School of Life Science, PR China.
MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, 510631, PR China.
Eur J Pharmacol. 2019 Jun 15;853:325-335. doi: 10.1016/j.ejphar.2019.04.015. Epub 2019 Apr 10.
Cerebral ischemia impairs physiological form of synaptic plasticity such as long-term potentiation (LTP). Clinical symptoms of cognitive dysfunction resulting from cerebral ischemia are associated with neuron loss and synaptic function impairment in hippocampus. It has been widely reported that cordycepin displays neuroprotective effect on ameliorating cognitive dysfunction induced by cerebral ischemia. Therefore, it is necessary to study whether cordycepin recovers cognitive function after brain ischemia through improving LTP induction. However, there has been very little discussion about the effects of cordycepin on LTP of cerebral ischemia so far. In the present study, we investigated the effects of cordycepin on LTP impairment and neuron loss induced by cerebral ischemia and excitotoxicity, using electrophysiological recording and Nissl staining techniques. The models were obtained by bilateral common carotid artery occlusion (BCCAO) and intrahippocampal NMDA microinjection. We also explored whether adenosine A receptors involve in the neuroprotection of cordycepin by using western blot. We found that cordycepin remarkably alleviated LTP impairment and protected pyramidal cell of hippocampal CA1 region against cerebral ischemia and excitotoxicity. Meanwhile, cordycepin prevented the reduction on adenosine A receptor level caused by ischemia but did not alter the adenosine A receptor level in hippocampal CA1 area. The improvement of LTP in the excitotoxic rats after cordycepin treatment could be blocked by DPCPX, a selective antagonist of adenosine A receptor. In summary, our findings provided new insights into the mechanisms of cordycepin neuroprotection in excitotoxic diseases, which is through regulating adenosine A receptor to improve LTP formation and neuronal survival.
脑缺血会损害突触可塑性的生理形式，如长时程增强（LTP）。脑缺血引起的认知功能障碍的临床症状与海马神经元丢失和突触功能障碍有关。已有广泛报道称，蛹虫草素有改善脑缺血引起的认知功能障碍的神经保护作用。因此，有必要研究蛹虫草素是否通过改善 LTP 诱导来恢复脑缺血后的认知功能。然而，到目前为止，关于蛹虫草素对脑缺血 LTP 的影响，还很少有讨论。在本研究中，我们使用电生理记录和尼氏染色技术，研究了蛹虫草素对脑缺血和兴奋性毒性引起的 LTP 损伤和神经元丢失的影响。模型通过双侧颈总动脉闭塞（BCCAO）和海马内 NMDA 微注射获得。我们还通过 Western blot 探讨了腺苷 A 受体是否参与蛹虫草素的神经保护作用。结果发现，蛹虫草素可显著减轻 LTP 损伤，保护海马 CA1 区锥体神经元免受脑缺血和兴奋性毒性的影响。同时，蛹虫草素可防止缺血引起的腺苷 A 受体水平降低，但不改变海马 CA1 区的腺苷 A 受体水平。DPCPX（腺苷 A 受体的选择性拮抗剂）可阻断蛹虫草素处理后的兴奋性毒性大鼠 LTP 的改善。总之，我们的研究结果为蛹虫草素在兴奋性疾病中的神经保护机制提供了新的见解，即通过调节腺苷 A 受体来改善 LTP 形成和神经元存活。
