{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T14:18:50Z","timestamp":1775744330229,"version":"3.50.1"},"reference-count":50,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,11,3]],"date-time":"2018-11-03T00:00:00Z","timestamp":1541203200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004319","name":"Shin Kong Wu Ho-Su Memorial Hospital","doi-asserted-by":"publisher","award":["106-SKH-FJH-03"],"award-info":[{"award-number":["106-SKH-FJH-03"]}],"id":[{"id":"10.13039\/501100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Synapse"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Allopregnanolone, an active metabolite of progesterone, has been reported to exhibit neuroprotective activity in several preclinical models. Considering that the excitotoxicity caused by excessive glutamate is implicated in many brain disorders, the effect of allopregnanolone on glutamate release in rat cerebrocortical nerve terminals and possible underlying mechanism were investigated. We observed that allopregnanolone inhibited 4\u2010aminopyridine (4\u2010AP)\u2010evoked glutamate release, and this inhibition was prevented by chelating the extracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ions and the vesicular transporter inhibitor. Allopregnanolone reduced the elevation of 4\u2010AP\u2010evoked intrasynaptosomal Ca\n                    <jats:sup>2+<\/jats:sup>\n                    levels, but did not affect the synaptosomal membrane potential. In the presence of N\u2010, P\/Q\u2010, and R\u2010type channel blockers, allopregnanolone\u2010mediated inhibition of 4\u2010AP\u2010evoked glutamate release was markedly reduced; however, the intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010release inhibitors did not affect the allopregnanolone effect. Furthermore, allopregnanolone\u2010mediated inhibition of 4\u2010AP\u2010evoked glutamate release was completely abolished in the synaptosomes pretreated with inhibitors of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    \/calmodulin, adenylate cyclase, and protein kinase A (PKA), namely calmidazolium, MDL12330A, and H89, respectively. Additionally, the allopregnanolone effect on evoked glutamate release was antagonized by the GABA\n                    <jats:sub>A<\/jats:sub>\n                    receptor antagonist SR95531. Our data are the first to suggest that allopregnanolone reduce the Ca\n                    <jats:sup>2+<\/jats:sup>\n                    influx through N\u2010, P\/Q\u2010, and R\u2010type Ca\n                    <jats:sup>2+<\/jats:sup>\n                    channels, through the activation of GABA\n                    <jats:sub>A<\/jats:sub>\n                    receptors present on cerebrocortical nerve terminals, subsequently suppressing the Ca\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010calmodulin\/PKA cascade and decreasing 4\u2010AP\u2010evoked glutamate release.\n                  <\/jats:p>","DOI":"10.1002\/syn.22076","type":"journal-article","created":{"date-parts":[[2018,10,26]],"date-time":"2018-10-26T01:24:32Z","timestamp":1540517072000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Neurosteroid allopregnanolone inhibits glutamate release from rat cerebrocortical nerve terminals"],"prefix":"10.1002","volume":"73","author":[{"given":"Yi","family":"Chang","sequence":"first","affiliation":[{"name":"Department of Anesthesiology Shin Kong Wu Ho\u2010Su Memorial Hospital Taipei Taiwan"},{"name":"School of Medicine Fu Jen Catholic University New Taipei City Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsi Lung","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Department of Nursing, Division of Basic Medical Sciences, Research Center for Chinese Herbal Medicine, and Graduate Institute of Health Industry Technology Chang Gung University of Science and Technology Tao\u2010Yuan Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shu Kuei","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Far\u2010Eastern Memorial Hospital New Taipei City 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