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Running-Activated Neural Stem Cells Enhance Subventricular Neurogenesis and Improve Olfactory Behavior in p21 Knockout Mice

  • Vittoria Nicolis di Robilant
  • Raffaella Scardigli
  • Georgios Strimpakos
  • Felice Tirone
  • Silvia Middei
  • Chiara Scopa
  • Marco De Bardi
  • Luca Battistini
  • Daniele Saraulli
  • Stefano Farioli VecchioliEmail author
Article

Abstract

In the subventricular zone (SVZ) of the adult brain, the neural stem cells (NSCs) ensure a continuous supply of new neurons to the olfactory bulb (OB), playing a key role in its plasticity and olfactory-related behavior. The activation and expansion of NSCs within the SVZ are finely regulated by environmental and intrinsic factors. Running represents one of the most powerful neurogenic stimuli, although is ineffective in enhancing SVZ neurogenesis. The cell cycle inhibitor p21 is an intrinsic inhibitor of NSCs’ expansion through the maintenance of their quiescence and the restrain of neural progenitor proliferation. In this work, we decided to test whether running unveils the intrinsic neurogenic potential of p21-lacking NSCs. To test this hypothesis, we examined the effect of three different paradigms of voluntary running (5, 12, and 21 days) on SVZ neurogenesis of p21 knockout (KO) male mice at two different stages of development, 2 and 12 months of age. In vivo and in vitro data clearly demonstrate that physical activity is consistent with the activation and expansion of NSCs and with the enhancement of SVZ neurogenesis in p21 KO mice. We also found that 12 days of running contribute to the increase in the number of new neurons functionally active within the OB, which associates with an improvement in olfactory performance strictly dependent on adult SVZ neurogenesis, i.e., the odor detection threshold and short-term olfactory memory. These data suggest that in the adult SVZ of p21 KO mice, NSCs retain a high neurogenic potential, triggered by physical activity, with long-term consequences in olfactory-related behavior.

Keywords

Adult neurogenesis Subventricular zone Physical activity Cell cycle p21 Olfactory behavior 

Notes

Acknowledgements

This work was supported by Regione Lazio Project FILAS to Stefano Farioli Vecchioli.

Supplementary material

12035_2019_1590_MOESM1_ESM.pdf (3.9 mb)
ESM 1 (PDF 4042 kb)

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Vittoria Nicolis di Robilant
    • 1
  • Raffaella Scardigli
    • 2
  • Georgios Strimpakos
    • 1
  • Felice Tirone
    • 1
  • Silvia Middei
    • 1
  • Chiara Scopa
    • 2
  • Marco De Bardi
    • 3
  • Luca Battistini
    • 3
  • Daniele Saraulli
    • 1
  • Stefano Farioli Vecchioli
    • 1
    Email author
  1. 1.Institute of Cell Biology and NeurobiologyNational Research CouncilMonterotondo (RM)Italy
  2. 2.European Brain Research Institute (EBRI)RomeItaly
  3. 3.Laboratory of NeuroimmunologyFondazione Santa LuciaRomeItaly

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