Neurobiol Aging 2009; 30:549-60.
93. Abdolmaleky HM, Cheng KH, Faraone SV, Wilcox M, Glatt SJ, Gao F, Smith CL, et al.Hypomethylation of MB-COMT promoter is a major risk factor for schizophrenia and bipolar disorder. Hum Mol Genet 2006; 15:3132-45.
94. Roffman JL, Gollub RL, Calhoun VD, Wassink TH, Weiss AP, Ho BC, White T, et al.MTHFR 677C --> T genotype disrupts prefrontal function in schizophrenia through an interaction with COMT 158Val --> Met. Proc Natl Acad Sci USA 2008; 105:17573-78.
95. Lippa CF. Familial Alzheimer’s disease: Genetic influences on the disease process. Review. Int J Mol Med 1999; 4:529-36.
96. Tohgi H, Utsugisawa K, Nagane Y, Yoshimura M, Genda Y, Ukitsu M. Reduction with age in methylcytosine in the promoter region -224 approximately -101 of the amyloid precursor protein gene in autopsy human cortex. Brain Res Mol Brain Res 1999; 70:288-92.
97. West RL, Lee JM, Maroun LE. Hypomethylation of the amyloid precursor protein gene in the brain of an Alzheimer’s disease patient. J Mol Neurosci 1995; 6:141-46.
98. Fuso A, Seminara L, Cavallaro RA, D’Anselmi F, Scarpa S. S-adenosylmethionine/homo-cysteine cycle alterations modify DNA methylation status with consequent deregulation of PS1 and BACE and beta-amyloid production. Mol Cell Neurosci 2005; 28:195-204.
99. Scarpa S, Fuso A, D’Anselmi F, Cavallaro RA. Presenilin 1 gene silencing by S-adenosylmethionine: A treatment for Alzheimer disease? FEBS Lett 2003; 541: 145-48.
100. Fuso A, Nicolia V, Cavallaro RA, Ricceri L, D’Anselmi F, Coluccia P, Calamandrei G, Scarpa S. B-vitamin deprivation induces hyperhomocysteinemia and brain S-adenosylhomocysteine, depletes brain S-adenosylmethionine, and enhances PS1 and BACE expression and amyloid-beta deposition in mice. Mol Cell Neurosci 2008; 37:731-46.
101. Crews FT. Effects of membrane fluidity on secretion and receptor stimulation. Psychopharmacol Bull 1982; 18:135-43.
102. Hirata F, Strittmatter WJ, Axelrod J. beta-Adrenergic receptor agonists increase phospholipid methylation, membrane fluidity, and beta-adrenergic receptor-adenylate cyclase coupling. Proc Natl Acad Sci USA 1979; 76:368-72.
103. Muccioli G, Scordamaglia A, Bertacco S, Di Carlo R. Effect of S-adenosyl-L-methionine on brain muscarinic receptors of aged rats. Eur J Pharmacol 1992; 227:293-99.
104. Di Perri B, Calderini G, Battistella A, Raciti R, Toffano G. Phospholipid methylation increases [3H]diazepam and [3H]GABA binding in membrane preparations of rat cerebellum. J Neurochem 1983; 41:302-08.
105. Blusztajn JK, Liscovitch M, Richardson UI. Synthesis of acetylcholine from choline derived from phosphatidylcholine in a human neuronal cell line. Proc Natl Acad Sci USA 1987; 84:5474-77.
106. Akesson B, Fehling C, Jägerstad M, Stenram U. Effect of experimental folate deficiency on lipid metabolism in liver and brain. Br J Nutr 1982; 47:505-20.
107. Troen AM, Chao WH, Crivello NA, D’Anci KE, Shukitt-Hale B, Smith DE, Selhub J, Rosenberg IH. Cognitive impairment in folate-deficient rats corresponds to depleted brain phosphatidylcholine and is prevented by dietary methionine without lowering plasma homocysteine. J Nutr 2008; 138:2502-09.
108. Pettegrew JW, Kopp SJ, Minshew NJ, Glonek T, Feliksik JM, Tow JP, Cohen MM. 31P nuclear magnetic resonance studies of phosphoglyceride metabolism in developing and degenerating brain: Preliminary observations. JNeuropathol Exp Neurol 1987; 46:419-30.
