Glycine N-methyltransferase expression in the hippocampus and its role in neurogenesis and cognitive performance.

Carrasco M, Rabaneda LG, Murillo-Carretero M, Ortega-Martínez S, Martínez-Chantar ML, Woodhoo A, Luka Z, Wagner C, Lu SC, Mato JM, Micó JA, Castro C
Hippocampus. 2014 24 (7): 840-52

PMID: 24687756 · PMCID: PMC4065208 · DOI:10.1002/hipo.22274

The hippocampus is a brain area characterized by its high plasticity, observed at all levels of organization: molecular, synaptic, and cellular, the latter referring to the capacity of neural precursors within the hippocampus to give rise to new neurons throughout life. Recent findings suggest that promoter methylation is a plastic process subjected to regulation, and this plasticity seems to be particularly important for hippocampal neurogenesis. We have detected the enzyme GNMT (a liver metabolic enzyme) in the hippocampus. GNMT regulates intracellular levels of SAMe, which is a universal methyl donor implied in almost all methylation reactions and, thus, of prime importance for DNA methylation. In addition, we show that deficiency of this enzyme in mice (Gnmt-/-) results in high SAMe levels within the hippocampus, reduced neurogenic capacity, and spatial learning and memory impairment. In vitro, SAMe inhibited neural precursor cell division in a concentration-dependent manner, but only when proliferation signals were triggered by bFGF. Indeed, SAMe inhibited the bFGF-stimulated MAP kinase signaling cascade, resulting in decreased cyclin E expression. These results suggest that alterations in the concentration of SAMe impair neurogenesis and contribute to cognitive decline.

© 2014 Wiley Periodicals, Inc.

MeSH Terms (22)

Amino Acid Metabolism, Inborn Errors Animals Cognition Cyclin E Fibroblast Growth Factor 2 Gene Expression Regulation Glycine N-Methyltransferase Hippocampus MAP Kinase Signaling System Maze Learning Memory Disorders Methionine Methionine Adenosyltransferase Methylation Mice Mice, Inbred C57BL Mice, Knockout Nerve Tissue Proteins Neurogenesis Neuronal Plasticity Rotarod Performance Test S-Adenosylmethionine

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