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Mol Genet Metab Rep. 2015 Feb 20;3:1-4. doi: 10.1016/j.ymgmr.2015.02.001. eCollection 2015 Jun.

Methylenetetrahydrofolate reductase deficiency alters levels of glutamate and γ-aminobutyric acid in brain tissue.

Author information

1
Department of Experimental Neurology, Center for Stroke Research Berlin, Charité University Medicine Berlin, Germany.
2
Department of Experimental Psychiatry, University Hospital Carl Gustav Carus, Technische Universitaet Dresden, Dresden, Germany.
3
Department of Experimental Neurology, Center for Stroke Research Berlin, Charité University Medicine Berlin, Germany; German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.

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.

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

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