109. Forlenza OV, Wacker P, Nunes PV, Yacubian J, Castro CC, Otaduy MC, Gattaz WF. Reduced phospholipid breakdown in Alzheimer’s brains: A 31P spectroscopy study. Psychopharmacology (Berl) 2005; 180:359-65.
110. Botez MI, Young SN, Bachevalier J, Gauthier S. Folate deficiency and decreased brain 5-hydroxytryptamine synthesis in man and rat. Nature 1979; 278:182-83.
111. Botez MI, Young SN. Effects of anticonvulsant treatment and low levels of folate and thiamine on amine metabolites in cerebrospinal fluid. Brain 1991; 114:333-48.
112. Bottiglieri T, Hyland K, Laundy M, Godfrey P, Carney MW, Toone BK, Reynolds EH. Folate deficiency, biopterin and monoamine metabolism in depression. Psychol Med1992; 22:871-76.
113. Gospe SM Jr, Gietzen DW, Summers PJ, Lunetta JM, Miller JW, Selhub J, Ellis WG, Clifford AJ. Behavioral and neurochemical changes in folate-deficient mice. Physiol Behav 1995; 58:935-41.
114. Kaufman S. Regulatory properties of pterin-dependent hydroxylases: Variations on a theme. In Usdin E, Weiner N, Youdim MBH, eds., Function and Regulation of Monoamine Enzymes. New York: Macmillian, 1981:165-73.
115. Topal G, Brunet A, Millanvoye E, Boucher JL, Rendu F, Devynck MA, David-Dufilho M. Homocysteine induces oxidative stress by uncoupling of NO synthase activity through reduction of tetrahydrobiopterin. Free Radic Biol Med 2004; 36:1532-41.
116. Hamon CBG, Blair JA, Barford PA. The effect of methyltetrahydrofolate on tetrahydrobiopterin metabolism. J Mental Def Res 1986; 30:170-83.
117. Kaufman S. Some metabolic relationships between biopterin and folate: Implications for the methyl trap hypothesis. Neurochem Res 1991; 16:1031-36.
118. Sawabe K, Wakasuqi K, Haseqwa H. Tetrahydrobiopterin uptake in supplemental administration: Elevation of tissue tetrahydrobiopterin in mice following uptake of the exogenously oxidized product 7,8-dihydrobiopterin and subsequent reduction by an anti-folate-sensitive process. J Pharmacol Sci 2004; 96:124-33.
119. Gilbody S, Lewis S, Lightfoot T. Methylenetetrahydrofolate reductase (MTHFR) genetic polymorphisms and psychiatric disorders: A HuGE review. Am J Epidemiol2007; 165:1-13.
120. Kelly CB, McDonnell AP, Johnston TG, Mulholland C, Cooper SJ, McMaster D, Evans A, Whitehead AS. The MTHFR C677T polymorphism is associated with depressive episodes in patients from Northern Ireland. J Psychopharmacol 2004; 18:567-71.
121. Wesson VA, Levitt AJ, Joffe RT. Change in folate status with antidepressant treatment. Psychiatry Res 1994; 53:313-22.
122. Fava M, Borus JS, Alpert JE, Nierenberg AA, Rosenbaum JF, Bottiglieri T. Folate, vitamin B12, and homocysteine in major depressive disorder. Am J Psychiatry 1997; 154:426-28.
123. Coppen A, Abou-Saleh MT. Plasma folate and affective morbidity during long-term lithium therapy. Br J Psychiatry 1982; 141:87-89.
124. Godfrey PS, Toone BK, Carney MW, Flynn TG, Bottiglieri T, Laundy M, Chanarin I, Reynolds EH. Enhancement of recovery from psychiatric illness by methylfolate. Lancet 1990; 336:392-95.
125. Coppen A, Bailey J. Enhancement of the antidepressant action of fluoxetine by folic acid: A randomised, placebo controlled trial. J Affect Disord 2000; 60:121-30.
126. Bottiglieri T. Homocysteine and folate metabolism in depression. Prog Neuropsycho-pharmacol Biol Psychiatry 2005; 29:1103-12.
