title: Methylenetetrahydrofolate reductase deficiency alters levels of glutamate and γ-aminobutyric acid in brain tissue.
abstract: Methylenetetrahydrofolate reductase (MTHFR) is an enzyme key regulator in folate metabolism. Deficiencies in MTHFR result in increased levels of homocysteine, which leads to reduced levels of S-adenosylmethionine (SAM). In the brain, SAM donates methyl groups to catechol-O-methyltransferase (COMT), which is involved in neurotransmitter analysis. Using the MTHFR-deficient mouse model the purpose of this study was to investigate levels of monoamine neurotransmitters and amino acid levels in brain tissue. MTHFR deficiency affected levels of both glutamate and γ-aminobutyric acid in within the cerebellum and hippocampus. Mthfr (-/-) mice had reduced levels of glutamate in the amygdala and γ-aminobutyric acid in the thalamus. The excitatory mechanisms of homocysteine through activation of the N-methyl-d-aspartate receptor in brain tissue might alter levels of glutamate and γ-aminobutyric acid.
authors.affiliation: Department of Experimental Neurology, Center for Stroke Research Berlin, Charité University Medicine Berlin, Germany.
authors.forename: N M
authors.initials: NM
authors.lastname: Jadavji
authors.affiliation: Department of Experimental Psychiatry, University Hospital Carl Gustav Carus, Technische Universitaet Dresden, Dresden, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Wieske
authors.affiliation: Department of Experimental Neurology, Center for Stroke Research Berlin, Charité University Medicine Berlin, Germany; German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Dirnagl
authors.affiliation: Department of Experimental Psychiatry, University Hospital Carl Gustav Carus, Technische Universitaet Dresden, Dresden, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Winter
keywords: 5-HIAA, 5-hydroxyindoleacetic acid; 5-HT, serotonin.; 5-methylTHF, 5-methyltetrahydrofolate; COMT, catechol-O-methyltransferase; DOPAC, 3,4-dihydroxyphenylacetic acid; GABA, γ-aminobutyric acid; Glutamate; HPLC, high performance liquid chromatography; HVA, homovanillic acid; Homocysteine; MTHFR, methylenetetrahydrofolate reductase; Methylenetetrahydrofolate reductase; Monoamine neurotransmitters; S-Adenosylmethionine; SAM, S-adenosylmethionine; γ-Aminobutyric acid