Investigating the Effect of Eight Weeks of Moderate-Intensity Continuous Training on the Expression of GABA, GAD65, GAD67, and GAT3 Proteins in the Hippocampus of Rats with Epilepsy

Abstract

Introduction: The impairment of the GABAergic system plays an important role in increasing the excitability of hippocampal networks and the persistence of seizures in epilepsy. The present study aimed to investigate the effects of eight weeks of moderate-intensity continuous training (MICT) on the expression of GABA, GAD65, GAD67, and GAT3 proteins in the hippocampus of epileptic rats. Methods: In this study, 32 male Wistar rats, aged 6–8 weeks, were randomly assigned to four groups: control, sham, epilepsy, and epilepsy+ MICT. Epilepsy was induced via intrahippocampal injection of kainic acid and confirmed using the Racine scale. The epilepsy+ MICT group performed an eight-week exercise intervention consisting of five sessions per week; each session lasted 45 minutes, with 40 minutes of running at 60% Vmax. Forty-eight hours after completion of the protocol, the hippocampus was extracted, and protein expression was measured using western blotting. Data analysis was performed using one-way ANOVA and Tukey's post hoc test at a significance level of 0.05 with SPSS software. Results: Epilepsy induction significantly decreased the expression levels of GABA, GAD65, and GAD67 compared with the control group (P<0.0001). In the epilepsy+ MICT group, GAD67 expression significantly increased and differed significantly from that in the epilepsy group (P<0.0001), whereas the changes in GABA and GAD65 levels were not found to be statistically significant compared with the epilepsy group. Moreover, GAT3 expression was significantly higher in the epilepsy group than in the other groups, and the MICT intervention significantly reduced its expression (P<0.0001). Seizure severity was also significantly lower in the MICT group than in the epilepsy group. Conclusion: Moderate-intensity continuous training may help reduce seizure severity in epileptic rats and partially attenuate hippocampal inhibitory-system dysfunction by increasing GAD67 and decreasing GAT3.