Cordycepin ameliorates synaptic dysfunction and dendrite morphology
damage of hippocampal CA1 via A1R in cerebral ischemia
Abstract
Background and Aims: Cerebral ischemia always led to learning and memory
impairments. Cordycepin has been proved to improve cognition but the
potential mechanisms are unclear so far. Plasticity of synaptic
structure and synaptic function are considered as the neural mechanisms
of learning and memory. Therefore, we investigated the effects of
cordycepin on dendritic morphology and synaptic function in cerebral
ischemia and explored the relevant molecular mechanisms. Experimental
Approach: The impact of cordycepin was studied using global cerebral
ischemia (GCI) and oxygen glucose deprivation (OGD) models. Behavioral
long-term potentiation (LTP) and synaptic transmission were investigated
with electrophysiological recordings. Dendritic morphology and
histological assessment were assessed by Golgi staining and HE staining,
respectively. And the densities of adenosine receptors and adenosine
content were evaluated with western blotting and HPLC, respectively. Key
Results: Cordycepin alleviated the GCI-induced damages of dendritic
morphology and behavioral LTP in hippocampal CA1, and improved the
learning and memory abilities and up-regulated the expression of A1R but
not A2AR. In the in vitro experiments, cordycepin pre-perfusion could
reduce the hippocampal slices injury and synaptic transmission
impairment induced by OGD, accompanied with the increase of adenosine
content. Furthermore, the protection of cordycepin on synaptic
transmission against OGD was eliminated by using the antagonist of A1R
instead of A2AR. Conclusion and Implications: These findings indicated
that cordycepin alleviated synaptic dysfunction and dendritic injury in
ischemia by modulating A1R, which provide conclusive evidence that
cordycepin could be used as potential drug for the treatment of
cognitive impairment induced by cerebral ischemia