Methionine supplementation enhances learning and rescues depression through epigenetic regulation of hippocampal Bdnf. (c2018)

Abstract

Brain-derived neurotrophic factor (BDNF) is essential for synaptic plasticity and learning and memory formation. It has been previously shown that the expression of BDNF is epigenetically regulated through histone methylation. Methionine, an amino acid obtained from the diet, is the precursor of S-adenosylmethionine (SAM), which is the major methyl donor in most methylation reactions. In this study, the effect of methionine supplementation on BDNF expression was assessed. Methionine treatment (100 μM) induced BDNF promoter I (pI) and coding mRNA expression in primary neuronal cell cultures. Treatment also activated Tropomyosin-related Kinase B (TrkB) signaling. Learning and memory were assessed using the Morris Water Maze. 6-Week-old C57BL/6 male mice intraperitoneally injected with a combination of 1.55175 mg/Kg methionine and 80 μg/Kg folic acid (FA), which allows regeneration of methionine, exhibited improved learning. Additionally, mice treated with methionine showed enhanced short-term memory. Inhibition of TrkB signaling led to a loss of this positive effect. These results suggest that methionine intake could enhance learning and memory possibly through modifying methylation marks in the brain and that this enhancement is mediated through BDNF, which is upregulated upon methionine treatment.