Neuronal Activity-Induced Gadd45b Promotes Epigenetic DNA Demethylation and Adult Neurogenesis

Neuronal Activity-Induced Gadd45b Promotes Epigenetic DNA Demethylation and Adult Neurogenesis

2009 February 20; 323(5917): 1074–1077 | Dengke K. Ma, Mi-Hyeon Jang, Junjie U. Guo, Yasuji Kitabatake, Min-lin Chang, Nattapol Pow-anpongkul, Richard A. Flavell, Binfeng Lu, Guo-li Ming, Hongjun Song
The study identifies *Gadd45b* as a neural activity-induced immediate early gene in mature hippocampal neurons. Mice lacking *Gadd45b* exhibit specific deficits in neural activity-induced proliferation of neural progenitors and dendritic growth of newborn neurons in the adult hippocampus. Mechanistically, *Gadd45b* is required for activity-induced DNA demethylation of specific promoters and expression of genes critical for adult neurogenesis, such as brain-derived neurotrophic factor (BDNF) and fibroblast growth factor (FGF). The findings suggest that *Gadd45b* links neuronal circuit activity to epigenetic DNA modification and expression of secreted factors in mature neurons, thereby modulating neurogenesis in the adult brain.The study identifies *Gadd45b* as a neural activity-induced immediate early gene in mature hippocampal neurons. Mice lacking *Gadd45b* exhibit specific deficits in neural activity-induced proliferation of neural progenitors and dendritic growth of newborn neurons in the adult hippocampus. Mechanistically, *Gadd45b* is required for activity-induced DNA demethylation of specific promoters and expression of genes critical for adult neurogenesis, such as brain-derived neurotrophic factor (BDNF) and fibroblast growth factor (FGF). The findings suggest that *Gadd45b* links neuronal circuit activity to epigenetic DNA modification and expression of secreted factors in mature neurons, thereby modulating neurogenesis in the adult brain.
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[slides and audio] Neuronal Activity%E2%80%93Induced Gadd45b Promotes Epigenetic DNA Demethylation and Adult Neurogenesis