School of Life Science, South China Normal University, Guangzhou, China.
MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, China.
J Neurochem. 2019 Oct;151(1):79-90. doi: 10.1111/jnc.14826. Epub 2019 Aug 22.
Cordycepin, an adenosine analog, has been reported to improve cognitive function, but which seems to be inconsistent with the reports showing that cordycepin inhibited long-term potentiation (LTP). Behavioral-LTP is usually used to study long-term synaptic plasticity induced by learning tasks in freely moving animals. In order to investigate simultaneously the effects of cordycepin on LTP and behavior in rats, we applied the model of behavioral-LTP induced by Y-maze learning task through recording population spikes in hippocampal CA1 region. Golgi staining and Sholl analysis were employed to assess the morphological structure of dendrites in pyramidal cells of hippocampal CA1 area, and western blotting was used to examine the level of adenosine A1 receptors and A2A receptors (A2AR). We found that cordycepin significantly improved behavioral-LTP magnitude, accompanied by increases in the total length of dendrites, the number of intersections and spine density but did not affect Y-maze learning task. Furthermore, cordycepin obviously reduced A2AR level without altering adenosine A1 receptors level; and the agonist of A2AR (CGS 21680) rather than antagonist (SCH 58261) could reverse the potentiation of behavioral-LTP induced by cordycepin. These results suggested that cordycepin improved behavioral-LTP and morphological structure of dendrite in hippocampal CA1 but did not contribute to the improvement of learning and memory. And cordycepin improved behavioral-LTP may be through reducing the level of A2AR in hippocampus. Collectively, the effects of cordycepin on cognitive function and LTP were complex and involved multiple mechanisms.
蛹虫草素是一种腺嘌呤类似物，据报道可改善认知功能，但这似乎与蛹虫草素抑制长时程增强（LTP）的报道不一致。行为性-LTP 通常用于研究自由活动动物学习任务诱导的长时程突触可塑性。为了研究蛹虫草素对大鼠 LTP 和行为的同时影响，我们通过在海马 CA1 区记录群体锋电位，应用 Y 迷宫学习任务诱导的行为性-LTP 模型。高尔基染色和邵氏分析用于评估海马 CA1 区锥体神经元树突的形态结构，Western blot 用于检测腺苷 A1 受体和 A2A 受体（A2AR）的水平。我们发现蛹虫草素显著提高了行为性-LTP 的幅度，伴随着树突总长度、交点数量和棘突密度的增加，但不影响 Y 迷宫学习任务。此外，蛹虫草素明显降低了 A2AR 水平而不改变腺苷 A1 受体水平；A2AR 的激动剂（CGS 21680）而不是拮抗剂（SCH 58261）可以逆转蛹虫草素引起的行为性-LTP 的增强。这些结果表明，蛹虫草素改善了海马 CA1 的行为性-LTP 和树突形态结构，但对学习和记忆的改善没有贡献。而蛹虫草素改善行为性-LTP 可能是通过降低海马中的 A2AR 水平。总之，蛹虫草素对认知功能和 LTP 的影响是复杂的，涉及多种机制。
