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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Frontiers Media S.A.
2020-07-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fcell.2020.00654/full |
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| author | Soraya Martín-Suárez Oihane Abiega Ana Ricobaraza Rubén Hernandez-Alcoceba Juan Manuel Encinas Juan Manuel Encinas Juan Manuel Encinas |
| author_facet | Soraya Martín-Suárez Oihane Abiega Ana Ricobaraza Rubén Hernandez-Alcoceba Juan Manuel Encinas Juan Manuel Encinas Juan Manuel Encinas |
| author_sort | Soraya Martín-Suárez |
| collection | DOAJ |
| 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. Scn1aWT/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. |
| first_indexed | 2024-12-21T15:39:58Z |
| format | Article |
| id | doaj.art-cd5b3ba7cb7040268384019b7be7b62e |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-21T15:39:58Z |
| publishDate | 2020-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-cd5b3ba7cb7040268384019b7be7b62e2022-12-21T18:58:32ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2020-07-01810.3389/fcell.2020.00654558826Alterations of the Hippocampal Neurogenic Niche in a Mouse Model of Dravet SyndromeSoraya Martín-Suárez0Oihane Abiega1Ana Ricobaraza2Rubén Hernandez-Alcoceba3Juan Manuel Encinas4Juan Manuel Encinas5Juan Manuel Encinas6The Neural Stem Cell and Neurogenesis Laboratory, Achucarro Basque Center for Neuroscience, Leioa, SpainThe Neural Stem Cell and Neurogenesis Laboratory, Achucarro Basque Center for Neuroscience, Leioa, SpainGene Therapy Program CIMA, IdiSNA, Navarra Institute for Health Research, University of Navarra, Pamplona, SpainGene Therapy Program CIMA, IdiSNA, Navarra Institute for Health Research, University of Navarra, Pamplona, SpainThe Neural Stem Cell and Neurogenesis Laboratory, Achucarro Basque Center for Neuroscience, Leioa, SpainDepartment of Neurosciences, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, SpainIKERBASQUE, The Basque Foundation for Science, Bilbao, SpainHippocampal 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. Scn1aWT/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.https://www.frontiersin.org/article/10.3389/fcell.2020.00654/fullneural stem cellsaberrant neurogenesisgliosisDravet syndromeSCN1A |
| spellingShingle | Soraya Martín-Suárez Oihane Abiega Ana Ricobaraza Rubén Hernandez-Alcoceba Juan Manuel Encinas Juan Manuel Encinas Juan Manuel Encinas Alterations of the Hippocampal Neurogenic Niche in a Mouse Model of Dravet Syndrome Frontiers in Cell and Developmental Biology neural stem cells aberrant neurogenesis gliosis Dravet syndrome SCN1A |
| title | 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_short | 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 |
| topic | neural stem cells aberrant neurogenesis gliosis Dravet syndrome SCN1A |
| url | https://www.frontiersin.org/article/10.3389/fcell.2020.00654/full |
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