PMID- 21074610 OWN - NLM STAT- MEDLINE DCOM- 20110722 LR - 20211020 IS - 1872-9738 (Electronic) IS - 0892-0362 (Print) IS - 0892-0362 (Linking) VI - 33 IP - 2 DP - 2011 Mar-Apr TI - Ventromedian forebrain dysgenesis follows early prenatal ethanol exposure in mice. PG - 231-9 LID - 10.1016/j.ntt.2010.11.001 [doi] AB - Ethanol exposure on gestational day (GD) 7 in the mouse has previously been shown to result in ventromedian forebrain deficits along with facial anomalies characteristic of fetal alcohol syndrome (FAS). To further explore ethanol's teratogenic effect on the ventromedian forebrain in this mouse model, scanning electron microscopic and histological analyses were conducted. For this, time mated C57Bl/6J mice were injected with 2.9g/kg ethanol or saline twice, at a 4h interval, on their 7th day of pregnancy. On GD 12.5, 13 and 17, control and ethanol-exposed specimens were collected and processed for light and scanning electron microscopic analyses. Gross morphological changes present in the forebrains of ethanol-exposed embryos included cerebral hemispheres that were too close in proximity or rostrally united, enlarged foramina of Monro, enlarged or united lateral ventricles, and varying degrees of hippocampal and ventromedian forebrain deficiency. In GD 12.5 control and ethanol-exposed embryos, in situ hybridization employing probes for Nkx2.1 or Fzd8 to distinguish the preoptic area and medial ganglionic eminences (MGEs) from the lateral ganglionic eminences, respectively, confirmed the selective loss of ventromedian tissues. Immunohistochemical labeling of oligodendrocyte progenitors with Olig2, a transcription factor necessary for their specification, and of GABA, an inhibitory neurotransmitter, showed ethanol-induced reductions in both. To investigate later consequences of ventromedian forebrain loss, MGE-derived somatostatin-expressing interneurons in the subpallial region of GD 17 fetal mice were examined, with results showing that the somatostatin-expressing interneurons that were present were dysmorphic in the ethanol-exposed fetuses. The potential functional consequences of this insult are discussed. CI - Copyright (c) 2010 Elsevier Inc. All rights reserved. FAU - Godin, Elizabeth A AU - Godin EA AD - Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, NC 27599-7178, USA. FAU - Dehart, Deborah B AU - Dehart DB FAU - Parnell, Scott E AU - Parnell SE FAU - O'Leary-Moore, Shonagh K AU - O'Leary-Moore SK FAU - Sulik, Kathleen K AU - Sulik KK LA - eng GR - U01 AA017124-05/AA/NIAAA NIH HHS/United States GR - AA007573/AA/NIAAA NIH HHS/United States GR - P60 AA011605-14/AA/NIAAA NIH HHS/United States GR - P60 AA011605/AA/NIAAA NIH HHS/United States GR - AA011605/AA/NIAAA NIH HHS/United States GR - P50 AA011605/AA/NIAAA NIH HHS/United States GR - AA017124/AA/NIAAA NIH HHS/United States GR - T32 AA007573-14/AA/NIAAA NIH HHS/United States GR - U01 AA017124/AA/NIAAA NIH HHS/United States GR - T32 AA007573/AA/NIAAA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20101111 PL - United States TA - Neurotoxicol Teratol JT - Neurotoxicology and teratology JID - 8709538 RN - 0 (Nkx2-1 protein, mouse) RN - 0 (Nuclear Proteins) RN - 0 (Receptors, G-Protein-Coupled) RN - 0 (Teratogens) RN - 0 (Thyroid Nuclear Factor 1) RN - 0 (Transcription Factors) RN - 0 (frizzled 8 protein, mouse) RN - 3K9958V90M (Ethanol) SB - IM MH - Abnormalities, Drug-Induced/embryology/*etiology/metabolism/pathology MH - Animals MH - Ethanol/*toxicity MH - Female MH - Gestational Age MH - Immunohistochemistry MH - In Situ Hybridization MH - Mice MH - Mice, Inbred C57BL MH - Microscopy, Electron, Scanning MH - Nuclear Proteins/metabolism MH - Pregnancy MH - Prenatal Exposure Delayed Effects/*chemically induced/metabolism/pathology MH - Receptors, G-Protein-Coupled/metabolism MH - Teratogens/*toxicity MH - Thyroid Nuclear Factor 1 MH - Transcription Factors/metabolism MH - Ventromedial Hypothalamic Nucleus/*abnormalities/embryology/metabolism/ultrastructure PMC - PMC3070193 MID - NIHMS253400 EDAT- 2010/11/16 06:00 MHDA- 2011/07/23 06:00 PMCR- 2012/03/01 CRDT- 2010/11/16 06:00 PHST- 2010/09/08 00:00 [received] PHST- 2010/11/07 00:00 [accepted] PHST- 2010/11/16 06:00 [entrez] PHST- 2010/11/16 06:00 [pubmed] PHST- 2011/07/23 06:00 [medline] PHST- 2012/03/01 00:00 [pmc-release] AID - S0892-0362(10)00195-9 [pii] AID - 10.1016/j.ntt.2010.11.001 [doi] PST - ppublish SO - Neurotoxicol Teratol. 2011 Mar-Apr;33(2):231-9. doi: 10.1016/j.ntt.2010.11.001. Epub 2010 Nov 11.