127. Beetstra S, Thomas P, Salisbury C, Turner J, Fenech M. Folic acid deficiency increases chromosomal instability, chromosome 21 aneuploidy and sensitivity to radiation-induced micronuclei. Mutat Res 2005; 578:317-26.
128. Kruman II, Schwartz E, Kruman Y, Cutler RG, Zhu X, Greig NH, Mattson MP. Suppression of uracil-DNA glycosylase induces neuronal apoptosis. J Biol Chem 2004; 279:43952-60.
129. Gobbel GT, Bellinzona M, Vogt AR, Gupta N, Fike JR, Chan PH. Response of postmitotic neurons to X-irradiation: Implications for the role of DNA damage in neuronal apoptosis. J Neurosci 1998; 18:147-55.
130. Weissman L, de Souza-Pinto NC, Stevnsner T, Bohr VA. DNA repair, mitochondria, and neurodegeneration. Neuroscience 2007; 145(4):1318-29.
131. Goulian M, Bleile B, Tseng BY. The effect of methotrexate on levels of dUTP in animal cells. J Biol Chem 1980; 255:10630-37.
132. Goulian M, Bleile B, Tseng BY. Methotrexate-induced misincorporation of uracil into DNA. Proc Natl Acad Sci USA 1980; 7:1956-60.
133. Bertino JR, Mini E, Fernandes DJ. Sequential methotrexate and 5-fluorouracil: Mechanisms of synergy. Semin Oncol 1983; 10(Suppl 2):2-5.
134. Kruman II, Kumaravel TS, Lohani A, Pedersen WA, Cutler RG, Kruman Y, Haughey N, Lee J, Evans M, Mattson MP. Folic acid deficiency and homocysteine impair DNA repair in hippocampal neurons and sensitize them to amyloid toxicity in experimental models of Alzheimer’s disease. J Neurosci 2002; 22:1752-62.
135. Kronenberg G, Harms C, Sobol RW, Cardozo-Pelaez F, Linhart H, Winter B, Balkaya M, et al. Folate deficiency induces neurodegeneration and brain dysfunction in mice lacking uracil DNA glycosylase. J Neurosci 2008; 28:7219-30.
136. Lu Y, Christian K, Lu B. BDNF: A key regulator for protein synthesis-dependent LTP and long-term memory? Neurobiol Learn Mem 2008; 89:312-23.
137. Hu Y, Russek SJ. BDNF and the diseased nervous system: A delicate balance between adaptive and pathological processes of gene regulation. JNeurochem 2008; 105:1-17.
138. McCully KS. Homocysteine, vitamins, and vascular disease prevention. Am J Clin Nutr2007; 86:1563S-68S.
139. Wilson KM, Lentz SR. Mechanisms of the atherogenic effects of elevated homocysteine in experimental models. Semin Vasc Med 2005; 5:163-71.
140. Lentz SR. Mechanisms of homocysteine-induced atherothrombosis. J Thromb Haemost2005; 3:1646-54.
141. Cook JW, Taylor LM, Orloff SL, Landry GJ, Moneta GL, Porter JM. Homocysteine and arterial disease. Experimental mechanisms. Vascul Pharmacol 2002; 38:293-300.
142. Dayal S, Arning E, Bottiglieri T, Böger RH, Sigmund CD, Faraci FM, Lentz SR. Cerebral vascular dysfunction mediated by superoxide in hyperhomocysteinemic mice. Stroke 2004; 35:1957-62.
143. Dayal S, Bottiglieri T, Arning E, Maeda N, Malinow MR, Sigmund CD, Heistad DD, Faraci FM, Lentz SR. Endothelial dysfunction and elevation of S-adenosylhomocysteine in cystathionine beta-synthase-deficient mice. Circ Res 2001; 88:1203-09.
144. Lipton SA, Kim WK, Choi YB, Kumar S, D’Emilia DM, Rayudu PV, Arnelle DR, Stamler JS. Neurotoxicity associated with dual actions of homocysteine at the N-methyl-D-aspartate receptor. Proc Natl Acad Sci USA 1997; 94:5923-28.
