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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 
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.
ISSN: 1662-5102
DOI: 10.3389/fncel.2015.00022
Rights: openAccess
Appears in Collections:I&D CNC - Artigos em Revistas Internacionais

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