Alterations of the Hippocampal Neurogenic Niche in a Mouse Model of Dravet Syndrome

Hippocampal neurogenesis, the process by which neural stem cells (NSCs) continuously generate new neurons in the dentate gyrus (DG) of most mammals including humans, is chiefly regulated by neuronal activity. Thus, severe alterations have been found in samples from epilepsy patients and in the hippo...

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Autores: Martín Suárez, Soraya, Abiega Etxabe, Oihane, Ricobaraza, Ana, Hernández Alcoceba, Rubén, Encinas Pérez, Juan Manuel
Formato: artículo
Fecha de publicación:2020
País:España
Recursos:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/49222
Acesso em linha:http://hdl.handle.net/10810/49222
Access Level:acceso abierto
Palavra-chave:neural stem cells
aberrant neurogenesis
gliosis
Dravet syndrome
SCN1A
severe myoclonic epilepsy
dentate granule cells
adult neurogenesis
pattern separation
neurons
gyrus
seizures
differentiation
reorganization
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spelling Alterations of the Hippocampal Neurogenic Niche in a Mouse Model of Dravet SyndromeMartín Suárez, SorayaAbiega Etxabe, OihaneRicobaraza, AnaHernández Alcoceba, RubénEncinas Pérez, Juan Manuelneural stem cellsaberrant neurogenesisgliosisDravet syndromeSCN1Asevere myoclonic epilepsydentate granule cellsadult neurogenesispattern separationneuronsgyrusseizuresdifferentiationreorganizationHippocampal neurogenesis, the process by which neural stem cells (NSCs) continuously generate new neurons in the dentate gyrus (DG) of most mammals including humans, is chiefly regulated by neuronal activity. Thus, severe alterations have been found in samples from epilepsy patients and in the hippocampal neurogenic niche in mouse models of epilepsy. Reactive-like and gliogenic NSCs plus aberrant newborn neurons with altered migration, morphology, and functional properties are induced by seizures in experimental models of temporal lobe epilepsy. Hippocampal neurogenesis participates in memory and learning and in the control of anxiety and stress. It has been therefore hypothesized that part of the cognitive symptoms associated with epilepsy could be promoted by impaired hippocampal neurogenesis. We here analyze for the first time the alterations of the neurogenic niche in a novel mouse model of Dravet syndrome (DS), a genetic encephalopathy with severe epilepsy in infancy and multiple neurological comorbidities. Scn1a(WT/A1783V)mice, hereafter referred to as DS, carrying a heterozygous and clinically relevant SCN1A mutation (A1783V) recapitulate the disease at the genetic and phenotypic levels. We demonstrate that in the neurogenic niche of young adult DS mice there are fewer NSCs, they have impaired cell division and bear reactive-like morphology. In addition, there is significant aberrant neurogenesis. Newborn immature neurons migrate abnormally, and several morphological features are drastically changed. Thus, this study shows for the first time important modifications in hippocampal neurogenesis in DS and opens venues for further research on this topic.This work was supported by Spanish Ministry of Economy and Competitiveness (MINECO) Grant/Award Numbers SAF-2015-70866-R (with FEDER Funds) and RyC-212-11137 to JE and RTI2018-097730-B-I00/MCI/AEI/FEDER, UE, and AC17/00029 (ISCIII)/FEDER to RH-A. SM-S received a Fundacion Tatiana predoctoral fellowship. OA is the recipient of a Basque Government postdoctoral fellowship.Frontiers Media202020202020info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10810/49222reponame:Addi. Archivo Digital para la Docencia y la Investigacióninstname:Universidad del País VascoInglésinfo:eu-repo/grantAgreement/MINECO/SAF-2015-70866-R/info:eu-repo/grantAgreement/MINECO/RyC-212-11137/info:eu-repo/grantAgreement/MINECO/RTI2018-097730-B-I00/https://www.frontiersin.org/articles/10.3389/fcell.2020.00654/fullinfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/3.0/es/2020 Martín-Suárez, Abiega, Ricobaraza, Hernandez-Alcoceba and Encinas. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Atribución 3.0 Españaoai:addi.ehu.eus:10810/492222026-06-18T09:23:17Z
dc.title.none.fl_str_mv Alterations of the Hippocampal Neurogenic Niche in a Mouse Model of Dravet Syndrome
title Alterations of the Hippocampal Neurogenic Niche in a Mouse Model of Dravet Syndrome
