当前位置: X-MOL 学术Neurochem. Int. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Amelioration of diabetes-induced cognitive impairment by Transient Receptor Potential Vanilloid 2 (TRPV2) channel inhibitor: Behavioral and mechanistic study.
Neurochemistry international ( IF 4.4 ) Pub Date : 2020-07-08 , DOI: 10.1016/j.neuint.2020.104783
P Thapak 1 , M Bishnoi 2 , S S Sharma 1
Affiliation  

Transient receptor potential (TRP) channels are Ca2+ permeable non-selective cation channels which play a pivotal role in diabetes and diabetic complications. Among diabetic complications, diabetes-induced cognitive impairment is a major CNS complication. The role of several TRP channels has been investigated extensively for their diverse Ca2+ regulating mechanism, and recently their role has been postulated in the progression of neurodegenerative disorders. However, the role of TRPV2 has not been investigated yet. Therefore, in the present study, the involvement of TRPV2 channels was investigated in diabetes-induced cognitive impairment using TRPV2 inhibitor, tranilast. High glucose exposure in rat C6 glial cells enhances the Ca2+-entry through TRPV2 channels. In our in-vivo study, diabetic rats showed increased gene and protein expression of TRPV2 in the hippocampus. Subsequent increase in the acetylcholinesterase activity in the cortex, as well as decrease in the phosphorylation of Ca2+/calmodulin-dependent protein kinase II (p-CaMKII-Thr-286), p-GSK-3β (Ser-9), p-CREB (Ser-133) and postsynaptic density protein 95 (PSD-95) in the hippocampus were also observed this led to the impairment in the learning and memory as evident from behavioral parameters such as Morris water maze test, passive avoidance and Y-maze test paradigm. Three-week treatment with tranilast (30 and 100 mg/kg, p.o.) showed improvement in learning and memory associated behaviours (Morris water maze test, passive avoidance, and Y-maze test) by increasing the p-CaMKII (Thr-286), p-GSK-3β (Ser-9), p-CREB (Ser-133) and PSD-95 in the hippocampus. Cortical acetylcholinesterase activity was also reduced by the tranilast. These findings depicted that TRPV2 inhibition may be an effective treatment strategy in diabetes-induced cognitive deficits.



中文翻译:

通过瞬时受体电位香草素 2 (TRPV2) 通道抑制剂改善糖尿病引起的认知障碍:行为和机制研究。

瞬时受体电位 (TRP) 通道是 Ca 2+可渗透的非选择性阳离子通道,在糖尿病和糖尿病并发症中起关键作用。在糖尿病并发症中,糖尿病引起的认知障碍是主要的中枢神经系统并发症。几个 TRP 通道的作用因其不同的 Ca 2+调节机制而被广泛研究,最近它们的作用被假定在神经退行性疾病的进展中。然而,尚未研究 TRPV2 的作用。因此,在本研究中,使用 TRPV2 抑制剂曲尼司特研究了 TRPV2 通道在糖尿病诱导的认知障碍中的参与。大鼠 C6 神经胶质细胞中的高葡萄糖暴露增强 Ca 2+- 通过 TRPV2 渠道进入。在我们的体内研究中,糖尿病大鼠的海马中 TRPV2 的基因和蛋白质表达增加。随后皮质中乙酰胆碱酯酶活性增加,以及 Ca 2+磷酸化减少/钙调蛋白依赖性蛋白激酶 II (p-CaMKII-Thr-286)、p-GSK-3β (Ser-9)、p-CREB ​​(Ser-133) 和海马中的突触后密度蛋白 95 (PSD-95)还观察到这会导致学习和记忆受损,这从行为参数中可以明显看出,例如莫里斯水迷宫测试、被动回避和 Y 迷宫测试范式。用曲尼司特(30 和 100 毫克/千克,口服)治疗三周后,通过增加 p-CaMKII (Thr-286) 显示学习和记忆相关行为(莫里斯水迷宫测试、被动回避和 Y 迷宫测试)的改善、p-GSK-3β (Ser-9)、p-CREB ​​(Ser-133) 和 PSD-95 在海马体中。皮质乙酰胆碱酯酶活性也被曲尼司特降低。这些发现表明,抑制 TRPV2 可能是糖尿病引起的认知缺陷的有效治疗策略。

更新日期:2020-07-14
down
wechat
bug