title: Effects of ethanol exposure in utero on Cajal-Retzius cells in the developing cortex.
abstract: BACKGROUND
  Prenatal exposure to ethanol exerts teratogenic effects on the developing brain. Here, we tested the hypothesis that exposure to ethanol in utero alters the disposition of Cajal-Retzius cells that play a key role in orchestrating proliferation, migration, and laminar integration of cortical neurons in the embryonic cortex.
  
  
  METHODS
  Pregnant Ebf2-EGFP mice, harboring EGFP-fluorescent Cajal-Retzius cells, were subjected to a 2% w/w ethanol consumption regimen starting at neural tube closure and lasting throughout gestation. Genesis of Cajal-Retzius cells was assessed by means of 5-bromo-2-deoxyuridine (BrdU) immunofluorescence at embryonic day 12.5, their counts and distribution were determined between postnatal day (P)0 and P4, patch clamp electrophysiology was performed between P2 and P3 to analyze GABA-mediated synaptic activity, and open-field behavioral testing was conducted in P45-P50 adolescents.
  
  
  RESULTS
  In Ebf2-EGFP embryos exposed to ethanol in utero, we found increased BrdU labeling and expanded distribution of Cajal-Retzius cells in the cortical hem, pointing to increased genesis and proliferation. Postnatally, we found an increase in Cajal-Retzius cell number in cortical layer I. In addition, they displayed altered patterning of spontaneous GABA-mediated synaptic barrages and enhanced GABA-mediated synaptic activity, suggesting enhanced GABAergic tone.
  
  
  CONCLUSIONS
  These findings, together, underscore that Cajal-Retzius cells contribute to the ethanol-induced aberration of cortical development and abnormal GABAergic neurotransmission at the impactful time when intracortical circuits form.
authors.affiliation: Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire.
authors.forename: Alexander G J
authors.initials: AG
authors.lastname: Skorput
authors.forename: Hermes H
authors.initials: HH
authors.lastname: Yeh
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology* / Q000503:physiopathology; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D059330:GABAergic Neurons / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D055369:Miniature Postsynaptic Potentials / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D055495:Neurogenesis / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D000091042:Reelin Protein
chemical_list: D000091042:Reelin Protein; D000431:Ethanol; C000717128:Reln protein, mouse
keywords: BrdU; Cortical Development; GABA; GABA-Mediated Synaptic Activity; Reelin
references.citation: Alcohol Clin Exp Res. 2006 Feb;30(2):222-32
references.pmid: 16441271
references.citation: J Neurosci. 2008 Feb 20;28(8):1854-64
references.pmid: 18287502
references.citation: J Neurocytol. 1983 Oct;12(5):863-71
references.pmid: 6644358
references.citation: Nat Genet. 1995 May;10(1):77-83
references.pmid: 7647795
references.citation: J Neurosci. 2000 Aug 1;20(15):5764-74
references.pmid: 10908617
references.citation: J Neurosci. 2002 Aug 15;22(16):6908-19
references.pmid: 12177189
references.citation: J Neurosci. 1999 Dec 15;19(24):10856-68
references.pmid: 10594067
references.citation: Neuron. 1995 Dec;15(6):1287-98
references.pmid: 8845153
references.citation: Curr Opin Neurobiol. 1998 Oct;8(5):570-5
references.pmid: 9811621
references.citation: Nat Neurosci. 2011 Jun;14(6):697-703
references.pmid: 21516100
references.citation: Nat Rev Mol Cell Biol. 2005 Oct;6(10):777-88
references.pmid: 16314867
references.citation: Nature. 2003 Oct 30;425(6961):917-25
references.pmid: 14586460
references.citation: Brain Sci. 2013 Apr 29;3(2):704-27
references.pmid: 24027632
references.citation: J Comp Neurol. 2007 Jan 20;500(3):419-32
references.pmid: 17120279
references.citation: Neurochem Res. 2014 Jun;39(6):1162-70
references.pmid: 24710789
references.citation: J Neurochem. 1998 Mar;70(3):1160-6
references.pmid: 9489737
references.citation: J Anat. 2010 Oct;217(4):334-43
references.pmid: 20626498
references.citation: Int J Environ Res Public Health. 2010 Feb;7(2):364-79
references.pmid: 20616979
references.citation: Front Neuroanat. 2010 Mar 03;4:10
references.pmid: 20339484
references.citation: J Comp Neurol. 1990 Sep 1;299(1):89-105
references.pmid: 2212113
references.citation: Neural Dev. 2008;3:30
references.pmid: 18986511
references.citation: Nat Neurosci. 2003 Dec;6(12):1284-91
references.pmid: 14608361
references.citation: Nat Neurosci. 2005 Aug;8(8):1002-12
references.pmid: 16041369
references.citation: J Neurosci. 2006 Feb 8;26(6):1767-75
references.pmid: 16467525
references.citation: J Physiol. 1998 Nov 1;512 ( Pt 3):809-17
references.pmid: 9769423
references.citation: Neuron. 1995 May;14(5):899-912
references.pmid: 7748558
references.citation: J Physiol. 2009 May 1;587(Pt 9):1881-8
references.pmid: 19188247
references.citation: Neuroreport. 2011 Aug 3;22(11):525-9
references.pmid: 21666518
references.citation: J Neurosci. 2013 Nov 27;33(48):18893-905
references.pmid: 24285895
references.citation: Neuron. 2011 Feb 10;69(3):482-97
references.pmid: 21315259
references.citation: J Neurosci. 2008 May 21;28(21):5547-58
references.pmid: 18495889
references.citation: J Atten Disord. 2006 Feb;9(3):515-22
references.pmid: 16481668
references.citation: Neuron. 2013 Aug 7;79(3):461-77
references.pmid: 23931996
references.citation: Neuron. 1998 Mar;20(3):541-52
references.pmid: 9539127
references.citation: Neuron. 2005 May 5;46(3):389-94
references.pmid: 15882637
references.citation: Pharmacol Ther. 2005 Jul;107(1):80-98
references.pmid: 15963352
references.citation: Nature. 1995 Apr 20;374(6524):719-23
references.pmid: 7715726
references.citation: J Neurosci. 2007 Nov 7;27(45):12367-77
references.pmid: 17989301
references.citation: Brain Res. 2008 Nov 6;1239:85-91
references.pmid: 18789906
references.citation: Cereb Cortex. 2000 Jun;10(6):602-13
references.pmid: 10859138
references.citation: Neuroscience. 1990;36(3):839-56
references.pmid: 2234416
references.citation: Neuroscience. 2012 Oct 11;222:417-28
references.pmid: 22742906
references.citation: Cereb Cortex. 1999 Dec;9(8):765-75
references.pmid: 10600995
references.citation: J Am Acad Child Adolesc Psychiatry. 1993 Sep;32(5):990-4
references.pmid: 8407775
references.citation: Development. 2011 Dec;138(23):5223-34
references.pmid: 22069190
references.citation: J Neurosci. 2011 Jun 22;31(25):9426-39
references.pmid: 21697392
references.citation: J Neurosci. 2003 Jul 16;23(15):6272-9
references.pmid: 12867512
references.citation: Neuroscience. 1992 Jul;49(1):13-32
references.pmid: 1357584