Physical exercise rescues defective neural stem cells and neurogenesis in the adult subventricular zone of Btg1 knockout mice

Valentina Mastrorilli, Chiara Scopa, Daniele Saraulli, Marco Costanzi, Raffaella Scardigli, Jean Pierre Rouault, Stefano Farioli-Vecchioli, Felice Tirone

Research output: Contribution to journalArticle

Abstract

Adult neurogenesis occurs throughout life in the dentate gyrus (DG) and the subventricular zone (SVZ), where glia-like stem cells generate new neurons. Voluntary running is a powerful neurogenic stimulus triggering the proliferation of progenitor cells in the DG but, apparently, not in the SVZ. The antiproliferative gene Btg1 maintains the quiescence of DG and SVZ stem cells. Its ablation causes intense proliferation of DG and SVZ stem/progenitor cells in young mice, followed, during adulthood, by progressive decrease of the proliferative capacity. We have previously observed that running can rescue the deficit of DG Btg1-null neurogenesis. Here, we show that in adult Btg1-null SVZ stem and neuroblast cells, the reduction of proliferation is associated with a longer cell cycle and a more frequent entry into quiescence. Notably, running increases proliferation in Btg1-null SVZ stem cells highly above the levels of sedentary wild-type mice and restores normal values of cell cycle length and quiescence in stem and neuroblast cells, without affecting wild-type cells. Btg1-null SVZ neuroblasts show also increased migration throughout the rostral migratory stream and a deficiency of differentiated neurons in the olfactory bulb, possibly a consequence of premature exit from the cycle; running, however, normalizes migration and differentiation, increasing newborn neurons recruited to the olfactory circuitry. Furthermore, running increases the self-renewal of Btg1-null SVZ-derived neurospheres and, remarkably, in aged Btg1-null mice almost doubles the proliferating SVZ stem cells. Altogether, this reveals that SVZ stem cells are endowed with a hidden supply of self-renewal capacity, coupled to cell cycle acceleration and emerging after ablation of the quiescence-maintaining Btg1 gene and following exercise.

Original languageEnglish
Pages (from-to)2855-2876
Number of pages22
JournalBrain Structure and Function
Volume222
Issue number6
DOIs
Publication statusPublished - Aug 1 2017

Keywords

  • Adult neurogenesis
  • Cell cycle kinetics
  • Differentiation
  • Neural stem/progenitor cells
  • Proliferation
  • Running

ASJC Scopus subject areas

  • Anatomy
  • Neuroscience(all)
  • Histology

Fingerprint Dive into the research topics of 'Physical exercise rescues defective neural stem cells and neurogenesis in the adult subventricular zone of Btg1 knockout mice'. Together they form a unique fingerprint.

  • Cite this

    Mastrorilli, V., Scopa, C., Saraulli, D., Costanzi, M., Scardigli, R., Rouault, J. P., Farioli-Vecchioli, S., & Tirone, F. (2017). Physical exercise rescues defective neural stem cells and neurogenesis in the adult subventricular zone of Btg1 knockout mice. Brain Structure and Function, 222(6), 2855-2876. https://doi.org/10.1007/s00429-017-1376-4