Mitochondrial damage in hippocampal neurons of rats with epileptic protein expression of Fas and caspase-3.

Abstract

Epilepsy model in rats was established to observe the behavior and pathological changes, and to detect mitochondrial dysfunction, exploring its possible molecular mechanisms. The epileptic status of Sprague-Dawley (SD) rats was induced by intraperitoneal injection of lithium chloride, and the change of behavior was recorded. Electroencephalogram (EEG) was used to measure the abnormal discharge of neurons in rats. The brain tissue was fixed with polyformaldehyde and the paraffin sections were prepared, and the damage of the hippocampal neurons was observed with Nissl staining. Mitochondrial ATP and mitochondrial DNA were examined to assess mitochondrial dysfunction. Finally, qPCR and western blot analysis were used to detect mRNA and protein expression of fatty acid synthetase (Fas), Fas ligand (FasL) and caspase-3 in rat hippocampal neurons. The correlation between the mitochondrial dysfunction of rat hippocampal neurons and Fas and caspase-3 was analyzed. Compared with the normal group rats, the model group showed typical seizures, which were determined by the Racine attack score. EEG of the hippocampus of the model group was recorded in cluster in model group rats. Nissl staining showed a different degree of damage to the hippocampal neurons in the model group compared with normal rats. The mitochondrial ATP content and DNA content of rat hippocampal neurons in the model group were significantly lower than that of normal rats (P<0.01). The qPCR and western blot results showed that the mRNA and protein expression levels of Fas, FasL and caspase-3 were significantly increased in the hippocampus of rat model group (P<0.01). The expression level of Fas and caspase-3 in hippocampal tissues of rats was negatively correlated with mitochondrial DNA content. In conclusion, seizures cause damage of neuron mitochondria in rat hippocampus leading to death of hippocampal neurons, the mitochondrial damage of hippocampal neurons in epileptic rats was closely related to the expression of Fas and caspase-3.