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Glycine N ‐methyltransferase expression in the hippocampus and its role in neurogenesis and cognitive performance
Author(s) -
Carrasco Manuel,
Rabaneda Luis G.,
MurilloCarretero Maribel,
OrtegaMartínez Sylvia,
MartínezChantar María L.,
Woodhoo Ashwin,
Luka Zigmund,
Wagner Conrad,
Lu Shelly C.,
Mato José M.,
Micó Juan A.,
Castro Carmen
Publication year - 2014
Publication title -
hippocampus
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.767
H-Index - 155
eISSN - 1098-1063
pISSN - 1050-9631
DOI - 10.1002/hipo.22274
Subject(s) - neurogenesis , hippocampus , hippocampal formation , neuroscience , neural stem cell , synaptic plasticity , dna methylation , neuroplasticity , kinase , chemistry , microbiology and biotechnology , psychology , biology , biochemistry , gene expression , stem cell , receptor , gene
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.