Department of Neurology, Affiliated Hospital of Qingdao University, Qingdao, China.
Department of Neurology, Affiliated Hospital of Qingdao University, Qingdao, China.
Life Sci. 2020 Oct 15;259:118159. doi: 10.1016/j.lfs.2020.118159. Epub 2020 Aug 4.
Parkinson's disease dementia (PDD) is one of the most common non-motor symptoms of advanced Parkinson's disease (PD). This study aimed to determine whether intranasal insulin has protective effects on cognition in the rat PD model induced by 6-hydroxylase dopamine (6-OHDA) through the insulin signaling pathway.
The rats were given intranasal insulin administration for six weeks after unilateral medial forebrain bundle (MFB) injection of 6-OHDA. Then a series of cognitive-behavioral tests, immunofluorescence, and immunoblotting was performed on the rats.
The results demonstrated that the injection of 6-OHDA in the unilateral MFB damaged working memory and long-term habituation of rats in the T-maze rewarded alternation test and hole-board test. Besides, rats with unilateral 6-OHDA injury performed poorly in terms of escape latency and average speed during the hidden platform training phase rather than in the probe trial of the Morris Water Maze (MWM) test. Immunofluorescence results showed that unilateral 6-OHDA injury in MFB led to the massive death of ipsilateral-substantia nigra (SN) tyrosine hydroxylase (TH)-positive neurons. Western blot results further indicated that 6-OHDA-induced necrosis of ipsilateral-SN dopaminergic neurons reduced the levels of p-Akt (Ser473) and p-GSK3β (Ser9) in the ipsilateral-hippocampus.
These findings provide a solid evidence base for the relationship between PD cognitive impairment and insulin signaling pathways.
帕金森病痴呆（PDD）是晚期帕金森病（PD）最常见的非运动症状之一。本研究旨在通过胰岛素信号通路确定经鼻内给予胰岛素是否对 6-羟多巴胺（6-OHDA）诱导的大鼠 PD 模型的认知具有保护作用。
在单侧中脑束（MFB）注射 6-OHDA 后，大鼠接受了六周的经鼻内胰岛素给药。然后对大鼠进行了一系列认知行为测试、免疫荧光和免疫印迹。
结果表明，单侧 MFB 中的 6-OHDA 注射损伤了大鼠在 T 迷宫奖励交替测试和洞板测试中的工作记忆和长期习惯化。此外，单侧 6-OHDA 损伤的大鼠在隐藏平台训练阶段的逃避潜伏期和平均速度方面表现不佳，而在 Morris 水迷宫（MWM）测试的探针试验中表现不佳。免疫荧光结果显示，MFB 中的单侧 6-OHDA 损伤导致同侧黑质（SN）酪氨酸羟化酶（TH）阳性神经元大量死亡。Western blot 结果进一步表明，6-OHDA 诱导的同侧 SN 多巴胺能神经元坏死降低了同侧海马中 p-Akt（Ser473）和 p-GSK3β（Ser9）的水平。
这些发现为 PD 认知障碍与胰岛素信号通路之间的关系提供了坚实的证据基础。
