Title: RGS6 mediates effects of voluntary running on adult hippocampal neurogenesis
Legend: We used cell type-specific RiboTag-seq to unveil voluntary running induces gene expression changes specifically within the adult-born hippocampal neurons. We have identified the regulator of G protein signaling 6 (RGS6) as a key factor that mediates running-enhanced maturation and plasticity of adult-born neuron and running-mediated cognitive improvement.
Citation: Gao Y, Shen M, Gonzalez JC, Dong Q, Kannan S, Hoang JT, Eisinger BE, Pandey J, Javadi S, Chang Q, Wang D, Overstreet-Wadiche L, Zhao X. (2020). RGS6 Mediates Effects of Voluntary Running on Adult Hippocampal Neurogenesis. Cell Reports, 32(8):108114. doi: 10.1016/j.celrep.2020.108114. Erratum for: Cell Rep. 2020 Aug 4;32(5):107997. PMID: 32846117; PMCID: PMC7521437.
Abstract: Voluntary running enhances adult hippocampal neurogenesis, with consequences for hippocampal-dependent learning ability and mood regulation. However, the underlying mechanism remains unclear. Here, we show that voluntary running induces unique and dynamic gene expression changes specifically within the adult-born hippocampal neurons, with significant impact on genes involved in neuronal maturation and human diseases. We identify the regulator of G protein signaling 6 (RGS6) as a key factor that mediates running impact on adult-born neurons. RGS6 overexpression mimics the positive effects of voluntary running on morphological and physiological maturation of adult new neurons and reduced sensitivity of adult-born neurons to the inhibitory effect of GABAB (γ-Aminobutyric acid B) receptor activation. Knocking down RGS6 abolishes running-enhanced neuronal maturation and hippocampal neurogenesis-dependent learning and anxiolytic effect. Our study provides a data resource showing genome-wide intrinsic molecular changes in adult-born hippocampal neurons that contribute to voluntary running-induced neurogenesis.
About the Lab: Research in the Zhao laboratory focuses on understanding the molecular mechanisms that regulate neural stem cells and neurodevelopment with the goal of applying this knowledge for the treatment of neurological disorders and injuries. Neurodevelopmental disorders are a highly heterogeneous constellation of disorders, both in terms of etiology and clinical manifestations. Using neural stem cells as model systems, the lab is investigating the molecular mechanisms that regulate neuronal development during the postnatal period and their implications in human neurodevelopmental disorders such as Rett syndrome, autism, and fragile X syndrome.