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 Vecchioli

Research output: Contribution to journalArticle

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.

Original languageEnglish
JournalMolecular Neurobiology
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Neural Stem Cells
Lateral Ventricles
Neurogenesis
Knockout Mice
Running
Olfactory Bulb
Neurons
Intrinsic Factor
Short-Term Memory
Brain Stem
Cell Cycle
Maintenance

Keywords

  • Adult neurogenesis
  • Cell cycle
  • Olfactory behavior
  • p21
  • Physical activity
  • Subventricular zone

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

Running-Activated Neural Stem Cells Enhance Subventricular Neurogenesis and Improve Olfactory Behavior in p21 Knockout Mice. / Nicolis di Robilant, Vittoria; Scardigli, Raffaella; Strimpakos, Georgios; Tirone, Felice; Middei, Silvia; Scopa, Chiara; De Bardi, Marco; Battistini, Luca; Saraulli, Daniele; Farioli Vecchioli, Stefano.

In: Molecular Neurobiology, 01.01.2019.

Research output: Contribution to journalArticle

Nicolis di Robilant, Vittoria ; Scardigli, Raffaella ; Strimpakos, Georgios ; Tirone, Felice ; Middei, Silvia ; Scopa, Chiara ; De Bardi, Marco ; Battistini, Luca ; Saraulli, Daniele ; Farioli Vecchioli, Stefano. / Running-Activated Neural Stem Cells Enhance Subventricular Neurogenesis and Improve Olfactory Behavior in p21 Knockout Mice. In: Molecular Neurobiology. 2019.
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