Exercise Improved the Anti-Epileptic Effect of Carbamazepine through GABA Enhancement in Epileptic Rats.

Carbamazepine (CBZ) is an anticonvulsant drug that usually is used for the treatment of seizures. The anti-epileptic and the anti-epileptogenic effect of exercise has been reported, as well. This study was aimed to evaluate the synergic effect of combined therapy of exercise and CBZ in epileptic rats, as well as the alternation of the GABA pathway as a possible involved mechanism. The seizure was induced by pentylenetetrazol (PTZ) injection. Animals were divided into sham, seizure, exercise (EX), CBZ (25, 50 and 75), EX + CBZ (25, 50 and 75). Treadmill forced running for 30 min has been considered as the exercise 5 days per week for four weeks. CBZ was injected in doses of 25, 50 and 75 mg/kg, half an hour before seizure induction and 5 h after doing exercise in the animals forced to exercise. Seizure severity reduced and latency increased in the EX + CBZ (25) and EX + CBZ (50) groups compared to the seizure group. The distribution of GAD65 in both hippocampal CA1 and CA3 areas increased in the EX + CBZ (75) group. GABAA receptor α1 was up-regulated in the CA3 area of the EX + CBZ (75) group. The distribution of GAD65 in the cortical area increased in EX, EX + CBZ (50), CBZ (75) and EX + CBZ (75) groups. GABAA receptor α1 was up-regulated in the neocortex of EX + CBZ (50), CBZ (75) and EX + CBZ (75) groups. Our findings suggested that exercise has improved the efficacy of CBZ and reduced the anti-epileptic dose. The enhancement of GABA signaling might be involved in the synergistic effect of exercise and CBZ.

The effect of exercise on GABA signaling pathway in the model of chemically induced seizures.

AIMS: Gamma amino butyric acid (GABA) imbalance plays a critical role in most neurological disorders including epilepsy. This study assessed the involvement of mild exercise on GABA imbalance following by seizure induction in rats. MAIN METHODS: Seizure was induced by pentylentetrazole (PTZ) injection. Animals were divided into sham, seizure, exercise (EX), co-seizure-induced exercise (Co-SI EX) and Pre-SI EX groups. In the Co-SI EX group, doing exercise and seizure induction was carried out during four weeks. Animals in the Pre-SI EX group exercised in week 1 to week 8 and seizures were induced in week 5 to week 8. Seizure properties, neural viability and expressions of glutamic acid decarboxylase 65 (GAD65) and GABAA receptor α1 in the hippocampus were assessed. KEY FINDINGS: Seizure severity reduced and latency increased in the Co-SI EX and Pre-SI EX groups compared to seizure group. The mean number of dark neurons decreased in all exercise groups compared to seizure group in both CA1 and CA3 areas. The gene level of GAD65 and GABAA receptor α1 was highly expressed in the Co-SI EX group in the hippocampal area. Distribution of GAD65 in the both CA1 and CA3 areas increased in the EX and Co-SI EX groups. GABAA receptor α1 was up-regulated in the CA3 area of Co-SI EX group and down-regulated in the CA1 and CA3 areas of Pre-SI EX group. SIGNIFICANCE: These findings suggest that exercise develop anti-epileptic as well as neuroprotective effects by modulating of GABA disinhibition.