Wang Chia-Chuan, Wang Su-Jane
Fu Jen Catholic University, Hsin-Chuang, Taipei County, Taiwan.
Synapse. 2009 Sep;63(9):745-51. doi: 10.1002/syn.20654.
In this study, we have examined the role of corticosterone (CORT) in the regulation of neuronal glutamate release using nerve terminals (synaptosomes) isolated from the rat hippocampus. Adult male Sprague-Dawley rats received either a chronic systemic administration of CORT (daily 25 mg/kg in sesame oil, subcutaneously) or long-term bilateral adrenalectomy (ADX) (3-4 weeks), and then the release of 4-aminopyridine (4AP)-evoked endogenous glutamate and the levels of glucocorticoid receptor (GR) expression from hippocampal nerve terminals were studied. Chronic administration of CORT resulted in a significant increase of 4AP-evoked glutamate release from hippocampal nerve terminals, whereas ADX reduced 4AP-evoked glutamate release. In addition, chronic administration of CORT and ADX induced a significant reduction and increase in GR expression in hippocampal synaptosomes, respectively, as detected by Western blots. Furthermore, acute treatment of CORT or dexamethasone facilitated 4AP-evoked glutamate release from synaptosomes freshly isolated from naïve rat hippocampus and this effect can be significantly prevented by pretreatment of GR antagonist mifepristone, but not by mineralocorticoid receptor (MR) antagonist RU28318. Together, our results strongly support the presence of GRs on presynaptic nerve terminals in the rat hippocampus acting to facilitate the release of neuronal glutamate.
在本研究中，我们使用从大鼠海马体分离的神经末梢（突触体），研究了皮质酮（CORT）在调节神经元谷氨酸释放中的作用。成年雄性Sprague-Dawley大鼠接受了CORT的慢性全身给药（每天25mg/kg芝麻油，皮下注射）或长期双侧肾上腺切除术（ADX）（3 - 4周），然后研究了4-氨基吡啶（4AP）诱发的内源性谷氨酸释放以及海马神经末梢糖皮质激素受体（GR）的表达水平。慢性给予CORT导致海马神经末梢4AP诱发的谷氨酸释放显著增加，而ADX则降低了4AP诱发的谷氨酸释放。此外，通过蛋白质免疫印迹法检测发现，慢性给予CORT和ADX分别导致海马突触体中GR表达显著降低和增加。此外，急性给予CORT或地塞米松促进了从未处理的大鼠海马体新鲜分离的突触体中4AP诱发的谷氨酸释放，并且这种作用可被GR拮抗剂米非司酮预处理显著阻断，但不能被盐皮质激素受体（MR）拮抗剂RU28318阻断。总之，我们的结果有力地支持了大鼠海马体突触前神经末梢存在GRs，其作用是促进神经元谷氨酸的释放。
