Melatonin alleviates cognition impairment by antagonizing brain insulin resistance in aged rats fed a high-fat diet

文献类型： 外文期刊

第一作者： Xu, Jiqu

作者： Xu, Jiqu;Ma, Congcong;Chen, Meng;Huang, Qingde;Deng, Qianchun;Huang, Fenghong;Xu, Jiqu;Ma, Congcong;Chen, Meng;Huang, Qingde;Deng, Qianchun;Huang, Fenghong;Gao, Hui;Zhang, Li;Rong, Shuang;Yang, Wei

作者机构：

关键词： amyloid-beta; brain insulin resistance; cognition impairment; melatonin; neuroinflammation; oxidative stress; TAU phosphorylation

期刊名称：JOURNAL OF PINEAL RESEARCH （ 影响因子：13.007； 五年影响因子：12.936 ）

ISSN： 0742-3098

年卷期： 2019 年 67 卷 2 期

页码：

收录情况： SCI

摘要： Brain insulin resistance, induced by neuroinflammation and oxidative stress, contributes to neurodegeneration, that is, processes that are associated with A beta accumulation and TAU hyperphosphorylation. Here, we tested the effect of chronic administration of melatonin (MLT) on brain insulin resistance and cognition deficits caused by a high-fat diet (HFD) in aged rats. Results showed that MLT supplementation attenuated peripheral insulin resistance and lowered hippocampal oxidative stress levels. Activated microglia and astrocytes and hippocampal levels of TNF-alpha in HFD-fed rats were reduced by MLT treatment. Melatonin also prevented HFD-induced increases in beta-amyloid (A beta) accumulation and TAU phosphorylation in the hippocampus. In addition, impairments of brain insulin signaling elicited by long-term HFD were restored by MLT treatment, as confirmed by ex vivo insulin stimulation. Importantly, MLT reversed HFD-induced cognitive decline as measured by a water maze test, normalized hippocampal LTP and restored CREB activity and BDNF levels as well as cholinergic neuronal activity in the hippocampus. Collectively, these findings indicate that MLT may exhibit substantial protective effects on cognition, via restoration of brain insulin signaling.

分类号：

  • 相关文献
作者其他论文 更多>>

微信小程序