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

By Dengke K. Ma, M. Jang, Junjie U. Guo, Yasuji Kitabatake, Min-lin Chang, Nattapol Pow-anpongkul, R. Flavell, B. Lu, Guo-li Ming, Hongjun Song. 2009

921 citations recorded by the source corpus.

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 long-lasting 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.

Subfields: Developmental Neuroscience, Genetics, Molecular Biology

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Citations in the corpus

Adult Neurogenesis in the Mammalian Brain: Significant Answers and Significant Questions (2011, background): “…promote BDNF and FGF1 expression in mature dentate granule cells in response to neuronal activation and deletion of Gadd45b reduces activity-induced proliferation of neural precursors and dendritic growth of newborn neurons in the adult hippocampus (Guo et al., 2011a; Ma et al., 2009).”
Adult neurogenesis modulates the hippocampus-dependent period of associative fear memory. (2009, background): “The level of adult hippocampal neurogenesis is positively and negatively modulated by environmental conditions, neuronal activity, aging, and stress (Lledo et al., 2006; Ma et al., 2009; Ming and Song, 2005; Zhao et al., 2008).”
Hydroxylation of 5-methylcytosine by TET1 promotes active DNA demethylation in the adult brain (2011, positive): “Our previous studies have shown that synchronous activation of adult dentate granule neurons in vivo by electroconvulsive stimulation (ECS) leads to CpG demethylation of Bdnf IX and Fgf1B promoters in these neurons within 4 hr but has no effect on the Fgf1G promoter (Ma et al., 2009b).”
The role of adult hippocampal neurogenesis in brain health and disease (2018, positive): “A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript Table 1 Signals regulating adult hippocampal neurogenesis Stages Regulators Secreted factors and downstream effectors (Morphogens, growth fa”
Adult Neurogenesis in the Hippocampus: From Stem Cells to Behavior. (2016, positive): “…adult neurogenesis, especially concerning maintenance and exit from quiescence in adult NSCs. Interestingly, DNA demethylation appears to be induced by neuronal activity in the DG, resulting in the proliferation of neural progenitors and growth of newborn DGCs (Guo et al., 2011a; Ma et al., 2009).”
Reversing DNA Methylation: Mechanisms, Genomics, and Biological Functions (2014, neutral): “Furthermore, Gadd45a- and Gadd45b null mice are grossly normal and have no global alteration in DNA methylation levels (Engel et al., 2009; Ma et al., 2009).”