Hippocampal epigenetic modification at the brain-derived neurotrophic factor gene induced by an enriched environment.
Environmental enrichment is an experimental paradigm that increases brain-derived neurotrophic factor (BDNF) gene expression accompanied by neurogenesis in the hippocampus of rodents. In the present study, we investigated whether an enriched environment could cause epigenetic modification at the BDNF gene in the hippocampus of mice. Exposure to an enriched environment for 3-4 weeks caused a dramatic increase in the mRNA expression of BDNF, but not platelet-derived growth factor A (PDGF-A), PDGF-B, vascular endothelial growth factor (VEGF), nerve growth factor (NGF), epidermal growth factor (EGF), or glial fibrillary acidic protein (GFAP), in the hippocampus of mice. Under these conditions, exposure to an enriched environment induced a significant increase in histone H3 lysine 4 (H3K4) trimethylation at the BDNF P3 and P6 promoters, in contrast to significant decreases in histone H3 lysine 9 (H3K9) trimethylation at the BDNF P4 promoter and histone H3 lysine 27 (H3K27) trimethylation at the BDNF P3 and P4 promoters without any changes in the expression of their associated histone methylases and demethylases in the hippocampus. The expression levels of several microRNAs in the hippocampus were not changed by an enriched environment. These results suggest that an enriched environment increases BDNF mRNA expression via sustained epigenetic modification in the mouse hippocampus.
Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Shinagawa-ku, Tokyo, Japan.
Naoko
N
Kuzumaki
Daigo
D
Ikegami
Rie
R
Tamura
Nana
N
Hareyama
Satoshi
S
Imai
Michiko
M
Narita
Kazuhiro
K
Torigoe
Keiichi
K
Niikura
Hideyuki
H
Takeshima
Takayuki
T
Ando
Katsuhide
K
Igarashi
Jun
J
Kanno
Toshikazu
T
Ushijima
Tsutomu
T
Suzuki
Minoru
M
Narita
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D004777:Environment; D004815:Epidermal Growth Factor / Q000235:genetics; D044127:Epigenesis, Genetic; D018507:Gene Expression Regulation, Developmental; D005904:Glial Fibrillary Acidic Protein; D006624:Hippocampus / Q000254:growth & development / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020932:Nerve Growth Factor / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D055495:Neurogenesis / Q000235:genetics; D010982:Platelet-Derived Growth Factor / Q000235:genetics; D011401:Promoter Regions, Genetic; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
D019208:Brain-Derived Neurotrophic Factor; D005904:Glial Fibrillary Acidic Protein; D006657:Histones; D009419:Nerve Tissue Proteins; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C528900:glial fibrillary astrocytic protein, mouse; C075278:platelet-derived growth factor A; C467480:vascular endothelial growth factor A, mouse; D004815:Epidermal Growth Factor; D020932:Nerve Growth Factor