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Modulation of presynaptic glucocorticoid receptors on glutamate release from rat hippocampal nerve terminals
Author(s) -
Wang ChiaChuan,
Wang SuJane
Publication year - 2009
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20654
Subject(s) - glutamate receptor , hippocampal formation , corticosterone , hippocampus , endocrinology , medicine , glucocorticoid receptor , antiglucocorticoid , synaptosome , antagonist , nmda receptor , systemic administration , chemistry , 4 aminopyridine , glucocorticoid , receptor , biology , central nervous system , potassium channel , microbiology and biotechnology , hormone , in vivo
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. Synapse 63:745–751, 2009. © 2009 Wiley‐Liss, Inc.