Publication Database

Seizure-induced cell fate shifts: Tracking neurogenesis in a viral encephalitis-induced epilepsy model (2025)

Art

Poster

Autoren

Weiß, E. (WE 14)

Pauletti, A. (WE 14)

Egilmez, A. (WE 14)

Bröer, S. C. (WE 14)

Kongress

Neuroscience 2025

San Diego, CA, USA, 15. – 19.11.2025

Quelle

Neuroscience 2025 : Abstracts — Society of Neuroscience (Hrsg.)

— S. 16

Sprache

Englisch

Verweise

URL (Volltext): https://www.sfn.org/-/media/SfN/Documents/NEW-SfN/Meetings/Neuroscience-2025/Abstracts-and-Sessions/Abstract-PDFs/SFN25_Abstracts-PDF-Posters_SUN_AM_Final.pdf

Kontakt

Institut für Pharmakologie und Toxikologie

Koserstr. 20
14195 Berlin
+49 30 838 53221
pharmakologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

Neurogenesis, the generation of new neurons, is noted to be disrupted in conventional rodent models of epilepsy, where aberrant maturation and migration of neural stem cells (NSC) contribute to circuit hyperexcitability and cognitive dysfunction. Accelerated proliferation of neural progenitors is described as one main difference after initial insult, which adds to a changed network connectivity. Despite central nervous system (CNS) infections being a leading cause of seizures, the impact of encephalitis-associated seizures on NSC dynamics and differentiation remains largely unexplored. Our research seeks to characterize neurogenesis and define critical therapeutic windows during which modulation of neurogenesis may alter the course of epileptogenesis following CNS infection. By intracortically infecting male C57Bl6/J mice at the age of 7-8 weeks with the Daniel’s strain of Theiler’s Murine Encephalomyelitis Virus, we induced acute seizures in 30-45 % of infected mice. A subset of mice also develops chronic epilepsy several weeks after infection. Mice were sacrificed at 7 (n=28), 14 (n=16), 28 (n=14) and 90 (n=58) days post infection (dpi) to assess neurogenic responses in the subgranular layer of the hippocampal dentate gyrus. A combination of immunohistochemical markers together with in vivo injected BrdU as a proliferation marker were used to follow cell fates. Reactive gliosis, including proliferation of microglia and astrocytes, was elevated in a time-dependent manner post-infection. In contrast, we observed a significant reduction in doublecortin-positive (DCX⁺) immature neurons at 7 and 14 dpi, with more severe depletion in
mice that experienced seizures. Surviving DCX+ cells showed ectopic migration. While neural progenitor proliferation was obliterated in the acute phase (7 dpi) in seizing animals, the number of mature neurons (BrdU+/NeuN+) born during the acute phase was unaffected at 28 dpi. This
could indicate an activated and accelerated proliferation after acute depletion as seen in other models of epilepsy. Ongoing BrdU-based fate mapping at chronic timepoints will determine the long-term development of NSC dynamics. Together, these findings suggest that seizure activity following viral CNS infection significantly alters neurogenic processes, potentially shifting NSC fate and contributing to epileptogenesis.