ORIGINAL RESEARCH article
Front. Mol. Neurosci.
Sec. Brain Disease Mechanisms
Notch Signaling Inhibition Attenuates Epileptogenesis and Hippocampal Damage Without Altering Mossy Fiber Sprouting in Adolescent Rats Post-Status Epilepticus
Ping Yuan
Li Jiang
Li Jiang
Children‘s Hospital of Chongqing Medical University, Chongqing, China
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Abstract
Abstract Background: Notch overactivation and aberrant neurogenesis following status epilepticus (SE) has been identified by our previous study. The current study further supplements this by exploring additional pathological changes during epileptogenesis post-SE, as well as the potential role of Notch in these processes. Notch signaling plays a critical role in neuroregeneration following neurological injuries, including those induced by status epilepticus (SE).This study aimed to investigate the effects of Notch signaling inhibition on epileptogenesis and its underlying mechanisms in the adolescent rat after SE. Methods: Rats were administered N-[N-(3,5-difluorophenacetyl)-L-alanyl)]-S-phenylglycine t-butyl ester (DAPT) immediately after SE induction. Spontaneous recurrent seizures were monitored via electroencephalogram (EEG). Hippocampal synaptic ultrastructure was analyzed using transmission electron microscopy. Nissl staining and Timm staining were performed at 28 days post-SE to evaluate neuronal loss and mossy fiber sprouting (MFS), respectively. Results: EEG recordings demonstrated that DAPT treatment significantly reduced the severity of epileptiform discharges post-SE. Transmission electron microscopy revealed decreased presynaptic active zone length and postsynaptic density thickness in the hippocampal CA1 region of DAPT-treated rats. Nissl staining indicated attenuated hippocampal neuronal lossdegeneration and partial structural restoration following DAPT administration. Notably, Timm staining showed no significant effect of DAPT on MFS compared to controls. Conclusion: Inhibition of Notch signaling alleviates EEG epileptic activity, mitigates synaptic damage, and partially preserves hippocampal neuronal structure in adolescent rats post-SE, without altering MFS. These findings suggest Notch signaling as a potential therapeutic target for post-SE neuroprotection, though its role in MFS remains unclear.
Summary
Keywords
Adolescent rats, DAPT, Epileptogenesis, Notch signaling, Status Epilepticus
Received
10 December 2025
Accepted
09 February 2026
Copyright
© 2026 Yuan, Jiang and Jiang. 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: Ping Yuan
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