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Updated: Jun 26, 2026

Moderate Prenatal Alcohol Exposure and Quantification of Social Behavior in Adult Rats
Published on: December 14, 2014
Alterations in phosphorylated cyclic adenosine monophosphate response element of binding protein activity: a pathway
Robin Roberson1, Irene Cameroni, Laura Toso
1Unit on Perinatal and Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20895, USA. robersor@mail.nih.gov
Objective:
Fetal alcohol syndrome (FAS) is the leading cause of a spectrum of preventable nongenetic learning and behavioral disorders. In adult (FAS) mice, we measured phosphorylated cyclic adenosine monophosphate response element of binding protein (pCREB) staining in hippocampal subregions to evaluate a possible mechanism underlying FAS learning deficits.
Study Design:
Pregnant C57BL6/J mice were treated on gestational day 8 with alcohol or control (saline). After learning assessment, the offspring were perfused for immunohistochemistry and brain sections probed using SER 133 pCREB antibody. Relative staining density was assessed using National Institutes of Health Image software. Statistical analysis included analysis of variance with P < .05 considered significant.
Results:
In all hippocampal subregions, pCREB staining was greater in the control animals than in the alcohol-treated group (P < or = .0001).
Conclusion:
In utero alcohol exposure decreased pCREB activity in hippocampal subregions of adult mice. The dentate gyrus had the most robust cumulative decrease in pCREB staining, suggesting FAS adult learning deficits may correlate to enhanced dentate gyrus neurodegeneration.
Insights
In utero alcohol exposure significantly reduced phosphorylated CREB (pCREB) levels in adult mice brains. This decrease, particularly in the dentate gyrus, may explain learning deficits associated with Fetal Alcohol Syndrome (FAS).
Area of Science:
- Neuroscience
- Developmental Biology
- Toxicology
Background:
- Fetal Alcohol Syndrome (FAS) is a leading cause of preventable learning and behavioral disorders.
- Understanding the molecular mechanisms underlying FAS is crucial for developing interventions.
Purpose of the Study:
- To investigate the role of phosphorylated cyclic adenosine monophosphate response element of binding protein (pCREB) in the hippocampus of adult mice exposed to alcohol in utero.
- To evaluate pCREB levels as a potential mechanism for FAS-related learning deficits.
Main Methods:
- Pregnant mice received alcohol or saline treatment on gestational day 8.
- Offspring underwent learning assessments and subsequent immunohistochemistry for pCREB in hippocampal subregions.
- Staining density was quantified using NIH Image software and analyzed with ANOVA.
Main Results:
- pCREB staining was significantly lower in all hippocampal subregions of alcohol-exposed mice compared to controls (P < .0001).
- The dentate gyrus exhibited the most substantial reduction in pCREB staining.
Conclusions:
- In utero alcohol exposure leads to decreased pCREB activity in adult mouse hippocampus.
- Reduced pCREB in the dentate gyrus suggests a correlation between neurodegeneration and learning deficits in Fetal Alcohol Syndrome.
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