title: Rhynchophylline Protects Against the Amyloid β-Induced Increase of Spontaneous Discharges in the Hippocampal CA1 Region of Rats.
abstract: Accumulated soluble amyloid β (Aβ)-induced aberrant neuronal network activity has been recognized as a key causative factor leading to cognitive deficits which are the most outstanding characteristic of Alzheimer's disease (AD). As an important structure associated with learning and memory, the hippocampus is one of the brain regions that are impaired very early in AD, and the hippocampal CA1 region is selectively vulnerable to soluble Aβ oligomers. Our recent study showed that soluble Aβ1-42 oligomers induced hyperactivity and perturbed the firing patterns in hippocampal neurons. Rhynchophylline (RIN) is an important active tetracyclic oxindole alkaloid isolated from Uncaria rhynchophylla which is a traditional Chinese medicine and often used to treat central nervous system illnesses such as hypertension, convulsions, tremor, stroke etc. Previous evidence showed that RIN possessed neuroprotective effects of improving the cognitive function of mice with Alzheimer-like symptoms. In the present study, we aimed to investigate the protective effect of RIN against soluble Aβ1-42 oligomers-induced hippocampal hyperactivity. The results showed that (1) the mean frequency of spontaneous discharge was increased by the local application of 3 μM soluble Aβ1-42 oligomers; (2) 30 μM RIN did not exert any obvious effects on basal physiological discharges; and (3) treatment with RIN effectively inhibited the soluble Aβ1-42 oligomers-induced enhancement of spontaneous discharge, in a concentration-dependent manner with an IC50 = 9.0 μM. These in vivo electrophysiological results indicate that RIN can remold the spontaneous discharges disturbed by Aβ and counteract the deleterious effect of Aβ1-42 on neural circuit. The experimental findings provide further evidence to affirm the potential of RIN as a worthy candidate for further development into a therapeutic agent for AD.
authors.affiliation: Department of Physiology, Third Military Medical University, Gaotanyan Street 30, Chongqing, 400038, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Shao
authors.affiliation: Department of Physiology, Third Military Medical University, Gaotanyan Street 30, Chongqing, 400038, People's Republic of China.
authors.forename: Ze
authors.initials: Z
authors.lastname: Mi
authors.affiliation: Department of Chemistry, Third Military Medical University, Gaotanyan Street 30, Chongqing, 400038, People's Republic of China.
authors.forename: Wei-gang
authors.initials: WG
authors.lastname: Ji
authors.affiliation: Department of Physiology, Third Military Medical University, Gaotanyan Street 30, Chongqing, 400038, People's Republic of China.
authors.forename: Cheng-huan
authors.initials: CH
authors.lastname: Zhang
authors.affiliation: Department of Physiology, Third Military Medical University, Gaotanyan Street 30, Chongqing, 400038, People's Republic of China.
authors.forename: Teng
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Physiology, Third Military Medical University, Gaotanyan Street 30, Chongqing, 400038, People's Republic of China.
authors.forename: Shuan-cheng
authors.initials: SC
authors.lastname: Ren
authors.affiliation: Department of Physiology, Third Military Medical University, Gaotanyan Street 30, Chongqing, 400038, People's Republic of China. zhuzr2013@163.com.
authors.forename: Zhi-ru
authors.initials: ZR
authors.lastname: Zhu
mesh_terms: D017772:Amyloid Neuropathies / Q000503:physiopathology* / Q000517:prevention & control* / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects* / Q000503:physiopathology*; D003072:Cognition Disorders / Q000139:chemically induced / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D026121:Indole Alkaloids / Q000494:pharmacology*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D000078183:Oxindoles; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D032070:Uncaria / Q000737:chemistry
chemical_list: D016229:Amyloid beta-Peptides; D026121:Indole Alkaloids; D018696:Neuroprotective Agents; D000078183:Oxindoles; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C052714:rhyncophylline
keywords: Hippocampal CA1 region; In vivo; Rhynchophylline; Soluble Aβ1–42 oligomers; Spontaneous discharge