期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 19, 页码 -出版社
MDPI
DOI: 10.3390/ijms221910657
关键词
neurogenesis; TrkB; BDNF; meninges; ANA-12; meningeal niche; radial glia cell; neural precursor; enriched environment; EE; ENR
资金
- Fondazione Cariverona [2017-0604]
- Fondazione Italiana Sclerosi multipla (FISM) [2017/R/11]
- European Union [824164]
- Fondazione Telethon-Italy [GGP19250, GSP20004_PAsMCT8006]
- italian patient association la Colonna, GALM
The study revealed that environmental enrichment (EE) stimulus can modulate neural precursor cell distribution in meninges through BDNF-TrkB signaling, highlighting the importance of environmental stimuli on brain regeneration. The findings suggest that the meningeal niche could respond to pharmacological neurogenic stimuli, potentially offering new avenues for enhancing treatments for neurodegenerative and neuropsychiatric disorders.
Neural precursors (NPs) present in the hippocampus can be modulated by several neurogenic stimuli, including environmental enrichment (EE) acting through BDNF-TrkB signaling. We have recently identified NPs in meninges; however, the meningeal niche response to pro-neurogenic stimuli has never been investigated. To this aim, we analyzed the effects of EE exposure on NP distribution in mouse brain meninges. Following neurogenic stimuli, although we did not detect modification of the meningeal cell number and proliferation, we observed an increased number of neural precursors in the meninges. A lineage tracing experiment suggested that EE-induced beta 3Tubulin(+) immature neuronal cells present in the meninges originated, at least in part, from GLAST(+) radial glia cells. To investigate the molecular mechanism responsible for meningeal reaction to EE exposure, we studied the BDNF-TrkB interaction. Treatment with ANA-12, a TrkB non-competitive inhibitor, abolished the EE-induced meningeal niche changes. Overall, these data showed, for the first time, that EE exposure induced meningeal niche remodeling through TrkB-mediated signaling. Fluoxetine treatment further confirmed the meningeal niche response, suggesting it may also respond to other pharmacological neurogenic stimuli. A better understanding of the neurogenic stimuli modulation for meninges may be useful to improve the effectiveness of neurodegenerative and neuropsychiatric treatments.
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