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Involvement of calpains in adult neurogenesis: implications for stroke

2015-02Journal article Open Access
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dc.contributor.authorMachado, Vanessa M.
dc.contributor.authorMorte, Maria I.
dc.contributor.authorCarreira, Bruno P.
dc.contributor.authorAzevedo, Maria M.
dc.contributor.authorTakano, Jiro
dc.contributor.authorIwata, Nobuhisa
dc.contributor.authorSaido, Takaomi C.
dc.contributor.authorAsmussen, Hannelore
dc.contributor.authorHorwitz, Alan R.
dc.contributor.authorCarvalho, Caetana M.
dc.contributor.authorAraújo, Inês
dc.date.accessioned2018-12-07T14:53:03Z
dc.date.available2018-12-07T14:53:03Z
dc.date.issued2015-02
dc.description.abstractCalpains 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.
dc.description.sponsorshipFoundation for Science and Technology, (FCT, Portugal); COMPETE; FEDER [PTDC/SAU-NMC/112183/2009, PEst-C/SAU/LA0001/2013-2014, PEst-OE/EQB/LA0023/2013-2014]; NIH [GM 23244]; FCT [SFRH/BPD/78901/2011, SFRH/BD/38127/2007, SFRH/BD/78050/2011]
dc.description.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.doi10.3389/fncel.2015.00022
dc.identifier.issn1662-5102
dc.identifier.urihttp://hdl.handle.net/10400.1/11331
dc.language.isoeng
dc.peerreviewedyes
dc.publisherFrontiers Media Sa
dc.relationPHYSIOLOGICAL ROLE OF CALPAINS: HOW DO CALPAINS REGULATE CELL PROLIFERATION AND MIGRATION IN THE BRAIN
dc.relationEFFECTS OF THE PRENATAL/POSTNATAL EXPOSURE TO ESLICARBAZEPINE ACETATE BIA 2-093 ON BRAIN DEVELOPMENT AND NEURONAL DIFFERENTIATION/SURVIVAL
dc.relationREGULATION OF NEUROGENESIS BY CALPAINS: RELEVANCE FOR POST-INJURY BRAIN REPAIR
dc.rights.urihttp://creativecommons.org/licenses/by/4.0
dc.subjectNeural stem-cells
dc.subjectFocal cerebral-ischemia
dc.subjectTransient forebrain ischemia
dc.subjectEpidermal-growth-factor
dc.subjectSubventricular zone
dc.subjectBrain-injury
dc.subjectAged rats
dc.subjectHippocampal neurogenesis
dc.subjectBehavioral deficits
dc.subjectGlobal-ischemia
dc.titleInvolvement of calpains in adult neurogenesis: implications for stroke
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitlePHYSIOLOGICAL ROLE OF CALPAINS: HOW DO CALPAINS REGULATE CELL PROLIFERATION AND MIGRATION IN THE BRAIN
oaire.awardTitleEFFECTS OF THE PRENATAL/POSTNATAL EXPOSURE TO ESLICARBAZEPINE ACETATE BIA 2-093 ON BRAIN DEVELOPMENT AND NEURONAL DIFFERENTIATION/SURVIVAL
oaire.awardTitleREGULATION OF NEUROGENESIS BY CALPAINS: RELEVANCE FOR POST-INJURY BRAIN REPAIR
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876-PPCDTI/PTDC%2FSAU-NMC%2F112183%2F2009/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBPD%2F78901%2F2011/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F38127%2F2007/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F78050%2F2011/PT
oaire.citation.startPage22
oaire.citation.titleFrontiers in Cellular Neuroscience
oaire.citation.volume9
oaire.fundingStream5876-PPCDTI
person.familyNameMachado
person.familyNamePombinho de Araújo
person.givenNameVanessa
person.givenNameInês Maria
person.identifierF-4703-2012
person.identifier.ciencia-idF61F-653C-6FBE
person.identifier.ciencia-idD11F-D4CA-2947
person.identifier.orcid0000-0002-6532-7050
person.identifier.orcid0000-0002-2438-0111
person.identifier.scopus-author-id56271084100
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccess
rcaap.typearticle
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