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Original Article

Korean J Physiol Pharmacol 2019; 23(6): 483-491

Published online November 1, 2019 https://doi.org/10.4196/kjpp.2019.23.6.483

Copyright © The Korean Journal of Physiology & Pharmacology.

Cordycepin protects against β–amyloid and ibotenic acid–induced hippocampal CA1 pyramidal neuronal hyperactivity

Li-Hua Yao1,3, Jinxiu Wang1, Chao Liu2, Shanshan Wei1, Guoyin Li3, Songhua Wang1, Wei Meng1, Zhi-Bin Liu3, and Li-Ping Huang2,*

1School of Life Science, Jiangxi Science & Technology Normal University, Nanchang, Jiangxi 330013, 2School of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi 330004, 3School of Sport Science, Jiangxi Science & Technology Normal University, Nanchang, Jiangxi 330013, PR China

Correspondence to:Li-Ping Huang
E-mail: 286529404@qq.com

Received: June 4, 2019; Revised: July 29, 2019; Accepted: August 12, 2019

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Cordycepin exerts neuroprotective effects against excitotoxic neuronal death. However, its direct electrophysiological evidence in Alzheimer's disease (AD) remains unclear. This study aimed to explore the electrophysiological mechanisms underlying the protective effect of cordycepin against the excitotoxic neuronal insult in AD using whole-cell patch clamp techniques. β-Amyloid (Aβ) and ibotenic acid (IBO)–induced injury model in cultured hippocampal neurons was used for the purpose. The results revealed that cordycepin significantly delayed Aβ + IBO–induced excessive neuronal membrane depolarization. It increased the onset time/latency, extended the duration, and reduced the slope in both slow and rapid depolarization. Additionally, cordycepin reversed the neuronal hyperactivity in Aβ + IBO–induced evoked action potential (AP) firing, including increase in repetitive firing frequency, shortening of evoked AP latency, decrease in the amplitude of fast afterhyperpolarization, and increase in membrane depolarization. Further, the suppressive effect of cordycepin against Aβ + IBO–induced excessive neuronal membrane depolarization and neuronal hyperactivity was blocked by DPCPX (8-cyclopentyl-1,3-dipropylxanthine, an adenosine A1 receptor–specific blocker). Collectively, these results revealed the suppressive effect of cordycepin against the Aβ + IBO–induced excitotoxic neuronal insult by attenuating excessive neuronal activity and membrane depolarization, and the mechanism through the activation of A1R is strongly recommended, thus highlighting the therapeutic potential of cordycepin in AD.

Keywords: Adenosine A1 receptor, Alzheimer disease, Cordycepin, Excitotoxicity, Neuroprotection