Viral encephalitis and seizures cause rapid depletion of neuronal progenitor cells and alter neurogenesis in the adult mouse dentate gyrus

Infections impacting the central nervous system (CNS) constitute a substantial predisposing factor for the emergence of epileptic seizures. Given that epilepsy conventionally correlates with hippocampal sclerosis and neuronal degeneration, a potentially innovative avenue for therapeutic intervention...

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Main Authors: Alberto Pauletti, Polina Gurlo, Edna Weiß, Ana Beatriz DePaula-Silva, Karen S. Wilcox, Sonja Bröer
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Cellular Neuroscience
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Online Access:https://www.frontiersin.org/articles/10.3389/fncel.2024.1528918/full
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author Alberto Pauletti
Polina Gurlo
Edna Weiß
Ana Beatriz DePaula-Silva
Karen S. Wilcox
Sonja Bröer
author_facet Alberto Pauletti
Polina Gurlo
Edna Weiß
Ana Beatriz DePaula-Silva
Karen S. Wilcox
Sonja Bröer
author_sort Alberto Pauletti
collection DOAJ
description Infections impacting the central nervous system (CNS) constitute a substantial predisposing factor for the emergence of epileptic seizures. Given that epilepsy conventionally correlates with hippocampal sclerosis and neuronal degeneration, a potentially innovative avenue for therapeutic intervention involves fostering adult neurogenesis, a process primarily occurring within the subgranular zone of the dentate gyrus (DG) through the differentiation of neural stem cells (NSC). While experimental seizures induced by chemoconvulsants or electrical stimulation transiently enhance neurogenesis, the effects of encephalitis and the resultant virus-induced seizures remain inadequately understood. Thus, this study employed the Theiler's Murine Encephalomyelitis Virus (TMEV) model of virus-induced seizures in adult C57BL/6J mice to investigate the impact of infection-induced seizures on neurogenesis at three distinct time points [3, 7, and 14 days post-infection (dpi)]. Immunohistochemical analysis revealed a reduction in the overall number of proliferating cells post-infection. More notably, the specific cell types exhibiting proliferation diverged between TMEV and control (CTR) mice: (1) Neuronal progenitors (doublecortin, DCX+) were almost entirely absent at 3 dpi in the dorsal DG. They resumed proliferation at 14 dpi, but, did not recover to CTR levels, and displayed aberrant migration patterns. (2) The number of proliferating NSCs significantly decreased within the dorsal DG of TMEV mice at 14 dpi compared to CTR, while (3) a heightened population of proliferating astrocytes was observed. Most observed changes were not different between seizing and non-seizing infected mice. In summary, our findings demonstrate that viral infection rapidly depletes neuronal progenitor cells and causes aberrant migration of the remaining ones, potentially contributing to hyperexcitability. Additionally, the increased differentiation toward glial cell fates in infected mice emerges as a possible additional pro-epileptogenic mechanism.
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spelling doaj-art-8dcf560afdfe48efa3d72b871442b8ae2025-01-14T06:10:32ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022025-01-011810.3389/fncel.2024.15289181528918Viral encephalitis and seizures cause rapid depletion of neuronal progenitor cells and alter neurogenesis in the adult mouse dentate gyrusAlberto Pauletti0Polina Gurlo1Edna Weiß2Ana Beatriz DePaula-Silva3Karen S. Wilcox4Sonja Bröer5School of Veterinary Medicine, Institute of Pharmacology and Toxicology, Freie Universität Berlin, Berlin, GermanySchool of Veterinary Medicine, Institute of Pharmacology and Toxicology, Freie Universität Berlin, Berlin, GermanySchool of Veterinary Medicine, Institute of Pharmacology and Toxicology, Freie Universität Berlin, Berlin, GermanyDepartment of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT, United StatesDepartment of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT, United StatesSchool of Veterinary Medicine, Institute of Pharmacology and Toxicology, Freie Universität Berlin, Berlin, GermanyInfections impacting the central nervous system (CNS) constitute a substantial predisposing factor for the emergence of epileptic seizures. Given that epilepsy conventionally correlates with hippocampal sclerosis and neuronal degeneration, a potentially innovative avenue for therapeutic intervention involves fostering adult neurogenesis, a process primarily occurring within the subgranular zone of the dentate gyrus (DG) through the differentiation of neural stem cells (NSC). While experimental seizures induced by chemoconvulsants or electrical stimulation transiently enhance neurogenesis, the effects of encephalitis and the resultant virus-induced seizures remain inadequately understood. Thus, this study employed the Theiler's Murine Encephalomyelitis Virus (TMEV) model of virus-induced seizures in adult C57BL/6J mice to investigate the impact of infection-induced seizures on neurogenesis at three distinct time points [3, 7, and 14 days post-infection (dpi)]. Immunohistochemical analysis revealed a reduction in the overall number of proliferating cells post-infection. More notably, the specific cell types exhibiting proliferation diverged between TMEV and control (CTR) mice: (1) Neuronal progenitors (doublecortin, DCX+) were almost entirely absent at 3 dpi in the dorsal DG. They resumed proliferation at 14 dpi, but, did not recover to CTR levels, and displayed aberrant migration patterns. (2) The number of proliferating NSCs significantly decreased within the dorsal DG of TMEV mice at 14 dpi compared to CTR, while (3) a heightened population of proliferating astrocytes was observed. Most observed changes were not different between seizing and non-seizing infected mice. In summary, our findings demonstrate that viral infection rapidly depletes neuronal progenitor cells and causes aberrant migration of the remaining ones, potentially contributing to hyperexcitability. Additionally, the increased differentiation toward glial cell fates in infected mice emerges as a possible additional pro-epileptogenic mechanism.https://www.frontiersin.org/articles/10.3389/fncel.2024.1528918/fullvirus infectionTMEVseizureneurogenesisprogenitorcell proliferation
spellingShingle Alberto Pauletti
Polina Gurlo
Edna Weiß
Ana Beatriz DePaula-Silva
Karen S. Wilcox
Sonja Bröer
Viral encephalitis and seizures cause rapid depletion of neuronal progenitor cells and alter neurogenesis in the adult mouse dentate gyrus
Frontiers in Cellular Neuroscience
virus infection
TMEV
seizure
neurogenesis
progenitor
cell proliferation
title Viral encephalitis and seizures cause rapid depletion of neuronal progenitor cells and alter neurogenesis in the adult mouse dentate gyrus
title_full Viral encephalitis and seizures cause rapid depletion of neuronal progenitor cells and alter neurogenesis in the adult mouse dentate gyrus
title_fullStr Viral encephalitis and seizures cause rapid depletion of neuronal progenitor cells and alter neurogenesis in the adult mouse dentate gyrus
title_full_unstemmed Viral encephalitis and seizures cause rapid depletion of neuronal progenitor cells and alter neurogenesis in the adult mouse dentate gyrus
title_short Viral encephalitis and seizures cause rapid depletion of neuronal progenitor cells and alter neurogenesis in the adult mouse dentate gyrus
title_sort viral encephalitis and seizures cause rapid depletion of neuronal progenitor cells and alter neurogenesis in the adult mouse dentate gyrus
topic virus infection
TMEV
seizure
neurogenesis
progenitor
cell proliferation
url https://www.frontiersin.org/articles/10.3389/fncel.2024.1528918/full
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