RGS6 Mediates Effects of Voluntary Running on Adult Hippocampal Neurogenesis

Cell Rep. 2020 Aug 4;32(5):107997. doi: 10.1016/j.celrep.2020.107997.

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.

Keywords: GABA; Rgs6; RiboTag-seq; adult neurogenesis; anxiety; gene expression; hippocampus; learning; neuronal maturation; voluntary running.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism*
  • Animals
  • Anxiety / physiopathology
  • Cell Differentiation
  • Gene Expression Regulation
  • Hippocampus / metabolism*
  • Humans
  • Memory
  • Mice, Inbred C57BL
  • Neurogenesis* / genetics
  • Neurons / metabolism
  • Physical Conditioning, Animal*
  • RGS Proteins / genetics
  • RGS Proteins / metabolism*
  • Receptors, GABA-B / metabolism

Substances

  • RGS Proteins
  • Receptors, GABA-B
  • Rgs6 protein, mouse