The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Cordycepin protects against β-amyloid and ibotenic acid-induced hippocampal CA1 pyramidal neuronal hyperactivity

  • Yao, Li-Hua (School of Life Science, Jiangxi Science & Technology Normal University) ;
  • Wang, Jinxiu (School of Life Science, Jiangxi Science & Technology Normal University) ;
  • Liu, Chao (School of Pharmacy, Jiangxi University of Traditional Chinese Medicine) ;
  • Wei, Shanshan (School of Life Science, Jiangxi Science & Technology Normal University) ;
  • Li, Guoyin (School of Sport Science, Jiangxi Science & Technology Normal University) ;
  • Wang, Songhua (School of Life Science, Jiangxi Science & Technology Normal University) ;
  • Meng, Wei (School of Life Science, Jiangxi Science & Technology Normal University) ;
  • Liu, Zhi-Bin (School of Sport Science, Jiangxi Science & Technology Normal University) ;
  • Huang, Li-Ping (School of Pharmacy, Jiangxi University of Traditional Chinese Medicine)
  • Received : 2019.06.04
  • Accepted : 2019.08.12
  • Published : 2019.11.01
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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. ${\beta}$-Amyloid ($A{\beta}$) and ibotenic acid (IBO)-induced injury model in cultured hippocampal neurons was used for the purpose. The results revealed that cordycepin significantly delayed $A{\beta}$ + 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 $A{\beta}$ + 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 $A{\beta}$ + IBO-induced excessive neuronal membrane depolarization and neuronal hyperactivity was blocked by DPCPX (8-cyclopentyl-1,3-dipropylxanthine, an adenosine $A_1$ receptor-specific blocker). Collectively, these results revealed the suppressive effect of cordycepin against the $A{\beta}$ + IBO-induced excitotoxic neuronal insult by attenuating excessive neuronal activity and membrane depolarization, and the mechanism through the activation of $A_1R$ is strongly recommended, thus highlighting the therapeutic potential of cordycepin in AD.

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References

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