抑制铁死亡过程可改善海藻酸诱导的大鼠颞叶癫痫中的认知障碍。
Inhibition of ferroptosis processes ameliorates cognitive impairment in kainic acid-induced temporal lobe epilepsy in rats.
作者信息
Ye Qing, Zeng Chunmei, Dong Le, Wu Yuejuan, Huang Qi, Wu Yuan
机构信息
Department of Neurology, The First Affiliated Hospital of Guangxi Medical University 6th Shuangyong Road, Nanning, Guangxi, China.
Department of Neurology, The First Affiliated Hospital of University of South China 69th Chuanshan Road, Hengyang, Hunan, China.
出版信息
Am J Transl Res. 2019 Feb 15;11(2):875-884. eCollection 2019.
Abstract
Hippocampal neuronal death plays a causal role in the cognitive impairment of temporal lobe epilepsy (TLE). Ferroptosis, a novel form of regulated cell death, is strongly linked to cognitive impairment. However, whether ferroptosis is associated with cognitive comorbidities of TLE is unknown. In this study, it was demonstrated that ferroptosis occurs in the hippocampus following kainic acid (KA)-induced TLE in rats. Treatment with ferrostatin-1, a specific inhibitor of ferroptosis, prevented the initiation and progression of ferroptosis in the hippocampus of KA-treated rats. This was through decreased expression of glutathione peroxidase 4, glutathione (GSH) depletion as well as lipid peroxides and iron accumulation. It was also found that ferrostatin-1 prevented hippocampal neuronal loss and rescued cognitive function in KA-induced TLE in rats. These results suggest that ferroptosis is involved in the cognitive impairment of KA-induced TLE in rats, and inhibition of ferroptosis processes ameliorates cognitive impairment in KA-induced TLE in rats.
摘要
海马神经元死亡在颞叶癫痫（TLE）的认知障碍中起因果作用。铁死亡是一种新型的程序性细胞死亡形式，与认知障碍密切相关。然而，铁死亡是否与TLE的认知合并症有关尚不清楚。在本研究中，已证明在大鼠经海藻酸（KA）诱导的TLE后，海马中会发生铁死亡。用铁死亡特异性抑制剂铁抑素-1进行治疗，可防止KA处理大鼠海马中铁死亡的起始和进展。这是通过降低谷胱甘肽过氧化物酶4的表达、消耗谷胱甘肽（GSH）以及减少脂质过氧化物和铁积累来实现的。还发现铁抑素-1可防止KA诱导的TLE大鼠海马神经元丢失并挽救其认知功能。这些结果表明，铁死亡参与了KA诱导的TLE大鼠的认知障碍，抑制铁死亡过程可改善KA诱导的TLE大鼠的认知障碍。
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