{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T12:33:42Z","timestamp":1774355622765,"version":"3.50.1"},"reference-count":53,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2016,4,3]],"date-time":"2016-04-03T00:00:00Z","timestamp":1459641600000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003056","name":"Ente Cassa di Risparmio di Firenze","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003056","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Alcoholism Clin &amp;amp; Exp Res"],"published-print":{"date-parts":[[2016,4]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The developing brain is particularly vulnerable to alcohol: Drinking during pregnancy can lead to a number of physical, learning, and behavioral disorders in the newborn. It has been demonstrated that immature and mature brain tissues display a differential sensitivity to ethanol (EtOH) toxicity and that cerebral structure and function are diversely impaired according to the stage of synaptic maturation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Rat organotypic hippocampal slice cultures were exposed for 7\u00a0days to EtOH (100 to 300\u00a0mM) after 2 days (immature) or 10\u00a0days (mature) of culture in\u00a0vitro; EtOH was then removed from the medium, and 24\u00a0hours later, slices were analyzed by fluorescence microscopy, Western blotting, electrophysiology, and electron microscopy to explore the molecular mechanisms of EtOH toxicity in the developing hippocampus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>EtOH withdrawal elicited a selective <jats:styled-content style=\"fixed-case\">CA<\/jats:styled-content>1 pyramidal cell injury in mature slices, but not in immature slices. A significant increase in the expression of pre\u2010 and postsynaptic proteins in mature slices revealed that slice maturation is presumably associated with the development of new synapses. Incubation with chronic EtOH for 7\u00a0days and its removal from the medium induced a significant decrease in GluA1 and GluA2 expression levels; a significant reduction in the expression of synaptophysin and GluN2A was observed only after EtOH withdrawal. Whole\u2010cell patch\u2010clamp recordings showed that incubation with EtOH for 7\u00a0days induced a significant decrease in <jats:styled-content style=\"fixed-case\">spontaneous excitatory postsynaptic current (sEPSC)<\/jats:styled-content> frequency in <jats:styled-content style=\"fixed-case\">CA<\/jats:styled-content>1 pyramidal cells of immature slices and a trend toward a decrease in <jats:styled-content style=\"fixed-case\">sEPSC<\/jats:styled-content> amplitude. Electron microscopy revealed a disorganization of neurotubuli in immature slices after chronic exposure to EtOH.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These results indicate that prolonged incubation with EtOH and its subsequent withdrawal from the medium induce an impairment of excitatory synaptic transmission and possibly an incorrect formation of neuronal circuits in developing hippocampus in\u00a0vitro, which is suggestive of mechanisms that may lead to mental retardation in fetal alcohol spectrum disorders.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.13006","type":"journal-article","created":{"date-parts":[[2016,4,3]],"date-time":"2016-04-03T22:27:20Z","timestamp":1459722440000},"page":"706-716","source":"Crossref","is-referenced-by-count":22,"title":["Ethanol Toxicity During Brain Development: Alterations of Excitatory Synaptic Transmission in Immature Organotypic Hippocampal Slice 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