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ORIGINAL RESEARCH article

Front. Cell. Neurosci.
Sec. Cellular Neuropathology
Volume 18 - 2024 | doi: 10.3389/fncel.2024.1528918

Viral Encephalitis and Seizures Cause Rapid Depletion of Neuronal Progenitor Cells and Alter Neurogenesis in the Adult Mouse Dentate Gyrus

Provisionally accepted
Alberto Pauletti Alberto Pauletti 1Polina Gurlo Polina Gurlo 1Edna Weiß Edna Weiß 1Ana Beatriz DePaula-Silva Ana Beatriz DePaula-Silva 2Karen S. Wilcox Karen S. Wilcox 2Sonja Bröer Sonja Bröer 1*
  • 1 School of Veterinary Medicine, Freie Universität Berlin, Berlin, Baden-Württemberg, Germany
  • 2 Department of Pharmacology and Toxicology, College of Pharmacy, The University of Utah, Salt Lake City, Utah, United States

The final, formatted version of the article will be published soon.

    Infections impacting the central nervous system 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 towards glial cell fates in infected mice emerges as a possible additional pro-epileptogenic mechanism.

    Keywords: Virus infection, TMEV, seizure, Neurogenesis, progenitor, Cell Proliferation, Epilepsy

    Received: 15 Nov 2024; Accepted: 23 Dec 2024.

    Copyright: © 2024 Pauletti, Gurlo, Weiß, DePaula-Silva, Wilcox and Bröer. 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) or licensor 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.

    * Correspondence: Sonja Bröer, School of Veterinary Medicine, Freie Universität Berlin, Berlin, Baden-Württemberg, Germany

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