{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T07:02:10Z","timestamp":1790233330379,"version":"4.1.0"},"reference-count":38,"publisher":"National Academy of Sciences","issue":"12","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2011,3,22]]},"abstract":"\n Ethanol exposure during developmental synaptogenesis can lead to brain defects referred to as fetal alcohol syndrome (FAS), which can include mental health problems such as cognitive deficits and mental retardation. In FAS, widespread neuronal death and brain mass loss precedes behavioral and cognitive impairments in adulthood. Because tissue plasminogen activator (tPA) has been implicated in neurodegeneration, we examined whether it mediates FAS. Neonatal WT and tPA\n \u2212\/\u2212<\/jats:sup>\n mice were injected with ethanol to mimic FAS in humans. In WT mice, ethanol elicited caspase-3 activation, significant forebrain neurodegeneration, and decreased contextual fear conditioning in adults. However, tPA-deficient mice were protected from these neurotoxicities, and this protection could be abrogated by exogenous tPA. Selective pharmacological modulators of NMDA and GABA\n A<\/jats:sub>\n receptor pathways revealed that the effects of tPA were mediated by the NR2B subunit of the NMDA receptor. This study identifies tPA as a critical signaling component in FAS.\n <\/jats:p>","DOI":"10.1073\/pnas.1017608108","type":"journal-article","created":{"date-parts":[[2011,3,8]],"date-time":"2011-03-08T07:01:21Z","timestamp":1299567681000},"page":"5069-5074","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":43,"title":["Tissue plasminogen activator is required for the development of fetal alcohol syndrome in mice"],"prefix":"10.1073","volume":"108","author":[{"given":"Melissa","family":"Noel","sequence":"first","affiliation":[{"name":"Laboratory of Neurobiology and Genetics, The Rockefeller University, New York, NY 10065"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin H.","family":"Norris","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology and Genetics, The Rockefeller University, New York, NY 10065"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sidney","family":"Strickland","sequence":"additional","affiliation":[{"name":"Laboratory of Neurobiology and Genetics, The Rockefeller University, New York, NY 10065"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2011,3,7]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.155.4.552"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.287.5455.1056"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.283.5398.70"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2467382"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0028-3908(94)00155-L"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1006\/nbdi.2001.0411"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2002.tb00467.x"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80597-8"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0705848104"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/361453a0"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80483-3"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/377340a0"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0406454102"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401277"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2001.tb02260.x"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2004.08.006"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e3181a9d524"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1009685428847"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.120.2.503"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/384123b0"},{"key":"e_1_3_3_21_2","first-page":"227","article-title":"Studies of the ultrastructure and permeability of the blood-brain barrier in the developing corpus callosum in postnatal rat brain using electron dense tracers","volume":"184","author":"Xu J","year":"1994","unstructured":"J Xu, EA Ling, Studies of the ultrastructure and permeability of the blood-brain barrier in the developing corpus callosum in postnatal rat brain using electron dense tracers. J Anat 184, 227\u2013237 (1994).","journal-title":"J Anat"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200806024"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20070304"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(87)90505-2"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.78.11.7180"},{"key":"e_1_3_3_26_2","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1016\/S0022-3565(24)37138-1","article-title":"Ro 25-6981, a highly potent and selective blocker of N-methyl-d-aspartate receptors containing the NR2B subunit. Characterization in vitro","volume":"283","author":"Fischer G","year":"1997","unstructured":"G Fischer, et al., Ro 25-6981, a highly potent and selective blocker of N-methyl-d-aspartate receptors containing the NR2B subunit. Characterization in vitro. J Pharmacol Exp Ther 283, 1285\u20131292 (1997).","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0708823105"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.99.2.232"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2007-1399"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.1996.tb01951.x"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1006\/nimg.2001.0977"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1477"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0711568105"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1037\/0735-7044.110.5.1177"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.16-07-02220.1996"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.170.3962.1095"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-06-02125.2002"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(00)02513-0"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1017608108","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T15:38:34Z","timestamp":1741016314000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1017608108"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,3,7]]},"references-count":38,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2011,3,22]]}},"alternative-id":["10.1073\/pnas.1017608108"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1017608108","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,3,7]]},"assertion":[{"value":"2011-03-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}