spellingShingle Alterations of the Hippocampal Neurogenic Niche in a Mouse Model of Dravet Syndrome
Martín Suárez, Soraya
neural stem cells
aberrant neurogenesis
gliosis
Dravet syndrome
SCN1A
severe myoclonic epilepsy
dentate granule cells
adult neurogenesis
pattern separation
neurons
gyrus
seizures
differentiation
reorganization
title_short Alterations of the Hippocampal Neurogenic Niche in a Mouse Model of Dravet Syndrome
title_full Alterations of the Hippocampal Neurogenic Niche in a Mouse Model of Dravet Syndrome
title_fullStr Alterations of the Hippocampal Neurogenic Niche in a Mouse Model of Dravet Syndrome
title_full_unstemmed Alterations of the Hippocampal Neurogenic Niche in a Mouse Model of Dravet Syndrome
title_sort Alterations of the Hippocampal Neurogenic Niche in a Mouse Model of Dravet Syndrome
dc.creator.none.fl_str_mv Martín Suárez, Soraya
Abiega Etxabe, Oihane
Ricobaraza, Ana
Hernández Alcoceba, Rubén
Encinas Pérez, Juan Manuel
author Martín Suárez, Soraya
author_facet Martín Suárez, Soraya
Abiega Etxabe, Oihane
Ricobaraza, Ana
Hernández Alcoceba, Rubén
Encinas Pérez, Juan Manuel
author_role author
author2 Abiega Etxabe, Oihane
Ricobaraza, Ana
Hernández Alcoceba, Rubén
Encinas Pérez, Juan Manuel
author2_role author
author
author
author
dc.subject.none.fl_str_mv neural stem cells
aberrant neurogenesis
gliosis
Dravet syndrome
SCN1A
severe myoclonic epilepsy
dentate granule cells
adult neurogenesis
pattern separation
neurons
gyrus
seizures
differentiation
reorganization
topic neural stem cells
aberrant neurogenesis
gliosis
Dravet syndrome
SCN1A
severe myoclonic epilepsy
dentate granule cells
adult neurogenesis
pattern separation
neurons
gyrus
seizures
differentiation
reorganization
description Hippocampal neurogenesis, the process by which neural stem cells (NSCs) continuously generate new neurons in the dentate gyrus (DG) of most mammals including humans, is chiefly regulated by neuronal activity. Thus, severe alterations have been found in samples from epilepsy patients and in the hippocampal neurogenic niche in mouse models of epilepsy. Reactive-like and gliogenic NSCs plus aberrant newborn neurons with altered migration, morphology, and functional properties are induced by seizures in experimental models of temporal lobe epilepsy. Hippocampal neurogenesis participates in memory and learning and in the control of anxiety and stress. It has been therefore hypothesized that part of the cognitive symptoms associated with epilepsy could be promoted by impaired hippocampal neurogenesis. We here analyze for the first time the alterations of the neurogenic niche in a novel mouse model of Dravet syndrome (DS), a genetic encephalopathy with severe epilepsy in infancy and multiple neurological comorbidities. Scn1a(WT/A1783V)mice, hereafter referred to as DS, carrying a heterozygous and clinically relevant SCN1A mutation (A1783V) recapitulate the disease at the genetic and phenotypic levels. We demonstrate that in the neurogenic niche of young adult DS mice there are fewer NSCs, they have impaired cell division and bear reactive-like morphology. In addition, there is significant aberrant neurogenesis. Newborn immature neurons migrate abnormally, and several morphological features are drastically changed. Thus, this study shows for the first time important modifications in hippocampal neurogenesis in DS and opens venues for further research on this topic.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10810/49222
url http://hdl.handle.net/10810/49222
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/grantAgreement/MINECO/SAF-2015-70866-R/
info:eu-repo/grantAgreement/MINECO/RyC-212-11137/
info:eu-repo/grantAgreement/MINECO/RTI2018-097730-B-I00/
https://www.frontiersin.org/articles/10.3389/fcell.2020.00654/full
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/3.0/es/
Atribución 3.0 España
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/3.0/es/
Atribución 3.0 España
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:Addi. Archivo Digital para la Docencia y la Investigación
instname:Universidad del País Vasco
instname_str Universidad del País Vasco
reponame_str Addi. Archivo Digital para la Docencia y la Investigación
collection Addi. Archivo Digital para la Docencia y la Investigación
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.301603

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