title: Melatonin protects against amyloid-β-induced impairments of hippocampal LTP and spatial learning in rats.
abstract: Alzheimer's disease (AD), the most prevalent neurodegenerative disease in the elderly, leads to progressive loss of memory and cognitive deficits. Amyloid-β protein (Aβ) in the brain is thought to be the main cause of memory loss in AD. Melatonin, an indole hormone secreted by the pineal gland, has been reported to produce neuroprotective effects. We examined whether melatonin could protect Aβ-induced impairments of hippocampal synaptic plasticity, neuronal cooperative activity, and learning and memory. Rats received bilateral intrahippocampal injection of Aβ1-42 or Aβ31-35 followed by intraperitoneal application of melatonin for 10 days, and the effects of chronic melatonin treatment on in vivo hippocampal long-term potentiation (LTP) and theta rhythm and Morris water maze performance were examined. We showed that intrahippocampal injection of Aβ1-42 or Aβ31-35 impaired hippocampal LTP in vivo, while chronic melatonin treatment reversed Aβ1-42- or Aβ31-35-induced impairments in LTP induction. Intrahippocampal injection of Aβ31-35 impaired spatial learning and decreased the power of theta rhythm in the CA1 region induced by tail pinch, and these synaptic, circuit, and learning deficits were rescued by chronic melatonin treatment. These results provide evidence for the neuroprotective action of melatonin against Aβ insults and suggest a strategy for alleviating cognition deficits of AD.
authors.affiliation: Department of Physiology, Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001, China.
authors.forename: Xiao-Jie
authors.initials: XJ
authors.lastname: Liu
authors.forename: Li
authors.initials: L
authors.lastname: Yuan
authors.forename: Dong
authors.initials: D
authors.lastname: Yang
authors.forename: Wei-Na
authors.initials: WN
authors.lastname: Han
authors.forename: Qing-Shan
authors.initials: QS
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.forename: Qing-Song
authors.initials: QS
authors.lastname: Liu
authors.forename: Jin-Shun
authors.initials: JS
authors.lastname: Qi
mesh_terms: D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008550:Melatonin / Q000008:administration & dosage / Q000494:pharmacology*; D008568:Memory / Q000187:drug effects; D010446:Peptide Fragments / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C113042:amyloid beta-protein (31-35); D008550:Melatonin
keywords: Morris water maze; amyloid β-protein; local field potential; long-term potentiation; melatonin