Korean J Physiol Pharmacol.  2019 Nov;23(6):483-491. 10.4196/kjpp.2019.23.6.483.

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

Affiliations
  • 1School of Life Science, Jiangxi Science & Technology Normal University, Nanchang, Jiangxi 330013, PR China.
  • 2School of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi 330004, PR China. 286529404@qq.com
  • 3School of Sport Science, Jiangxi Science & Technology Normal University, Nanchang, Jiangxi 330013, PR China.

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.

Keyword

Adenosine A₁ receptor; Alzheimer disease; Cordycepin; Excitotoxicity; Neuroprotection

MeSH Terms

Action Potentials
Adenosine
Alzheimer Disease
Fires
Ibotenic Acid
Membranes
Neurons
Neuroprotection
Neuroprotective Agents
Patch-Clamp Techniques
Pyramidal Cells*
Adenosine
Ibotenic Acid
Neuroprotective Agents
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