在颞叶癫痫的癫痫病灶中，Rev-Erbα 的表达减少，而在匹鲁卡品模型中，Rev-Erbα 的激活具有抗炎和神经保护作用。
Decreased expression of Rev-Erbα in the epileptic foci of temporal lobe epilepsy and activation of Rev-Erbα have anti-inflammatory and neuroprotective effects in the pilocarpine model.
机构信息
Department of Neurosurgery, Xinqiao Hospital, Army Medical University (Third Military Medical University), 183 Xinqiao Main Street, Shapingba District, Chongqing, 400037, China.
Department of Neurosurgery, West China Hospital of Sichuan University, Chengdu, China.
出版信息
J Neuroinflammation. 2020 Jan 31;17(1):43. doi: 10.1186/s12974-020-1718-7.
BACKGROUND
A hallmark of temporal lobe epilepsy (TLE) is brain inflammation accompanied by neuronal demise. Accumulating evidence demonstrates that Rev-Erbα is involved in regulating neuroinflammation and determining the fate of neurons. Therefore, we studied the expression and cellular distribution of Rev-Erbα in the epileptogenic zone of TLE and the effect of treatment with the Rev-Erbα specific agonist SR9009 in the pilocarpine model.
METHODS
The expression pattern of Rev-Erbα was investigated by western blotting, immunohistochemistry, and immunofluorescence labeling in patients with TLE. Next, the effects of SR9009 on neuroinflammation, neuronal apoptosis, and neuronal loss in the mouse hippocampus 7 days after status epilepticus (SE) were assessed by western blotting, immunofluorescence labeling staining, and TUNEL staining.
RESULTS
The western blotting, immunohistochemistry, and immunofluorescence labeling results revealed that Rev-Erbα was downregulated in the epileptogenic zone of TLE patients and mainly localized in neurons, astrocytes, and presumably microglia. Meanwhile, the expression of Rev-Erbα was decreased in the hippocampus and temporal neocortex of mice treated with pilocarpine in the early post-SE and chronic phases. Interestingly, the expression of Rev-Erbα in the normal hippocampus showed a 24-h rhythm; however, the rhythmicity was disturbed in the early phase after SE, and this disturbance was still present in epileptic animals. Our further findings revealed that treatment with SR9009 inhibited NLRP3 inflammasome activation, inflammatory cytokine (IL-1β, IL-18, IL-6, and TNF-α) production, astrocytosis, microgliosis, and neuronal damage in the hippocampus after SE.
CONCLUSIONS
Taken together, these results suggested that a decrease in Rev-Erbα in the epileptogenic zone may contribute to the process of TLE and that the activation of Rev-Erbα may have anti-inflammatory and neuroprotective effects.
背景
颞叶癫痫（TLE）的一个标志是伴有神经元死亡的脑炎症。越来越多的证据表明，Rev-Erbα 参与调节神经炎症，并决定神经元的命运。因此，我们研究了 TLE 致痫区 Rev-Erbα 的表达和细胞分布，以及 Rev-Erbα 特异性激动剂 SR9009 在匹罗卡品模型中的治疗效果。
方法
通过 Western blot、免疫组化和免疫荧光标记研究了 Rev-Erbα 在 TLE 患者中的表达模式。接下来，通过 Western blot、免疫荧光标记染色和 TUNEL 染色评估了 SR9009 对 SE 后 7 天小鼠海马神经炎症、神经元凋亡和神经元丢失的影响。
结果
Western blot、免疫组化和免疫荧光标记结果显示，Rev-Erbα 在 TLE 患者致痫区下调，主要定位于神经元、星形胶质细胞和可能的小胶质细胞。同时，在 SE 后早期和慢性期，用匹罗卡品处理的小鼠海马和颞叶新皮质中 Rev-Erbα 的表达减少。有趣的是，正常海马中的 Rev-Erbα 表达呈 24 小时节律；然而，SE 后早期节律被打乱，这种紊乱在癫痫动物中仍然存在。我们的进一步研究结果表明，SR9009 治疗抑制了 NLRP3 炎性小体激活、炎性细胞因子（IL-1β、IL-18、IL-6 和 TNF-α）产生、星形胶质细胞增生、小胶质细胞增生和 SE 后海马神经元损伤。
结论
综上所述，这些结果表明致痫区 Rev-Erbα 的减少可能导致 TLE 的发生，激活 Rev-Erbα 可能具有抗炎和神经保护作用。
Zotero 插件