Cordycepin ameliorates synaptic dysfunction and dendrite morphology
impairments induced by cerebral ischemia via adenosine A1 receptors in
vitro and in vivo
Abstract
Background and aims: Cordycepin has been proved to have neuroprotection
and to improve learning and memory in cerebral ischemia. However, the
potential mechanisms are unclear so far. Plasticy 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
ischemic models. Experimental Approach: The impact of cordycepin was
studied using oxygen glucose deprivation (OGD) and global cerebral
ischemia (GCI) models. Synaptic transmission and behavioral long-term
potentiation (LTP) were investigated with electrophysiological
recordings. Dendritic morphology was assessed by Golgi staining. The
densities of adenosine A1 and A2A receptors (A1R and A2AR) were
evaluated with western blots and immunofluorescence. Key Results:
Cordycepin alleviated the ischemia-induced damages of dendritic
morphology and behavioral LTP in hippocampal CA1 area, improved the
learning and memory abilities and up-regulated the expression of A1R but
not A2AR in hippocampus of GCI rats. In the in vitro experiments,
cordycepin pre-perfusion could reduce the hippocampal slices injury and
synaptic transmission impairment induced by OGD, improved adenosine
content and reduced the expression of A1R but did not alter A2AR.
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 vivo
and in vitro ischemic models by modulating A1R, which may be the neural
mechanisms of cordycepin to improve learning and memory in cerebral
ischemic animals.