Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/109147
Title: | Involvement of calpains in adult neurogenesis: implications for stroke | Authors: | Machado, Vanessa M. Morte, Maria I. Carreira, Bruno P. Azevedo, Maria M. Takano, Jiro Iwata, Nobuhisa Saido, Takaomi C. Asmussen, Hannelore Horwitz, Alan R. Carvalho, Caetana M. Araújo, Inês M. |
Keywords: | calpains; calpastatin; hippocampus; migration; neurogenesis; proliferation; stroke; subventricular zone | Issue Date: | 2015 | Publisher: | Frontiers Media S.A. | Project: | PTDC/SAU-NMC/112183/2009 PEst-OE/EQB/LA0023/2013-2014 SFRH/BPD/78901/2011 SFRH/BD/38127/2007 SFRH/BD/78050/2011 PEst-C/SAU/LA0001/2013 |
Serial title, monograph or event: | Frontiers in Cellular Neuroscience | Volume: | 9 | Issue: | FEB | Abstract: | Calpains are ubiquitous proteases involved in cell proliferation, adhesion and motility. In the brain, calpains have been associated with neuronal damage in both acute and neurodegenerative disorders, but their physiological function in the nervous system remains elusive. During brain ischemia, there is a large increase in the levels of intracellular calcium, leading to the activation of calpains. Inhibition of these proteases has been shown to reduce neuronal death in a variety of stroke models. On the other hand, after stroke, neural stem cells (NSC) increase their proliferation and newly formed neuroblasts migrate towards the site of injury. However, the process of forming new neurons after injury is not efficient and finding ways to improve it may help with recovery after lesion. Understanding the role of calpains in the process of neurogenesis may therefore open a new window for the treatment of stroke. We investigated the involvement of calpains in NSC proliferation and neuroblast migration in two highly neurogenic regions in the mouse brain, the dentate gyrus (DG) and the subventricular zone (SVZ). We used mice that lack calpastatin, the endogenous calpain inhibitor, and calpains were also modulated directly, using calpeptin, a pharmacological calpain inhibitor. Calpastatin deletion impaired both NSC proliferation and neuroblast migration. Calpain inhibition increased NSC proliferation, migration speed and migration distance in cells from the SVZ. Overall, our work suggests that calpains are important for neurogenesis and encourages further research on their neurogenic role. Prospective therapies targeting calpain activity may improve the formation of new neurons following stroke, in addition to affording neuroprotection. | URI: | https://hdl.handle.net/10316/109147 | ISSN: | 1662-5102 | DOI: | 10.3389/fncel.2015.00022 | Rights: | openAccess |
Appears in Collections: | I&D CNC - Artigos em Revistas Internacionais |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
Involvement of calpains in adult neurogenesis Implications for stroke.pdf | 1.57 MB | Adobe PDF | View/Open |
Page view(s)
69
checked on Oct 9, 2024
Download(s)
28
checked on Oct 9, 2024
Google ScholarTM
Check
Altmetric
Altmetric
This item is licensed under a Creative Commons License