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

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.

Bioactive natural products in COVID-19 therapy

“…For example, cordycepin plays a key role in long-term neuroprotection for traumatic brain injury (through inhibiting neutrophil infiltration and preserving neuroinflammation), (Wei et al, 2021) protecting diabetic hearts from ischemia/reperfusion injury (via up-regulating AMPK/Mfn2-dependent mitochondrial fusion and expression), (Yu et al, 2021) and ameliorating cerebral ischemic damage (via improving the memory ability, up-regulating the level of adenosine A1 receptors, and reducing dendritic morphology scathing). (Chen et al, 2021). Thus, cordycepin has its advantages in organ protection and broad-spectrum antiviral activities.…”

Excitatory Synaptic Transmission in Ischemic Stroke: A New Outlet for Classical Neuroprotective Strategies

“…Clinical imaging confirmed that by targeting synaptic vesicular protein 2A, the synaptic density of stroke patients with 21 ± 8 days of onset was significantly lower than that of healthy controls [ 19 ]. Imaging results in the hippocampal CA1 region following global cerebral ischemia (GCI) in rats also indicate significant damage to synaptic structures, as manifested by the reduced length and density of dendrites and spinous processes [ 20 ]. In the cerebral artery occlusion (MCAO) mice after reperfusion, the synaptic superstructure was damaged, probably attributed to the failure of dynamic turnover of synaptic proteins [ 21 ].…”