{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T16:42:48Z","timestamp":1792082568012,"version":"4.4.0"},"reference-count":81,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2001,11,30]],"date-time":"2001-11-30T00:00:00Z","timestamp":1007078400000},"content-version":"vor","delay-in-days":333,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Ment. Retard. Dev. Disabil. Res. Rev."],"published-print":{"date-parts":[[2001,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>It has been known for three decades that ethanol, the most widely abused drug in the world, has deleterious effects on the developing human brain, but progress has been slow in developing animal models that are optimal for studying this problem, and the underlying mechanisms have remained elusive. Recently, we have shown that during the synaptogenesis period, also known as the brain growth spurt period, ethanol has the potential to trigger widespread neuronal suicide (apoptosis), deleting many millions of neurons from the in vivo mammalian brain. It appears that ethanol triggers apoptotic neurodegeneration by a dual mechanism (blockade of NMDA glutamate receptors and excessive activation of GABA<jats:sub>A<\/jats:sub> receptors), in that ethanol has both NMDA antagonist and GABAmimetic properties; we have shown that other drugs which have either of these properties trigger apoptotic neurodegeneration in the developing brain. The brain growth spurt period in humans spans the last trimester of pregnancy and the first several years after birth. Thus, our findings provide a likely explanation for the reduced brain mass and neurobehavioral disturbances associated with the human fetal alcohol syndrome. Furthermore, since NMDA antagonist and GABAmimetic drugs are sometimes abused by pregnant women and also are used as anticonvulsants, sedatives, or anesthetics in pediatric medicine, our findings suggest the possibility that exposure of the developing brain to these various drugs either pre or postnatally could contribute to mental disability syndromes that have heretofore been attributed to unknown causes. In addition, the observation that ethanol and related drugs trigger massive neuronal apoptosis in the developing brain provides an unprecedented opportunity to study both neuropathological aspects and molecular mechanisms of apoptotic neurodegeneration in the in vivo mammalian brain. MRDD Research Reviews 2001;7:267\u2013275. \u00a9 2001 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/mrdd.1037","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T16:25:38Z","timestamp":1030292738000},"page":"267-275","source":"Crossref","is-referenced-by-count":59,"title":["Glutamate signaling and the fetal alcohol 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