Document Detail


The role of cortisol in chronic binge alcohol-induced cerebellar injury: Ovine model.
MedLine Citation:
PMID:  23218665     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Women who drink alcohol during pregnancy are at high risk of giving birth to children with neurodevelopmental disorders. Previous reports from our laboratory have shown that third trimester equivalent binge alcohol exposure at a dose of 1.75 g/kg/day results in significant fetal cerebellar Purkinje cell loss in fetal sheep and that both maternal and fetal adrenocorticotropin (ACTH) and cortisol levels are elevated in response to alcohol treatment. In this study, we hypothesized that repeated elevations in cortisol from chronic binge alcohol are responsible at least in part for fetal neuronal deficits. Animals were divided into four treatment groups: normal control, pair-fed saline control, alcohol and cortisol. The magnitude of elevation in cortisol in response to alcohol was mimicked in the cortisol group by infusing pregnant ewes with hydrocortisone for 6 h on each day of the experiment, and administering saline during the first hour in lieu of alcohol. The experiment was conducted on three consecutive days followed by four days without treatment beginning on gestational day (GD) 109 until GD 132. Peak maternal blood alcohol concentration in the alcohol group was 239 ± 7 mg/dl. The fetal brains were collected and processed for stereological cell counting on GD 133. The estimated total number of fetal cerebellar Purkinje cells, the reference volume and the Purkinje cell density were not altered in response to glucocorticoid infusion in the absence of alcohol. These results suggest that glucocorticoids independently during the third trimester equivalent may not produce fetal cerebellar Purkinje cell loss. However, the elevations in cortisol along with other changes induced by alcohol could together lead to brain injury seen in the fetal alcohol spectrum disorders.
Authors:
Shannon E Washburn; Ursula Tress; Emilie R Lunde; Wei-Jung A Chen; Timothy A Cudd
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-12-05
Journal Detail:
Title:  Alcohol (Fayetteville, N.Y.)     Volume:  47     ISSN:  1873-6823     ISO Abbreviation:  Alcohol     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-14     Completed Date:  2013-06-27     Revised Date:  2014-02-04    
Medline Journal Info:
Nlm Unique ID:  8502311     Medline TA:  Alcohol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  53-61     Citation Subset:  IM    
Copyright Information:
Published by Elsevier Inc.
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MeSH Terms
Descriptor/Qualifier:
Alcoholic Intoxication / complications,  pathology,  physiopathology*
Animals
Cerebellum / drug effects*,  pathology
Disease Models, Animal
Female
Fetal Alcohol Spectrum Disorders / pathology
Hydrocortisone / blood,  pharmacology*
Pregnancy
Purkinje Cells / drug effects
Sheep, Domestic
Grant Support
ID/Acronym/Agency:
AA10940/AA/NIAAA NIH HHS; K08 AA018166/AA/NIAAA NIH HHS; K08AA18166/AA/NIAAA NIH HHS; R01 AA010940/AA/NIAAA NIH HHS
Chemical
Reg. No./Substance:
WI4X0X7BPJ/Hydrocortisone
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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