title: Resveratrol Attenuates Aβ-Induced Early Hippocampal Neuron Excitability Impairment via Recovery of Function of Potassium Channels.
abstract: Alzheimer's disease (AD) is an age-related neurodegenerative disease. Amyloid-β (Aβ) is not only the morphological hallmark but also the initiator of the pathology process of AD. As a natural compound found in grapes, resveratrol shows a protective effect on the pathophysiology of AD, but the underlying mechanism is not very clear. This study was to investigate whether resveratrol could attenuate Aβ-induced early impairment in hippocampal neuron excitability and the underlying mechanism. The excitability and voltage-gated potassium currents were examined in rat hippocampal CA1 pyramidal neurons by using whole-cell patch-clamp technique. It was found that Aβ25-35increased the excitability of neurons. Resveratrol could reverse the Aβ25-35-induced increase in the frequency of repetitive firing and the spike half-width of action potential (AP). Moreover, resveratrol can attenuate Aβ25-35-induced decreases in transient potassium channel (IA) and delay rectifier potassium channel (IK(DR)) of neurons. It was also found that resveratrol could decline the increase of protein kinase A (PKA) and inhibit the activation of PI3K/Akt signaling pathway induced by Aβ25-35. The results suggest that resveratrol alleviates Aβ25-35-induced dysfunction in hippocampal CA1 pyramidal neurons via recovery of the function of IAand IK(DR)by inhibiting the increase of PKA and the activation of PI3K/Akt signaling pathway.
authors.affiliation: School of Medicine, State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, People's Republic of China.
authors.forename: Hongqiang
authors.initials: H
authors.lastname: Yin
authors.affiliation: College of Life Sciences and Key Laboratory of Bioactive Materials Ministry of Education, Nankai University, Tianjin, 300071, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: College of Life Sciences and Key Laboratory of Bioactive Materials Ministry of Education, Nankai University, Tianjin, 300071, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: School of Medicine, State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, People's Republic of China.|Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300200, People's Republic of China.
authors.forename: Na
authors.initials: N
authors.lastname: Gao
authors.affiliation: College of Life Sciences and Key Laboratory of Bioactive Materials Ministry of Education, Nankai University, Tianjin, 300071, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: School of Medicine, State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, People's Republic of China. zhuoyang@nankai.edu.cn.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D015153:Blotting, Western; D056547:CA1 Region, Hippocampal / Q000187:drug effects* / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000378:metabolism / Q000633:toxicity*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D017966:Pyramidal Cells / Q000187:drug effects* / Q000378:metabolism; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D046509:Tissue Culture Techniques
chemical_list: D016229:Amyloid beta-Peptides; D017868:Cyclic AMP-Dependent Protein Kinases; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D015221:Potassium Channels; D000077185:Resveratrol; D013267:Stilbenes; C074636:amyloid beta-protein (25-35)
keywords: Action potential; Alzheimer’s disease; Patch clamp; Potassium currents; Resveratrol