Melatonin Premedication Attenuates Isoflurane Anesthesia-Induced β-Amyloid Generation and Cholinergic Dysfunction in the Hippocampus of Aged Rats

作者：Ni, Cheng; Tan, Gang; Luo, Ailun; Qian, Min; Tang, Yi; Zhou, Yang; Wang, Jun; Li, Min; Zhang, Yan; Jia, Donglin; Wu, Changyi; Guo, Xiangyang^*

来源：International Journal of Neuroscience, 2013, 123(4): 213-220.

DOI：10.3109/00207454.2012.742895

• beta-amyloid
• choline acetyltransferase
• hippocampus
• isoflurane
• melatonin

Melatonin plays an important role in aging and relevant neurodegeneration as an antioxidant and neuroprotector. It can interact with beta-amyloid (A beta) generation, inhibit formation of beta-sheet and amyloid fibrils, modulate apoptosis, and protect cholinergic system function in Alzheimer's disease animal model. Recently, its effects on anesthetic-induced neurodegeneration have received more attention, and in this investigation, we explored whethermelatonin can attenuate A beta(1-40) generation and cholinergic dysfunction in the hippocampus of aged rats induced by isoflurane through enzyme-linked immunosorbent assay, Western blot, immunohistochemistry, and immunofluorescence. The results showed that isoflurane increased A beta(1-40) generation and caused cholinergic dysfunction through decreasing choline acetyltransferase (ChAT) expression in the hippocampus in a dose-dependent way, and intraperitoneal melatonin premedication attenuated the neurodegeneration through inhibiting A beta(1-40) generation and increasing ChAT expression, and its effects were more obvious in high-concentration isoflurane group. Collectively, our results provide evidence for the therapeutic value of melatonin on isoflurane-induced neurodegeneration, including A beta(1-40) generation and cholinergic dysfunction, and further work is necessary to clarify its target sites and detailed mechanisms.

• 出版日期2013-4
• 单位中国医学科学院北京协和医院; 北京大学