{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T06:45:55Z","timestamp":1790145955014,"version":"4.0.1"},"reference-count":61,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2018,7,16]],"date-time":"2018-07-16T00:00:00Z","timestamp":1531699200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AA015747"],"award-info":[{"award-number":["AA015747"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008893","name":"University of Iowa","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008893","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alcoholism Clin &amp;amp; Exp Res"],"published-print":{"date-parts":[[2018,9]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Alcohol exposure during pregnancy can kill developing neurons and lead to fetal alcohol spectrum disorder (FASD). However, affected individuals differ in their regional patterns of alcohol\u2010induced neuropathology. Because neuroprotective genes are expressed in spatially selective ways, their mutation could increase the vulnerability of some brain regions, but not others, to alcohol teratogenicity. The objective of this study was to determine whether a null mutation of neuronal nitric oxide synthase (nNOS) can increase the vulnerability of some brain regions, but not others, to alcohol\u2010induced neuronal losses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Immunohistochemistry identified brain regions in which nNOS is present or absent throughout postnatal development. Mice genetically deficient for nNOS (nNOS<jats:sup>\u2212\/\u2212<\/jats:sup>) and wild\u2010type controls received alcohol (0.0, 2.2, or 4.4\u00a0mg\/g\/d) over postnatal days (PD) 4 to 9. Mice were sacrificed in adulthood (~PD 115), and surviving neurons in the olfactory bulb granular layer and brain stem facial nucleus were quantified stereologically.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>nNOS was expressed throughout postnatal development in olfactory bulb granule cells but was never expressed in the facial nucleus. In wild\u2010type mice, alcohol reduced neuronal survival to similar degrees in both cell populations. However, null mutation of nNOS more than doubled alcohol\u2010induced cell death in the olfactory bulb granule cells, while the mutation had no effect on the facial nucleus neurons. As a result, in nNOS<jats:sup>\u2212\/\u2212<\/jats:sup> mice, alcohol caused substantially more cell loss in the olfactory bulb than in the facial nucleus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Mutation of the nNOS gene substantially increases vulnerability to alcohol\u2010induced cell loss in a brain region where the gene is expressed (olfactory bulb), but not in a separate brain region, where the gene is not expressed (facial nucleus). Thus, differences in genotype may explain why some individuals are vulnerable to FASD, while others are not, and may determine the specific patterns of neuropathology in children with FASD.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.13824","type":"journal-article","created":{"date-parts":[[2018,6,29]],"date-time":"2018-06-29T13:21:54Z","timestamp":1530278514000},"page":"1627-1639","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Regional Patterns of Alcohol\u2010Induced Neuronal Loss Depend on Genetics: Implications for Fetal Alcohol Spectrum Disorder"],"prefix":"10.1111","volume":"42","author":[{"given":"Dylan","family":"Todd","sequence":"first","affiliation":[{"name":"Neuroscience Program  Carver College of Medicine University of Iowa Iowa City Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Daniel J.","family":"Bonthius","sequence":"additional","affiliation":[{"name":"Department of Biology  Wartburg College Waverly Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lia Marie","family":"Sabalo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics  Carver College of Medicine University of Iowa Iowa City Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmine","family":"Roghair","sequence":"additional","affiliation":[{"name":"Department of Pediatrics  Carver College of Medicine University of Iowa Iowa City Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bahri","family":"Karacay","sequence":"additional","affiliation":[{"name":"Department of Pediatrics  Carver College of Medicine University of Iowa Iowa City Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha Larimer","family":"Bousquet","sequence":"additional","affiliation":[{"name":"Department of Biology  Wartburg College Waverly Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7570-3796","authenticated-orcid":false,"given":"Daniel J.","family":"Bonthius","sequence":"additional","affiliation":[{"name":"Neuroscience Program  Carver College of Medicine University of Iowa Iowa City Iowa"},{"name":"Department of Pediatrics  Carver College of Medicine University of Iowa Iowa City Iowa"},{"name":"Department of Neurology  Carver College of Medicine University of Iowa Iowa City Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,7,16]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2008.08.007"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ntt.2003.08.004"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-3806(02)00549-7"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.21095"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresprot.2004.09.003"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-3806(02)00458-3"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.1990.tb00455.x"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2014.11.009"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2016.09.012"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.vh.2016.10.008"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(75)80919-X"},{"key":"e_1_2_7_13_1","first-page":"363","article-title":"Genetic evidence for the neuronal neuronal nitric oxide synthase gene (NOS1) as a susceptibility locus for infantile pyloric stenosis","volume":"58","author":"Chung E","year":"1996","journal-title":"Am J Hum Genet"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.midw.2017.04.011"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10995-015-1779-x"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.16-08-02479.1996"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2009.01.010"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/0378-3782(79)90022-7"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1017\/neu.2015.12"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/acer.13066"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3350527"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu469"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/acprof:oso\/9780195183139.003.0009"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1177\/1073858417697037"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/acer.13366"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2014.00203"},{"key":"e_1_2_7_27_1","first-page":"59","volume-title":"Alcohol: Effects on Brain and Development","author":"Goodlett CR","year":"1999"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/jemt.20219"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2818.1986.tb02764.x"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2818.1987.tb02837.x"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/neu.20208"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2015-4256"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90615-W"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6123(08)63197-0"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2014.10.014"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/nlx064"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.10251"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-015-0155-0"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2007.01.059"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/acer.12615"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2002.tb02455.x"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2004.07.047"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg009"},{"key":"e_1_2_7_44_1","first-page":"159","article-title":"Effects of alcohol on the fetus: impact and prevention","volume":"125","author":"Little RE","year":"1981","journal-title":"Can Med Assoc J"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11065-011-9167-9"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.094938"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2011.01441.x"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mri.2017.06.012"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1017608108"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-3806(98)00107-2"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.15288\/jsad.2014.75.937"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/0887-8994(94)90012-4"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-3806(98)00140-0"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpedsurg.2011.05.021"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.alcohol.2009.08.008"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.290.22.2996"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320470612"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1111\/acer.12286"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20125"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(88)91114-6"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1002\/ar.a.20271"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2016.03.023"}],"container-title":["Alcoholism: Clinical and Experimental Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Facer.13824","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acer.13824","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,17]],"date-time":"2023-09-17T22:35:54Z","timestamp":1694990154000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acer.13824"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,7,16]]},"references-count":61,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2018,9]]}},"alternative-id":["10.1111\/acer.13824"],"URL":"https:\/\/doi.org\/10.1111\/acer.13824","archive":["Portico"],"relation":{},"ISSN":["0145-6008","1530-0277"],"issn-type":[{"value":"0145-6008","type":"print"},{"value":"1530-0277","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,7,16]]},"assertion":[{"value":"2017-12-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-06-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-07-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}