Department of Pathology and Pathophysiology, Faculty of Basic Medical Sciences, Kunming Medical University, 1168 West Chunrong Road, Kunming, 650500, People's Republic of China.
Drug Rehabilitation Center, Huaixian Street, Datong, 038300, Shanxi, People's Republic of China.
Neurochem Res. 2019 Apr;44(4):978-993. doi: 10.1007/s11064-019-02733-4. Epub 2019 Feb 12.
Cognitive impairment in diabetes (CID) is a severe chronic complication of diabetes mellitus (DM). It has been hypothesized that diabetes can lead to cognitive dysfunction due to expression changes of excitatory neurotransmission mediated by N-methyl-D-aspartate receptors (NMDAR) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR); however, the pathogenesis involved in this has not been fully understood, especially at early phase of DM. Here, we sought to determine the cognitive changes and aim to correlate this with the expression changes of NMDAR and AMPAR of glutamate signaling pathways in the rat hippocampus from early phase of DM and in the course of the disease progression. By Western blot analysis and immunofluorescence labeling, the hippocampus in diabetic rats showed a significant increase in protein expression NMDAR subunits NR1, NR2A and NR2B and AMPAR subunit GluR1. Along with this, behavioral test by Morris water maze showed a significant decline in their performance when compared with the control rats. It is suggested that NR1, NR2A, NR2B and GluR1are involved in learning and memory and that their expression alterations maybe correlated with the occurrence and development of CID in diabetic rats induced by streptozotocin.
糖尿病认知障碍(CID)是糖尿病(DM)的一种严重慢性并发症。据推测,糖尿病可能会导致认知功能障碍,这是由于 N-甲基-D-天冬氨酸受体(NMDAR)和α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体(AMPAR)介导的兴奋性神经递质表达变化所致;然而,其发病机制尚未完全阐明,尤其是在 DM 的早期阶段。在这里,我们试图确定认知变化,并旨在将其与糖尿病早期大鼠海马中谷氨酸信号通路的 NMDAR 和 AMPAR 表达变化相关联,以及疾病进展过程中。通过 Western blot 分析和免疫荧光标记,糖尿病大鼠的海马体显示 NMDAR 亚基 NR1、NR2A 和 NR2B 以及 AMPAR 亚基 GluR1 的蛋白表达显著增加。与此相关的是,通过 Morris 水迷宫的行为测试显示,与对照组大鼠相比,它们的表现明显下降。这表明 NR1、NR2A、NR2B 和 GluR1 参与学习和记忆,它们的表达变化可能与链脲佐菌素诱导的糖尿病大鼠 CID 的发生和发展有关。