Medical Physiology Department, Faculty of Medicine, Menoufia University, Menoufia, 32511, Egypt.
Medical Physiology Department, Menoufia National University, Menoufia, Egypt.
Neurochem Res. 2024 Nov 22;50(1):30. doi: 10.1007/s11064-024-04282-x.
Exposure to rotenone results in similar pathophysiological features as Parkinson's disease. Inflammation and oxidative stress are essential to PD pathogenesis. Maresin-1 has potent anti-inflammatory properties and promotes the regression of inflammation function. The current study aimed to evaluate the protective effects of Maresin-1 (MaR1) in rotenone (ROT)-induced PD and whether this protective role is associated with the initiation of the Janus kinase (JAK)-signal transducers and activator of transcription (STAT) signaling pathway. Thirty male Wister rats were classified into control, ROT-treated, and ROT + MaR1-treated groups. Rats underwent rotarod, open field, grip strength, and stepping tests as part of their motor behavioral evaluation. Serum glial cell-derived neurotrophic factor (GDNF) and striatal dopamine, acetylcholine, malondialdehyde (MDA), reduced glutathione (GSH), TNF-α, IL-6, and IL-1β were evaluated. Expression of JAK1 and STAT3 genes was assessed in striatum. Then, the tissue was subjected to histological and immunohistochemical evaluation for caspase-3, GFAP, and NF-kB. The administrated group with rotenone showed significant motor behavioral impairment. This was accompanied by reduced levels of GDNF and dopamine and increased levels of acetylcholine, as well as augmented oxidative stress and inflammatory biomarkers and reduced antioxidant activity. Inflammatory pathways (JAK1/STAT3, caspase-3, and NF-kB) were upregulated. Histopathological changes and upregulation in GFAP immunopositive reaction were observed. Remarkably, MaR1 treatment effectively alleviated behavior, histopathological changes, and biochemical alterations induced by ROT. MaR1 exerts protective effects against ROT-induced PD by its anti-inflammatory, antiapoptotic, and antioxidant properties. MaR1 mechanisms of action may involve modulation of pathways such as JAK/STAT.
鱼藤酮暴露会导致与帕金森病相似的病理生理特征。炎症和氧化应激是 PD 发病机制的关键。maresin-1 具有强大的抗炎特性，并促进炎症功能的消退。本研究旨在评估maresin-1（MaR1）在鱼藤酮（ROT）诱导的 PD 中的保护作用，以及这种保护作用是否与 Janus 激酶（JAK）-信号转导和转录激活因子（STAT）信号通路的启动有关。30 只雄性 Wister 大鼠被分为对照组、ROT 处理组和 ROT+MaR1 处理组。大鼠进行了旋转棒、旷场、握力和步态测试，作为其运动行为评估的一部分。评估血清神经胶质细胞源性神经营养因子（GDNF）和纹状体多巴胺、乙酰胆碱、丙二醛（MDA）、还原型谷胱甘肽（GSH）、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-1β（IL-1β）。评估纹状体中 JAK1 和 STAT3 基因的表达。然后，对组织进行 caspase-3、GFAP 和 NF-kB 的组织学和免疫组织化学评估。给予鱼藤酮的实验组表现出明显的运动行为障碍。这伴随着 GDNF 和多巴胺水平降低，乙酰胆碱水平升高，以及氧化应激和炎症生物标志物增加，抗氧化活性降低。炎症途径（JAK1/STAT3、caspase-3 和 NF-kB）上调。观察到组织病理学变化和 GFAP 免疫阳性反应的上调。值得注意的是，MaR1 治疗可有效缓解 ROT 诱导的 PD 引起的行为、组织病理学变化和生化改变。MaR1 通过其抗炎、抗凋亡和抗氧化特性对 ROT 诱导的 PD 发挥保护作用。MaR1 的作用机制可能涉及调节 JAK/STAT 等途径。