145. Olney JW. Excitatory amino acids and neuropsychiatrie disorders. Biol Psychiatry 1989; 26:505-25.
146. Do KQ, Benz B, Binns KE, Eaton SA, Salt TE. Release of homocysteic acid from rat thalamus following stimulation of somatosensory afferents in vivo: Feasibility of glial participation in synaptic transmission. Neuroscience 2004; 124:387-93.
147. Cuenod M, Grandes P, Zangerle L, Streit P, Do KQ. Sulphur-containing excitatory amino acids in intercellular communication. Biochem Soc Trans 1993; 21:72-77.
148. Lazarewicz J, Urbanska EM. Dual effect of DL-homocysteine and S-adenosylhomo-cysteine on brain synthesis of the glutamate receptor antagonist, kynurenic acid. J Neurosci Res 2005; 79:375-82.
149. Zieminska E, Stafiej A, Lazarewicz JW. Role of group I metabotropic glutamate receptors and NMDA receptors in homocysteine-evoked acute neurodegeneration of cultured cerebellar granule neurones. Neurochem Int 2003; 43:481-92.
150. Luchowska E, Luchowski P, Paczek R, Ziembowicz A, Kocki T, Turski WA, Wielosz M, Azarewicz J, Urbanska EM. Dual effect of DL-homocysteine and S-adenosylhomo-cysteine on brain synthesis of the glutamate receptor antagonist, kynurenic acid. JNeurosci Res 2005; 79:375-82.
151. Surtees R, Bowron A, Leonard J. Cerebrospinal fluid and plasma total homocysteine and related metabolites in children with cystathionine beta-synthase deficiency: The effect of treatment. Pediatr Res 1997; 42:577-82.
152. Quinn CT, Griener JC, Bottiglieri T, Hyland K, Farrow A, Kamen BA. Elevation of homocysteine and excitatory amino acid neurotransmitters in the CSF of children who receive methotrexate for the treatment of cancer. J Clin Oncol 1997; 15:2800-06.
153. Quinn CT, Griener JC, Bottiglieri T, Arning E, Winick NJ. Effects of intraventricular methotrexate on folate, adenosine, and homocysteine metabolism in cerebrospinal fluid. J Pediatr Hematol Oncol 2004; 26:386-88.
154. Hasegawa T, Ukai W, Jo DG, Xu X, Mattson MP, Nakagawa M, Araki W, Saito T, Yamada T. Homocysteic acid induces intraneuronal accumulation of neurotoxic Abeta42: Implications for the pathogenesis of Alzheimer’s disease. J Neurosci Res2005; 80:869-76.
155. Bains JS, Shaw CA. Neurodegenerative disorders in humans: The role of glutathione in oxidative stress-mediated neuronal death. Brain Res Brain Res Rev 1997; 25:335-58.
156. White AR, Huang X, Jobling MF, Barrow CJ, Beyreuther K, Masters CL, Bush AI, Cappai R. Homocysteine potentiates copper- and amyloid beta peptide-mediated toxicity in primary neuronal cultures: Possible risk factors in the Alzheimer’s-type neurodegenerative pathways. J Neurochem 2001; 76:1509-20.
157. Ho PI, Ashline D, Dhitavat S, Ortiz D, Collins SC, Shea TB, Rogers E. Folate deprivation induces neurodegeneration: Roles of oxidative stress and increased homocysteine. Neurobiol Dis 2003; 14:32-42.
158. Wyse AT, Zugno AI, Streck EL, Matté C, Calcagnotto T, Wannmacher CM, Wajner M. Inhibition of Na(+), K(+)-ATPase activity in hippocampus of rats subjected to acute administration of homocysteine is prevented by vitamins E and C treatment. Neurochem Res 2002; 27:1685-89.
159. Matté C, Mackedanz V, Stefanello FM, Scherer EB, Andreazza AC, Zanotto C, Moro AM, et al. Chronic hyperhomocysteinemia alters antioxidant defenses and increases DNA damage in brain and blood of rats: Protective effect of folic acid. Neurochem Int 2009; 54:7-13.
160. Selley ML, Close DR, Stern SE. The effect of increased concentrations of homocysteine on the concentration of (E)-4-hydroxy-2-nonenal in the plasma and cerebrospinal fluid of patients with Alzheimer’s disease. Neurobiol Aging 2002; 23:383-88.