Adenosine A1 Receptors Plays An Important Protective Role In Epilepsy Related Cognitive Impairment

Objective:This part intends to investigate the protective role of adenosine A1 receptors in decreasing learning and memory function impairment and neuronal death of epileptic mice.Methods:Animal epileptic model was established in adenosine A1 receptors knockout and wide type mice by intraperitoneal injection of pentylenetetrazol.Morris water-maze test was used to evaluate space learning and memory function.Nissl staining was used to determine the neuronal loss and active caspase-3 expression was investigated by immunohistochemistry staining and Western Blot analysis to detect the cell apoptosis after pentylenetetrazol kindling.Results:Adenosine A1 receptors knockout significantly extended the escape latency compared with wide type group after pentylenetetrazol kindling.The number of surviving neurons was significantly decreased in epileptic adenosine A1 receptors knockout mice.And the expression of hippocampal active caspase-3 was upregulated more seriously in A1 receptors knockout mice compared with wide type ones.Conclusions:Adenosine A1 receptors protect the cognitive function and attenuate the neuronal injuries of epileptic mice.Objective:This part intends to illustrate the effects of adenosine Al receptors on CA3-CAI long-term potentiation and hippocampal synaptic proteins expressions.Method:Animal epileptic model was established in adenosine A1 receptors knockout mice and wide type mice by intraperitoneal injection of pentylenetetrazol.CA3-CA1 Long-term Potentiation(LTP)was induced by tetanic burst and recorded in hippocampus slices.Western Blot analysis was used to evaluate the protein expression of PSD95,brain-derived neurotrophic factor(BDNF)and glutamate receptor subtypes.Result:The LTP was inhibited in epileptic mice induced by pentylenetetrazol.Adenosine A1 receptors knockout exacerbated the inhibition of LTP compared with wide type ones.The expression of PSD95 and BDNF was significantly decreased at 7 days after kindling in knockout mice compared with wide type ones.Glutamate NMDAR2B was upregulated at 7 days after kindling with less increase in knockout mice compared with wide type ones.The other glutamate receptor subtypes showed no significant difference between the two genotypes.Conclusion:Adenosine A1 receptors attenuated the CA3-CA1 pathway LTP inhibition caused by pentylenetetrazol kindling and the protective role may act through modulating the expression of PSD95 and BDNF.