Protective Effect Of Cordycepin Against The Glu-induced Excitatory Neurotoxicity

Although glutamate is one of the most vital excitatory neurotransmitters of the central nervous system,its excessive extracellular concentration leads to uncontrolled continuous depolarization of neurons,a poisonous process called,excitotoxicity.The experimental studies have shown that excitatory toxicity caused by glutamate leads to increased intracellular Ca²⁺levels,dysfunction of mitochondria,ROS production and ER stress.Excessive calcium concentration is the key mediator of glutamate toxicity through over activation of ionotropic and metabotropic receptors.In addition,glutamate accumulation can also inhibit cystine?Cy SS?uptake by reversing the action of the Cy SS/glutamate antiporter.Reversal of the antiporter action reinforces the aforementioned events by depleting neurons of cysteine and reducing the potential of glutathione.Furthermore,Excessive increase of intracellular calcium concentration can react on mitochondria,causing their permeability change and dysfunction,leading to the death of neurons,further inducing the loss of nerve spines,synaptic dysfunction,neural network failure and cognitive dysfunction.Cordycepin?3-deoxyadenosine?,an active ingredient of C.militaris,exerts antibacterial,anti-inflammatory,anti-tumor,anti-hypertension,anti-oxidation and the protection of lung and kidney.A number of studies have shown that cordycepin influences the central nervous system and plays neuroprotective effects.In addition,there is growing evidence that cordycepin plays a protective effect against injure resulting from ischemia/reperfusion insult by abnormal free radical scavenging activity,control of neuron hyperactivity.These studies indicate that the protective effect of cordycepin may be concerned with the antioxidant and anti-excitatory neurotoxicity.In view of the close connection between excitatory neurotoxicity and oxidative stress induced by Glu on CNS,cordycepin might be have a neuroprotective effect on the injury induced by Glu,preventing the Glu-related neurodegenerative diseases.But indeed,the exact neuroprotective effect of cordycepin on CNS injury induced by Glu is yet to be elucidated.In this study,our objective to investigate the protective effect of cordycepin on Glu-induced nerve injury model used by MTT,fluorescent probe and Visible spectrophotometer technique and molecular biological method.1.The protective effect of cordycepin on the Glu-induced neurotoxicity injury models were investigated in cell:The primary hippocampal neurons induced by Glu were used as the nerve injury model,and the results showed that cordycepin increased the cell viability.2.Fluorescence imaging was used to study the effects of cordycepin on apoptosis,intracellular Ca²⁺dependent fluorescence and ROS production in Glu-induced neuronal injury cell models.The results showed that cordycepin could significantly inhibit Glu-induced cell death,improved cell viability,reduced the production of ROS,and decreased Ca²⁺levels.3.The effects of cordycepin on ACh E and glutathione in the cell model of glutamate-induced nerve injury were studied by visible spectrophotometry.The results showed that cordycepin reduced the overactivation of acetylcholinesterase and the increase of glutathione in neurons.4.The protective scheme of cordycepin against the Glu-induced neurotoxicity injury model:in this part of the study,experiments were demonstrated the neuroprotection of cordycepin depends on activation of the adenosine A1 receptor.In summary,this result indicates that cordycepin had a protective effect on neurotoxicity injury model induced by Glu,and the related scheme may be concerned with the decrease of oxidative stress level,the recoverer of calcium homeostasis,and the enhancement of GSH levels in hippocampus.And that adenosine A1 receptor blockers can interdict the function of cordycepin,showing that cordycepin might show neuroprotective effects on the Glu-induced neuronal injury cell models,via the A1R activation.