Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Environmental Enrichment and Fluoxetine Neurogenic Stimuli Increase ß3-Tubulin Immature Neurons in Meninges Through Trkb-Mediated Signaling

Stefania Zorzin
ORCID logo ,
Andrea Corsi
,
Annachiara Pino
,
Alessia Amenta
,
Guido Francesco Fumagalli
ORCID logo ,
Cristiano Chiamulera
,
Francesco Bifari
ORCID logo ,
Ilaria Decimo
* ORCID logo
Version 1 : Received: 5 June 2021 / Approved: 11 June 2021 / Online: 11 June 2021 (16:55:45 CEST)

A peer-reviewed article of this Preprint also exists.

Zorzin, S.; Corsi, A.; Ciarpella, F.; Bottani, E.; Dolci, S.; Malpeli, G.; Pino, A.; Amenta, A.; Fumagalli, G.F.; Chiamulera, C.; Bifari, F.; Decimo, I. Environmental Enrichment Induces Meningeal Niche Remodeling through TrkB-Mediated Signaling. Int. J. Mol. Sci. 2021, 22, 10657. Zorzin, S.; Corsi, A.; Ciarpella, F.; Bottani, E.; Dolci, S.; Malpeli, G.; Pino, A.; Amenta, A.; Fumagalli, G.F.; Chiamulera, C.; Bifari, F.; Decimo, I. Environmental Enrichment Induces Meningeal Niche Remodeling through TrkB-Mediated Signaling. Int. J. Mol. Sci. 2021, 22, 10657.

Abstract

Neural precursors (NPs) present in the hippocampus can be modulated by several neurogenic stimuli including environmental enrichment (EE) and antidepressant treatment acting through BDNF-TrkB signaling. We have recently identified NPs in meninges, however menigneal niche response to pro-neurogenic stimuli has never been investigated. To this aim, we analyzed the effects of 4 weeks fluoxetine administration or 1 week EE treatment on NP distribution in mouse brain meninges. Following neurogenic stimuli, although we did not detect modification of meningeal cell number and proliferation, we observed, in meninges, an increased number of β3-Tubulin+ immature neuronal cells. Lineage-tracing experiment confirmed that EE-induced β3-Tubulin+ immature neuronal cells present in meninges originated from GLAST+ radial glia cells. To investigate the molecular mechanism responsible for this response, we studied the BDNF-TrkB interaction. Treatment with ANA-12, a TrkB non-competitive inhibitor, abolished the EE-induced increase of β3-Tubulin+ immature neuronal cells in meninges.Overall these data showed, for the first time, that the meningeal niche responded to neurogenic stimuli by increasing the immature neuronal population through TrkB-mediated signaling. A better understanding of the neurogenic stimuli effects on NPs in meninges may be useful to improve the effectiveness of depression and mood disorders treatments.

Keywords

neurogenesis; TrkB; BDNF; meninges; ANA-12; neural cell differentiation

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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