Abstract
Methylenetetrahydrofolate reductase (MTHFR) deficiency is the most common genetic cause of hyperhomocysteinemia, which is associated with increased risk for cardiovascular disease, stroke and possibly other neurological disorders. Microarray analysis of brain RNA from day 14 Mthfr −/− mice revealed several genes with altered expression. Expression changes in inositol 1,4,5-triphosphate receptor, type 1 ( Itpr1), proteolipid protein ( Plp), neurogenic differentiation factor 1 ( Neurod1), S100 calcium binding protein A8 ( S100a8), and methylenetetrahydrofolate dehydrogenase (NAD+ dependent), methenyltetrahydrofolate cyclohydrolase ( Mthfd2) were confirmed by RT-PCR. We propose that neuronal damage by hyperhomocysteinemia may involve disruption of intracellular calcium.
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