Melatonin Premedication Attenuates Isoflurane Anesthesia-Induced β-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 β-amyloid (Aβ) generation, inhibit formation of β-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 whether melatonin can attenuate Aβ1-40 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 Aβ1-40 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 Aβ1-40 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 Aβ1-40 generation and cholinergic dysfunction, and further work is necessary to clarify its target sites and detailed mechanisms. [ABSTRACT FROM AUTHOR]