Glycine N-methyltransferase expression in the hippocampus and its role in neurogenesis and cognitive performance.
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.
['Carrasco|Manuel|M|', 'Rabaneda|Luis G|LG|', 'Murillo-Carretero|Maribel|M|', 'Ortega-Martínez|Sylvia|S|', 'Martínez-Chantar|María L|ML|', 'Woodhoo|Ashwin|A|', 'Luka|Zigmund|Z|', 'Wagner|Conrad|C|', 'Lu|Shelly C|SC|', 'Mato|José M|JM|', 'Micó|Juan A|JA|', 'Castro|Carmen|C|']
D000592:Amino Acid Metabolism, Inborn Errors D000818:Animals D003071:Cognition D019927:Cyclin E D016222:Fibroblast Growth Factor 2 D005786:Gene Expression Regulation D050938:Glycine N-Methyltransferase D006624:Hippocampus D020935:MAP Kinase Signaling System D018782:Maze Learning D008569:Memory Disorders D008715:Methionine D008716:Methionine Adenosyltransferase D008745:Methylation D051379:Mice D008810:Mice, Inbred C57BL D018345:Mice, Knockout D009419:Nerve Tissue Proteins D055495:Neurogenesis D009473:Neuronal Plasticity D045442:Rotarod Performance Test D012436:S-Adenosylmethionine
glycine N-methyltransferase neurogenesis learning memory S-adenosylmethionine neural progenitor cells