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Calpastatin Overexpression Preserves Cognitive Function Following Seizures, While Maintaining Post-Injury Neurogenesis

2017Journal article Open access
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dc.contributor.authorMachado, Vanessa M.
dc.contributor.authorLourenco, Ana S.
dc.contributor.authorFlorindo, Claudia
dc.contributor.authorFernandes, Raquel
dc.contributor.authorCarvalho, Caetana M.
dc.contributor.authorAraújo, Inês
dc.date.accessioned2018-12-07T14:53:17Z
dc.date.available2018-12-07T14:53:17Z
dc.date.issued2017
dc.description.abstractIn the adult mammalian brain, new neurons continue to be produced throughout life in two main regions in the brain, the subgranular zone (SGZ) in the hippocampus and the subventricular zone in the walls of the lateral ventricles. Neural stem cells (NSCs) proliferate in these niches, and migrate as neuroblasts, to further differentiate in locations where new neurons are needed, either in normal or pathological conditions. However, the endogenous attempt of brain repair is not very efficient. Calpains are proteases known to be involved in neuronal damage and in cell proliferation, migration and differentiation of several cell types, though their effects on neurogenesis are not well known. Previous work by our group has shown that the absence of calpastatin (CAST), the endogenous inhibitor of calpains, impairs early stages of neurogenesis. Since the hippocampus is highly associated with learning and memory, we aimed to evaluate whether calpain inhibition would help improve cognitive recovery after lesion and efficiency of post-injury neurogenesis in this region. For that purpose, we used the kainic acid (KA) model of seizure-induced hippocampal lesion and mice overexpressing CAST. Selected cognitive tests were performed on the 3rd and 8th week after KA-induced lesion, and cell proliferation, migration and differentiation in the dentate gyrus (DG) of the hippocampus of adult mice were analyzed using specific markers. Cognitive recovery was evaluated by testing the animals for recognition, spatial and associative learning and memory. Cognitive function was preserved by CAST overexpression following seizures, while modulation of post-injury neurogenesis was similar to wild type (WT) mice. Calpain inhibition could still be potentially able to prevent the impairment in the formation of new neurons, given that the levels of calpain activity could be reduced under a certain threshold and other harmful effects from the pathological environment could also be controlled.
dc.description.sponsorshipFoundation for Science and Technology (FCT, Portugal); FCT [SFRH/BD/78050/2011, SFRH/BD/79308/2011]; COMPETE; FEDER [PTDC/SAU-NMC/112183/2009, UID/NEU/04539/2013, UID/BIM/04773/2013]
dc.description.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.doi10.3389/fnmol.2017.00060
dc.identifier.issn1662-5099
dc.identifier.urihttp://hdl.handle.net/10400.1/11437
dc.language.isoeng
dc.peerreviewedyes
dc.publisherFrontiers Media Sa
dc.relationREGULATION OF NEUROGENESIS BY CALPAINS: RELEVANCE FOR POST-INJURY BRAIN REPAIR
dc.relationENHANCEMENT OF POST-INJURY NEUROGENESIS BY ANTI-INFLAMMATORY DRUGS AND NITRIC OXIDE
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectTemporal-lobe epilepsy
dc.subjectNeural stem-cells
dc.subjectEctopic granule cells
dc.subjectAdult dentate gyrus
dc.subjectHippocampal neurogenesis
dc.subjectObject recognition
dc.subjectPattern separation
dc.subjectStatus epilepticus
dc.subjectSpatial memory
dc.subjectCalpain
dc.titleCalpastatin Overexpression Preserves Cognitive Function Following Seizures, While Maintaining Post-Injury Neurogenesis
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleREGULATION OF NEUROGENESIS BY CALPAINS: RELEVANCE FOR POST-INJURY BRAIN REPAIR
oaire.awardTitleENHANCEMENT OF POST-INJURY NEUROGENESIS BY ANTI-INFLAMMATORY DRUGS AND NITRIC OXIDE
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F78050%2F2011/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F79308%2F2011/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876-PPCDTI/PTDC%2FSAU-NMC%2F112183%2F2009/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FNEU%2F04539%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FBIM%2F04773%2F2013/PT
oaire.citation.startPage60
oaire.citation.titleFrontiers in Molecular Neuroscience
oaire.citation.volume10
oaire.fundingStream5876-PPCDTI
oaire.fundingStream5876
oaire.fundingStream5876
person.familyNameMachado
person.familyNameLourenço
person.familyNameFlorindo
person.familyNameFernandes
person.familyNamePombinho de Araújo
person.givenNameVanessa
person.givenNameAna Sofia
person.givenNameClaudia
person.givenNameRaquel
person.givenNameInês Maria
person.identifier170713
person.identifierF-4703-2012
person.identifier.ciencia-idF61F-653C-6FBE
person.identifier.ciencia-id7812-FEB4-622A
person.identifier.ciencia-idD11F-D4CA-2947
person.identifier.orcid0000-0002-6532-7050
person.identifier.orcid0000-0003-2882-6026
person.identifier.orcid0000-0003-4549-2179
person.identifier.orcid0000-0002-4181-9800
person.identifier.orcid0000-0002-2438-0111
person.identifier.scopus-author-id56822397300
person.identifier.scopus-author-id26531090300
person.identifier.scopus-author-id56271084100
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
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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
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccess
rcaap.typearticle
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