Melatonin Premedication Attenuates Isoflurane Anesthesia-Induced Beta-Amyloid Generation And Cholinergic Dysfunction In The Hippocampus Of Aged Rats

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.