Pink1/Parkin signaling mediates pineal mitochondrial autophagy dysfunction and its biological role in a comorbid rat model of depression and insomnia

作者：Zirong Li, Yi Shu, Deguo Liu, Sheng Xie, Liangbo Xian, Jiaqi Keith Luo, Xiuwen Huang, Haixing Jiang · 发表于：Brain Research Bulletin · 年份：2024 · DOI：10.1016/j.brainresbull.2024.111141 · 被引用次数：9 · 研究领域：Autophagy in Disease and Therapy、Sleep and Wakefulness Research、Adipose Tissue and Metabolism

Using a chronic unpredictable mild stress (CUMS) combined with multi-platform water environment sleep deprivation (SD) as an animal model, the occurrence and development of human depression combined with insomnia were simulated. The abnormal mitochondrial autophagy signaling caused by the putative kinase 1/Parkin E3 ubiquitin protein ligase (Pink1/Parkin) signaling pathway directly affects the normal secretion of melatonin by the pineal gland, which may explain the pathogenesis of depression combined with insomnia. This study aims to explore the depression-like behavior, sleep changes, central oxidative stress response, pineal mitochondrial autophagy damage, melatonin secretion, histopathological changes of the pineal gland, and the expression of Pink1/Parkin signaling-related factors in CUMS+SD rats. The results showed that the levels of reactive oxygen species (ROS) in cerebrospinal fluid of CUMS+SD rats significantly increased along with the inflammatory factors Interleukin-1β (IL-1β) and nuclear factor kappa-B (NF-κB) in cerebrospinal fluid. In addition, the number of pineal gland cells significantly decreased, cell boundaries became blurred, cell volume shrank, and apoptotic bodies appeared in the pineal gland tissue under HE staining, indicating pineal gland inflammation. Sleep deprivation further disrupted the levels of autophagy damage factors, including histamine (MDA), glutathione (GSH), and catalase (CAT), in the cerebrospinal fluid of CUMS+ SD rats. Transmission e...