| Title | Melatonin prevents diabetes-associated cognitive dysfunction from microglia-mediated neuroinflammation by activating autophagy via TLR4/Akt/mTOR pathway |
| Authors | Cui, Yixin Yang, Mengmeng Wang, Yilin Ren, Jianmin Lin, Peng Cui, Chen Song, Jia He, Qin Hu, Huiqing Wang, Kexin Sun, Yu |
| Affiliation | Shandong Univ, Qilu Hosp, Dept Endocrinol, Jinan, Peoples R China Shandong Univ, Inst Endocrine & Metab Dis, Jinan, Peoples R China Peking Univ, Dept Traumat Orthoped, Peoples Hosp, Beijing, Peoples R China Shandong Prov Med & Hlth, Key Lab Endocrine & Metab Dis, Jinan, Peoples R China Jinan Clin Res Ctr Endocrine & Metab Dis, Jinan, Peoples R China Shandong Univ, Qilu Hosp, Dept Gen Surg, Jinan 250012, Shandong, Peoples R China |
| Issue Date | Apr-2021 |
| Publisher | FASEB JOURNAL |
| Abstract | Cognitive dysfunction often occurs in diabetes mellitus patients. This study aimed to investigate the efficacy of melatonin (MLT) in improving diabetes-associated cognitive decline and the underlying mechanism involved. Type 2 diabetic mice and palmitic acid (PA)-stimulated BV-2 cells were treated by MLT, and the potential mechanisms among MLT, cognition, and autophagy were explored. The results showed that type 2 diabetic mice showed obvious learning and memory impairments in the Morris water maze test compared with normal controls, which could be ameliorated by MLT treatment. Meanwhile, MLT administration significantly improved neuroinflammation and regulated microglial apoptosis. Furthermore, autophagy inhibitor 3-methyladenine (3-MA) increased the microglial inflammation and apoptosis, indicating that the treatment effect of MLT was mediated by autophagy. Lastly, MLT treatment significantly decreased the levels of toll-like receptors 4 (TLR4), phosphorylated-protein kinase B (Akt), and phosphorylated-mechanistic target of rapamycin (mTOR), indicating that blocking TLR4/Akt/mTOR pathway might be an underlying basis for the anti-inflammatory and anti-apoptosis effects of MLT. Collectively, our study suggested that MLT could improve learning and memory in type 2 diabetic mice by activating autophagy via the TLR4/Akt/mTOR pathway, thereby inhibiting neuroinflammation and microglial apoptosis. |
| URI | http://hdl.handle.net/20.500.11897/611374 |
| ISSN | 0892-6638 |
| DOI | 10.1096/fj.202002247RR |
| Indexed | SCI(E) |
| Appears in Collections: | 人民医院 |
