title: Ethanol induces cytostasis of cortical basal progenitors.
abstract: BACKGROUND
  Developing brain is a major target for alcohol's actions and neurological/functional abnormalities include microencephaly, reduced frontal cortex, mental retardation and attention-deficits. Previous studies have shown that ethanol altered the lateral ventricular neuroepithelial cell proliferation. However, the effect of ethanol on subventricular basal progenitors which generate majority of the cortical layers is not known.
  
  
  METHODS
  We utilized spontaneously immortalized rat brain neuroblasts obtained from cultures of 18-day-old fetal rat cerebral cortices using in vitro ethanol exposures and an in utero binge model. In the in vitro acute model, cells were exposed to 86 mM ethanol for 8, 12 and 24 h. The second in vitro model comprised of chronic intermittent ethanol (CIE) exposure which consisted of 14 h of ethanol treatment followed by 10 h of withdrawal with three repetitions.
  
  
  RESULTS
  E18 neuroblasts expressing Tbr2 representing immature basal progenitors displayed significant reduction of proliferation in response to ethanol in both the models. The decreased proliferation was accompanied by absence of apoptosis or autophagy as illustrated by FACS analysis and expression of apoptotic and autophagic markers. The BrdU incorporation assay indicated that ethanol enhanced the accumulation of cells at G1 with reduced cell number in S phase. In addition, the ethanol-inhibited basal neuroblasts proliferation was connected to decrease in cyclin D1 and Rb phosphorylation indicating cell cycle arrest. Further, in utero ethanol exposure in pregnant rats during E15-E18 significantly decreased Tbr2 and cyclin D1 positive cell number in cerebral cortex of embryos as assessed by cell sorting analysis by flow cytometry.
  
  
  CONCLUSIONS
  Altogether, the current findings demonstrate that ethanol impacts the expansion of basal progenitors by inducing cytostasis that might explain the anomalies of cortico-cerebral development associated with fetal alcohol syndrome.
authors.affiliation: Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, TX, 79430, USA.
authors.forename: Amanjot Kaur
authors.initials: AK
authors.lastname: Riar
authors.affiliation: Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, TX, 79430, USA.|South Plains Alcohol and Addiction Research Center, Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, TX, 79430, USA.
authors.forename: Madhusudhanan
authors.initials: M
authors.lastname: Narasimhan
authors.affiliation: Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, TX, 79430, USA.
authors.forename: Mary Latha
authors.initials: ML
authors.lastname: Rathinam
authors.affiliation: Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, TX, 79430, USA.|South Plains Alcohol and Addiction Research Center, Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, TX, 79430, USA.
authors.forename: George I
authors.initials: GI
authors.lastname: Henderson
authors.affiliation: Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, TX, 79430, USA. lenin.mahimainathan@ttuhsc.edu.|South Plains Alcohol and Addiction Research Center, Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, TX, 79430, USA. lenin.mahimainathan@ttuhsc.edu.
authors.forename: Lenin
authors.initials: L
authors.lastname: Mahimainathan
mesh_terms: D020268:Alcohol-Induced Disorders, Nervous System / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D019938:Cyclin D1 / Q000378:metabolism; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000378:metabolism* / Q000473:pathology; D005625:Frontal Lobe / Q000378:metabolism* / Q000473:pathology; D016193:G1 Phase / Q000187:drug effects*; D058953:Neural Stem Cells / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D051381:Rats; D016196:S Phase / Q000187:drug effects*; D020825:T-Box Domain Proteins / Q000378:metabolism
chemical_list: C530106:Ccnd1 protein, rat; D020825:T-Box Domain Proteins; D019938:Cyclin D1; D000431:Ethanol