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运动对化学诱导性癫痫模型中 GABA 信号通路的影响。

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

机构信息

Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran; Department of Anatomy, Iran University of Medical Sciences, Tehran, Iran.

Department of Anatomy, Arak University of Medical Sciences, Arak, Iran.

出版信息

Life Sci. 2019 Sep 1;232:116667. doi: 10.1016/j.lfs.2019.116667. Epub 2019 Jul 18.

Abstract

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 GABA 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 GABA 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. GABA 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.

摘要

目的

γ-氨基丁酸(GABA)失衡在包括癫痫在内的大多数神经疾病中起着关键作用。本研究评估了轻度运动对戊四氮(PTZ)诱导癫痫发作后 GABA 失衡的影响。

方法

通过戊四氮(PTZ)注射诱导癫痫。动物分为假手术、癫痫、运动(EX)、共癫痫诱导运动(Co-SI EX)和预癫痫诱导运动(Pre-SI EX)组。在 Co-SI EX 组中,在四周内进行运动和癫痫诱导。Pre-SI EX 组的动物在第 1 周到第 8 周进行运动,在第 5 周到第 8 周进行癫痫诱导。评估了癫痫发作特性、神经活力以及海马中谷氨酸脱羧酶 65(GAD65)和 GABA 受体α1 的表达。

结果

与癫痫组相比,Co-SI EX 和 Pre-SI EX 组的癫痫严重程度降低,潜伏期延长。与癫痫组相比,所有运动组的 CA1 和 CA3 区的暗神经元数量均减少。在海马区,Co-SI EX 组的 GAD65 和 GABA 受体α1 的基因水平高度表达。在 EX 和 Co-SI EX 组中,GAD65 在 CA1 和 CA3 区的分布增加。Co-SI EX 组的 CA3 区 GABA 受体α1 上调,Pre-SI EX 组的 CA1 和 CA3 区下调。

结论

这些发现表明,运动通过调节 GABA 抑制来发挥抗癫痫和神经保护作用。

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