IBRO neuroscience reports · 2026
Moderate-intensity treadmill exercise improved the anticonvulsant efficacy of topiramate and attenuated anxiety and depressive-like side effects in epileptic rats by upregulating 5-HT1A receptors in the hippocampus and cerebral cortex.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Goudarzi Ghazaleh, Aliyari Babak, Soleimani Mansoureh, Vahabzadeh Gelareh, Rasoolijazi Homa, Karimzadeh Fariba
Аннотация
BACKGROUND: Topiramate (TPM) is a broad-spectrum antiseizure medication associated with dose-limited mood-related adverse effects, including depression, which significantly impair patient quality of life and treatment adherence. Although physical exercise confers neuroprotective and mood-stabilizing benefits, its potential to counteract TPM-induced behavioral deficits and the underlying neurobiological mechanisms, particularly within the serotonergic system, remains largely unexplored.
OBJECTIVE: The present study investigated whether exercise reduced the effective dose of topiramate and attenuates its depressive-like side effects in epileptic rats.
METHODS: Male Wistar rats were randomly assigned to nine groups (n = 10/group): Sham, Seizure, Exercise (EX), TPM (25 mg), TPM (50 mg), TPM (70 mg), EX + TPM (25 mg), EX + TPM (50 mg), and EX + TPM (70 mg).The exercise protocol consisted of treadmill running (30 min/day, 5 days/week for 4 weeks). Seizure severity and latency were assessed using the Racine scale. Depressive-like behaviors and anxiety were evaluated by the Tail Suspension Test (TST) and the Elevated Plus Maze (EPM). Immunohistochemistry was performed to quantify 5-HT1A receptor immunoreactive staining intensity in the hippocampal CA1, CA3, and cerebral cortex.
RESULTS: Combination therapy (EX+TPM (50 mg) and EX + TPM (70 mg)) demonstrated superior anticonvulsant effects, significantly reducing seizure scores and prolonging seizure latency compared to TPM monotherapy (p < 0.001). TPM monotherapy dose-dependently exacerbated depressive-like behaviors (e.g., increased immobility in the TPM (70 mg) group, p < 0.001). Crucially, exercise attenuated these adverse effects in all EX + TPM groups. 5-HT1A receptor expression was significantly downregulated in the Seizure and TPM (25 mg) groups compared with the Sham and Exercise groups. In contrast, the EX + TPM (50 mg) and EX + TPM (70 mg) groups showed significant upregulation of 5-HT1A receptors in the hippocampus and cerebral cortex (p < 0.001).
CONCLUSION: The current findings demonstrate that adjunctive moderate-intensity treadmill exercise potentiates the anticonvulsant efficacy of topiramate and effectively counteracts its depressive-like side effects and anxiety. This behavioral improvement was correlated with exercise-mediated upregulation of 5-HT1A receptors, suggesting a potential mechanistic link. These findings provide a preclinical rationale for further investigation into the potential benefits of exercise as an adjunctive therapy in epilepsy, though clinical translation requires additional studies.
OBJECTIVE: The present study investigated whether exercise reduced the effective dose of topiramate and attenuates its depressive-like side effects in epileptic rats.
METHODS: Male Wistar rats were randomly assigned to nine groups (n = 10/group): Sham, Seizure, Exercise (EX), TPM (25 mg), TPM (50 mg), TPM (70 mg), EX + TPM (25 mg), EX + TPM (50 mg), and EX + TPM (70 mg).The exercise protocol consisted of treadmill running (30 min/day, 5 days/week for 4 weeks). Seizure severity and latency were assessed using the Racine scale. Depressive-like behaviors and anxiety were evaluated by the Tail Suspension Test (TST) and the Elevated Plus Maze (EPM). Immunohistochemistry was performed to quantify 5-HT1A receptor immunoreactive staining intensity in the hippocampal CA1, CA3, and cerebral cortex.
RESULTS: Combination therapy (EX+TPM (50 mg) and EX + TPM (70 mg)) demonstrated superior anticonvulsant effects, significantly reducing seizure scores and prolonging seizure latency compared to TPM monotherapy (p < 0.001). TPM monotherapy dose-dependently exacerbated depressive-like behaviors (e.g., increased immobility in the TPM (70 mg) group, p < 0.001). Crucially, exercise attenuated these adverse effects in all EX + TPM groups. 5-HT1A receptor expression was significantly downregulated in the Seizure and TPM (25 mg) groups compared with the Sham and Exercise groups. In contrast, the EX + TPM (50 mg) and EX + TPM (70 mg) groups showed significant upregulation of 5-HT1A receptors in the hippocampus and cerebral cortex (p < 0.001).
CONCLUSION: The current findings demonstrate that adjunctive moderate-intensity treadmill exercise potentiates the anticonvulsant efficacy of topiramate and effectively counteracts its depressive-like side effects and anxiety. This behavioral improvement was correlated with exercise-mediated upregulation of 5-HT1A receptors, suggesting a potential mechanistic link. These findings provide a preclinical rationale for further investigation into the potential benefits of exercise as an adjunctive therapy in epilepsy, though clinical translation requires additional studies.