Neurology Department, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, No.7 Weiwu Road, Zhengzhou, Henan Province, 450003, China.
J Neuroinflammation. 2024 Oct 10;21(1):259. doi: 10.1186/s12974-024-03251-z.
Melanin concentrating hormone (MCH) controls many brain functions, such as sleep/wake cycle and memory, and modulates the inflammation response. Previous studies have shown that influenza A virus (IAV) infection-induced neuroinflammation leads to central nervous damage. This study investigated the potential effects of MCH against neuroinflammation induced by IAV infection and its mechanism. MCH (1 and 2 mg/ml) was administrated for 5 consecutive days before IAV infection. Pentobarbital-induced sleep tests, an open-field test, and a Morris water maze were performed to measure sleep quality, spatial learning and memory ability. Neuronal loss and microglial activation were observed with Nissl staining and immunofluorescence assay. The levels of inflammatory cytokines and the expression of the JNK/ERK signaling pathway were examined by ELISA and western blot. IAV infection led to poor sleep quality, impaired the ability of spatial learning and memory, caused neuronal loss and microglial activation in mice's hippocampus and cortex. Meanwhile the level of inflammatory cytokines increased, and the JNK/ERK signaling pathway was activated after IAV infection. MCH administration significantly alleviated IAV-induced neuroinflammation, cognitive impairment, and sleep disorder, decreased the levels of inflammatory cytokines, and inhibited neuronal loss and microglial activation in the hippocampus and cortex by regulating the JNK/ERK signaling pathway. Therefore, MCH alleviated the neuroinflammation, spatial learning and memory impairment, and sleep disorder in IAV-infected mice by regulating the JNK/ERK signaling pathway.
黑色素聚集激素（MCH）控制着许多大脑功能，如睡眠/觉醒周期和记忆，并调节炎症反应。先前的研究表明，甲型流感病毒（IAV）感染引起的神经炎症会导致中枢神经系统损伤。本研究探讨了 MCH 对 IAV 感染引起的神经炎症的潜在作用及其机制。在 IAV 感染前连续 5 天给予 MCH（1 和 2 mg/ml）。戊巴比妥诱导的睡眠试验、旷场试验和 Morris 水迷宫用于测量睡眠质量、空间学习和记忆能力。通过尼氏染色和免疫荧光分析观察神经元丢失和小胶质细胞激活。通过 ELISA 和 Western blot 检测炎症细胞因子水平和 JNK/ERK 信号通路的表达。IAV 感染导致睡眠质量下降，空间学习和记忆能力受损，导致小鼠海马体和皮质神经元丢失和小胶质细胞激活。同时，IAV 感染后炎症细胞因子水平升高，JNK/ERK 信号通路被激活。MCH 给药可显著缓解 IAV 诱导的神经炎症、认知障碍和睡眠障碍，降低炎症细胞因子水平，并通过调节 JNK/ERK 信号通路抑制海马体和皮质神经元丢失和小胶质细胞激活。因此，MCH 通过调节 JNK/ERK 信号通路缓解了 IAV 感染小鼠的神经炎症、空间学习和记忆障碍以及睡眠障碍。
