title: Melatonin premedication attenuates isoflurane anesthesia-induced β-amyloid generation and cholinergic dysfunction in the hippocampus of aged rats.
abstract: 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 Aβ(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 Aβ(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 Aβ(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 Aβ(1-40) generation and cholinergic dysfunction, and further work is necessary to clarify its target sites and detailed mechanisms.
authors.affiliation: Department of Anesthesiology, Peking University Third Hospital, Beijing, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Ni
authors.forename: Gang
authors.initials: G
authors.lastname: Tan
authors.forename: Ailun
authors.initials: A
authors.lastname: Luo
authors.forename: Min
authors.initials: M
authors.lastname: Qian
authors.forename: Yi
authors.initials: Y
authors.lastname: Tang
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhou
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Donglin
authors.initials: D
authors.lastname: Jia
authors.forename: Changyi
authors.initials: C
authors.lastname: Wu
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Guo
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D059329:Cholinergic Neurons / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D008550:Melatonin / Q000494:pharmacology* / Q000627:therapeutic use; D009410:Nerve Degeneration / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control; D010446:Peptide Fragments / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016229:Amyloid beta-Peptides; D018685:Anesthetics, Inhalation; D000975:Antioxidants; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D007530:Isoflurane; D002795:Choline O-Acetyltransferase; D008550:Melatonin