{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,3]],"date-time":"2025-05-03T22:10:10Z","timestamp":1746310210360,"version":"3.40.4"},"reference-count":44,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2014,7,18]],"date-time":"2014-07-18T00:00:00Z","timestamp":1405641600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>Our previous studies indicate that glycine can inhibit N\u2010methyl\u2010D\u2010aspartate receptor (<jats:styled-content style=\"fixed-case\">NMDAR<\/jats:styled-content>) responses induced by high concentrations of<jats:styled-content style=\"fixed-case\">NMDA<\/jats:styled-content>in rat hippocampal neurons. The present study was designed to observe whether D\u2010serine induces inactivation of<jats:styled-content style=\"fixed-case\">NMDAR<\/jats:styled-content>s in cultured rat hippocampal neurons and to investigate the underlying mechanisms of this effect.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Cell culture, whole\u2010cell patch\u2010clamp electrophysiology, Ca<jats:sup>2+<\/jats:sup>imaging, immunohistochemistry, and Western blot analysis were used.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that the peak current and Ca<jats:sup>2+<\/jats:sup>influx evoked by 30\u00a0<jats:italic>\u03bc<\/jats:italic>M NMDA were increased by co\u2010application of D\u2010serine, but those evoked by 300\u00a0<jats:italic>\u03bc<\/jats:italic>M NMDA were reduced dose\u2010dependently by co\u2010application of D\u2010serine. However, the inhibitory effect of D\u2010serine on NMDAR responses was reversed by ZnCl<jats:sub>2<\/jats:sub>(30\u00a0nM), an inhibitor of the NR2A subunit, but was less influenced by ifenprodil (10\u00a0<jats:italic>\u03bc<\/jats:italic>M), an NR2B inhibitor. In addition, the inhibitory effect of D\u2010serine was not detected in young hippocampal neurons that expressed less of the NR2A subunits and reversed in the presence of 10\u00a0mM BAPTA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>D\u2010Serine can also induce inactivation of<jats:styled-content style=\"fixed-case\">NMDAR<\/jats:styled-content>s, the<jats:styled-content style=\"fixed-case\">NR<\/jats:styled-content>2A subunit is required for the induction of this effect, and this inactivation is Ca<jats:sup>2+<\/jats:sup>\u2010dependent in nature. This action of D\u2010serine is hypothesized to play a neuroprotective role upon a sustained large glutamate insult to the brain.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.12308","type":"journal-article","created":{"date-parts":[[2014,7,18]],"date-time":"2014-07-18T11:25:03Z","timestamp":1405682703000},"page":"951-960","source":"Crossref","is-referenced-by-count":3,"title":["D\u2010Serine\u2010induced Inactivation of<scp>NMDA<\/scp>Receptors in Cultured Rat Hippocampal Neurons Expressing<scp>NR<\/scp>2A Subunits is Ca<sup>2+<\/sup>\u2010Dependent"],"prefix":"10.1111","volume":"20","author":[{"given":"Xia","family":"Li","sequence":"first","affiliation":[{"name":"Department of Neuropharmacology Institute of Nautical Medicine Nantong University Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan\u2010Yuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology Affiliated Hospital Nantong University Jiangsu 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