ORIGINAL RESEARCH article
Front. Neurosci.
Sec. Neurodevelopment
Volume 19 - 2025 | doi: 10.3389/fnins.2025.1626118
This article is part of the Research TopicTherapeutic Potential of Adult Neurogenesis in Neurodegenerative and Neuropsychiatric DisordersView all 6 articles
Inhibiting aberrant seizure-induced neurogenesis by temozolomide improves cognitive impairments associated with long-term amygdala kindling
Provisionally accepted
- Trent University, Peterborough, Canada
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In the adult dentate gyrus, new neurons are continuously generated and integrated into the existing circuitry where they play a crucial role in maintaining important functions related to learning and memory. Seizures not only robustly increase levels of hippocampal neurogenesis but can also induce aberrant migration and functional development of these new neurons, which has been hypothesized to promote network excitability and epileptogenesis. However, the contribution of new neurons to the development of epilepsy-related cognitive impairments remains unclear. Here, we investigated whether suppressing this abnormal elevation in neurogenesis that occur with seizures could prevent the emergence of cognitive dysfunction and behavioural deficits associated with chronic epilepsy.Using the long-term amygdala kindling model (consisting of 99 electrical stimulations), we demonstrate that initiating cyclic treatment with the DNA-alkylating agent temozolomide (TMZ) during a period of heightened neurogenic activity can reduce aberrant hippocampal neurogenesis and rescue impairments in a contextual fear discrimination task known to depend on functional neurogenesis. In addition, TMZ treatment also showed prevented object recognition memory deficits after kindling. Together, our findings suggest kindled seizures trigger the production of new neurons that can effectively rewire and interfere with hippocampal circuit function which can contribute to the development of chronic cognitive and behavioural deficits as seen in both patients with epilepsy and other rodent models. Thus, strategies that can selectively reduce aberrant adult neurogenesis may serve as a novel approach to treat cognitive deficits associated with epilepsy.
Keywords: adult neurogenesis, Pattern Separation, Memory, plasticity, kindling, seizure, Epilepsy, Hippocampus
Received: 10 May 2025; Accepted: 30 Jul 2025.
Copyright: © 2025 Francis, S Reive, Lehmann and Fournier. 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: Neil M Fournier, Trent University, Peterborough, Canada
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