Document Detail


Prevention of alcohol-induced developmental delays and learning abnormalities in a model of fetal alcohol syndrome.
MedLine Citation:
PMID:  16157106     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Prenatal alcohol exposure results in fetal death and neurobehavioral complications including learning impairment. Previously synthetic peptides derived from activity-dependent neurotrophic factor have been shown to prevent aspects of alcohol-induced damage in pregnancy. The objective of this work was to evaluate whether activity-dependent neurotrophic factor-12 could prevent alcohol-induced damage in a model of fetal alcohol syndrome.
STUDY DESIGN: Using a well-characterized model, C57Bl6/J mice on gestational day 8 were treated with placebo, alcohol (30% volume/volume alcohol 0.03 mL/kg), alcohol plus activity-dependent neurotrophic factor-12 30 minutes prior to alcohol, or activity-dependent neurotrophic factor-12 alone. Fetal death was assessed on gestational day 18 (25 litters were evaluated: alcohol, n = 5; placebo, n = 9; alcohol plus activity-dependent neurotrophic factor-12, n = 11). Neonatal behavior tests were performed on postnatal days 1 through 21 with the offspring of 12 dams (alcohol, n = 16; placebo, n = 46; alcohol plus activity-dependent neurotrophic factor-12, n = 23; and activity-dependent neurotrophic factor-12, n = 35). Adult males were tested in the Morris water maze for learning assessment and with the hole punch activity test for exploratory activity. Statistical analysis included Kruskal-Wallis and analysis of variance.
RESULTS: Fetal death was greater in alcohol (67% +/- 13%) vs placebo (8.4% +/- 3%, P < .001). Pretreatment with activity-dependent neurotrophic factor-12 prevented the alcohol-induced fetal death (2.2% +/- 8.1%) with levels similar to control (P = .12). Alcohol exposure caused a delay in achieving developmental milestones, with alcohol achieving milestones later than all other groups (all P < .001). Pretreatment with activity-dependent neurotrophic factor-12 prevented the alcohol-induced milestone delays. In the Morris water maze, the placebo learned, decreasing their latency to find the hidden platform over 70% (P < .01). Alcohol plus activity-dependent neurotrophic factor-12 also significantly learned, with a learning curve not different from placebo (all P > .5) and significantly better than alcohol on days 4, 6, and 7 (all P < .05). Alcohol exposure resulted in significantly less time in hole punch activity (P < .02) than control. Activity-dependent neurotrophic factor-12 pretreatment prevented the alcohol-induced decline, with levels the same as control (P = .1).
CONCLUSION: The novel peptide activity-dependent neurotrophic factor-12 prevents alcohol-induced fetal death and developmental and learning abnormalities in a model of fetal alcohol syndrome. This demonstrates that a single treatment with a peptide is efficacious and may be of value in the prevention of alcohol-induced damage.
Authors:
M Endres; L Toso; R Roberson; J Park; D Abebe; S Poggi; C Y Spong
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  American journal of obstetrics and gynecology     Volume:  193     ISSN:  0002-9378     ISO Abbreviation:  Am. J. Obstet. Gynecol.     Publication Date:  2005 Sep 
Date Detail:
Created Date:  2005-09-13     Completed Date:  2005-10-26     Revised Date:  2011-07-13    
Medline Journal Info:
Nlm Unique ID:  0370476     Medline TA:  Am J Obstet Gynecol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1028-34     Citation Subset:  AIM; IM    
Affiliation:
Unit on Perinatal and Developmental Neurobiology, National Insitute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-0925, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cognition / drug effects
Disease Models, Animal
Ethanol / administration & dosage*
Female
Fetal Alcohol Syndrome / physiopathology*
Fetal Death / prevention & control
Fetal Growth Retardation / prevention & control
Learning / drug effects
Learning Disorders / chemically induced,  prevention & control*
Maze Learning*
Mice
Mice, Inbred Strains
Motor Activity
Nerve Tissue Proteins / therapeutic use*
Pregnancy
Chemical
Reg. No./Substance:
0/Nerve Tissue Proteins; 64-17-5/Ethanol

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


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