Neuronal activity-induced Gadd45b promotes epigenetic DNA demethylation and adult neurogenesis

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

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Abstract

The mammalian brain exhibits diverse types of neural plasticity, including activity-dependent neurogenesis in the adult hippocampus. How transient activation of mature neurons leads to longlasting modulation of adult neurogenesis is unknown. Here we identify Gadd45b as a neural activity-induced immediate early gene in mature hippocampal neurons. Mice with Gadd45b deletion 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 corresponding genes critical for adult neurogenesis, including brain-derived neurotrophic factor and fibroblast growth factor. Thus, Gadd45b links neuronal circuit activity to epigenetic DNA modification and expression of secreted factors in mature neurons for extrinsic modulation of neurogenesis in the adult brain.

Original languageEnglish (US)
Pages (from-to)1074-1077
Number of pages4
JournalScience
Volume323
Issue number5917
DOIs
StatePublished - Feb 20 2009

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Cite this

Ma, D. K., Jang, M. H., Guo, J. U., Kitabatake, Y., Chang, M. L., Pow-anpongkul, N., Flavell, R. A., Lu, B., Ming, G. L., & Song, H. (2009). Neuronal activity-induced Gadd45b promotes epigenetic DNA demethylation and adult neurogenesis. Science, 323(5917), 1074-1077. https://doi.org/10.1126/science.1166859