Ozkan Ayse, Parlak Hande, Sinen Osman, Bulbul Mehmet, Aydin Aslan Mutay, Agar Aysel
Department of Physiology, Akdeniz University, Faculty of Medicine, Antalya, Turkey.
Department of Physiology, Izmir Bakırçay University, Faculty of Medicine, İzmir, Turkey.
Iran J Basic Med Sci. 2025;28(6):790-798. doi: 10.22038/ijbms.2025.82498.17830.
This study was planned to elucidate the mechanism of the protective effect of adropin in an experimental rat model of Parkinson's Disease (PD).
Three-month-old male Wistar rats were randomly divided into four groups: i) Control, ii) Sham, iii) PD, and iv) PD+Adropin. The performance tests were performed seven days after the 6-Hydroxydopamine hydrochloride (6-OHDA) injection into the striatum. The immunoreactivities for tyrosine hydroxylase (TH), G protein-coupled receptor 19 (GPR19), and vascular endothelial growth factor receptor 2 (VEGFR2) were detected by immunohistochemistry (IHC) in the substantia nigra (SN). Dopamine levels were measured by mass spectrometry. Glycogen synthase kinase 3β (GSK3β) and pGSK3β (Ser9) protein levels were evaluated by western blot analysis.
Our study demonstrated that motor performances were significantly improved by adropin treatment. Central adropin injection prevented the loss of nigral dopaminergic neurons and induced VEGFR2 expression but not GPR19 compared to the PD group. The ratio of p-GSK3β/GSK3β did not differ between groups. However, the level of dopamine in SN was increased with adropin injection in the PD+Adropin group.
Our findings reveal that adropin administration has a protective effect on nigral dopaminergic neurons and acts through the VEGFR2 signaling pathway.
本研究旨在阐明阿德罗宁在帕金森病（PD）实验大鼠模型中的保护作用机制。
将3个月大的雄性Wistar大鼠随机分为四组：i）对照组，ii）假手术组，iii）帕金森病组，iv）帕金森病+阿德罗宁组。在向纹状体注射盐酸6-羟基多巴胺（6-OHDA）7天后进行行为测试。通过免疫组织化学（IHC）检测黑质（SN）中酪氨酸羟化酶（TH）、G蛋白偶联受体19（GPR19）和血管内皮生长因子受体2（VEGFR2）的免疫反应性。通过质谱法测量多巴胺水平。通过蛋白质印迹分析评估糖原合酶激酶3β（GSK3β）和磷酸化GSK3β（Ser⁹）的蛋白水平。
我们的研究表明，阿德罗宁治疗可显著改善运动行为。与帕金森病组相比，中枢注射阿德罗宁可防止黑质多巴胺能神经元丢失并诱导VEGFR2表达，但不诱导GPR19表达。各组之间p-GSK3β/GSK3β的比值无差异。然而，帕金森病+阿德罗宁组注射阿德罗宁后黑质中的多巴胺水平升高。
我们的研究结果表明，给予阿德罗宁对黑质多巴胺能神经元具有保护作用，并通过VEGFR2信号通路发挥作用。
