Cordycepin Ameliorates Synaptic Dysfunction and Dendrite Morphology Damage of Hippocampal CA1 via A1R in Cerebral Ischemia

Zhao-Hui Chen; Yuan-Yuan Han; Ying-Jie Shang; Si-Yi Zhuang; Jun-Ni Huang; Bao-Yan Wu; Chu-Hua Li

doi:10.3389/fncel.2021.783478

Cordycepin Ameliorates Synaptic Dysfunction and Dendrite Morphology Damage of Hippocampal CA1 via A1R in Cerebral Ischemia

Front Cell Neurosci. 2021 Dec 24:15:783478. doi: 10.3389/fncel.2021.783478. eCollection 2021.

Authors

Zhao-Hui Chen¹, Yuan-Yuan Han^{1

2}, Ying-Jie Shang¹, Si-Yi Zhuang¹, Jun-Ni Huang¹, Bao-Yan Wu³, Chu-Hua Li¹

Affiliations

¹ School of Life Science, South China Normal University, Guangzhou, China.
² Panyu Central Hospital, Guangzhou, China.
³ Ministry of Education (MOE) Key Laboratory of Laser Life Science, Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, China.

Abstract

Cordycepin exerted significant neuroprotective effects and protected against cerebral ischemic damage. Learning and memory impairments after cerebral ischemia are common. Cordycepin has been proved to improve memory impairments induced by cerebral ischemia, but its underlying mechanism has not been revealed yet. The plasticity of synaptic structure and function is considered to be one of the neural mechanisms of learning and memory. Therefore, we investigated how cordycepin benefits dendritic morphology and synaptic transmission after cerebral ischemia and traced the related molecular mechanisms. The effects of cordycepin on the protection against ischemia were studied by using global cerebral ischemia (GCI) and oxygen-glucose deprivation (OGD) models. Behavioral long-term potentiation (LTP) and synaptic transmission were observed with electrophysiological recordings. The dendritic morphology and histological assessment were assessed by Golgi staining and hematoxylin-eosin (HE) staining, respectively. Adenosine A1 receptors (A1R) and adenosine A2A receptors (A2AR) were evaluated with western blotting. The results showed that cordycepin reduced the GCI-induced dendritic morphology scathing and behavioral LTP impairment in the hippocampal CA1 area, improved the learning and memory abilities, and up-regulated the level of A1R but not A2AR. In the in vitro experiments, cordycepin pre-perfusion could alleviate the hippocampal slices injury and synaptic transmission cripple induced by OGD, accompanied by increased adenosine content. In addition, the protective effect of cordycepin on OGD-induced synaptic transmission damage was eliminated by using an A1R antagonist instead of A2AR. These findings revealed that cordycepin alleviated synaptic dysfunction and dendritic injury in ischemic models by modulating A1R, which provides new insights into the pharmacological mechanisms of cordycepin for ameliorating cognitive impairment induced by cerebral ischemia.

Keywords: adenosine A1 receptors; cerebral ischemia; cordycepin; dendritic morphology; learning and memory (neurosciences); synaptic function.