Cordycepin protects against β-amyloid and ibotenic acid-induced hippocampal CA1 pyramidal neuronal hyperactivity
10.4196/kjpp.2019.23.6.483
- Author:
Li Hua YAO
1
;
Jinxiu WANG
;
Chao LIU
;
Shanshan WEI
;
Guoyin LI
;
Songhua WANG
;
Wei MENG
;
Zhi Bin LIU
;
Li Ping HUANG
Author Information
1. School of Life Science, Jiangxi Science & Technology Normal University, Nanchang, Jiangxi 330013, PR China.
- Publication Type:Original Article
- Keywords:
Adenosine A₁ receptor;
Alzheimer disease;
Cordycepin;
Excitotoxicity;
Neuroprotection
- MeSH:
Action Potentials;
Adenosine;
Alzheimer Disease;
Fires;
Ibotenic Acid;
Membranes;
Neurons;
Neuroprotection;
Neuroprotective Agents;
Patch-Clamp Techniques;
Pyramidal Cells
- From:The Korean Journal of Physiology and Pharmacology
2019;23(6):483-491
- CountryRepublic of Korea
- Language:English
-
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.
