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

Frontiers in Cell and Developmental Biology

Ana Ricobaraza²  Rubén Hernandez-Alcoceba²  Juan Manuel Encinas³  Soraya Martín-Suárez⁴  Oihane Abiega⁴ 

[1] Department of Neurosciences, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Spain;Gene Therapy Program CIMA, IdiSNA, Navarra Institute for Health Research, University of Navarra, Pamplona, Spain;IKERBASQUE, The Basque Foundation for Science, Bilbao, Spain;The Neural Stem Cell and Neurogenesis Laboratory, Achucarro Basque Center for Neuroscience, Leioa, Spain;

关键词: neural stem cells;    aberrant neurogenesis;    gliosis;    Dravet syndrome;    SCN1A;   

DOI  :  10.3389/fcell.2020.00654

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown