Alterations in phosphorylated cyclic adenosine monophosphate response element of binding protein activity: a pathway for fetal alcohol syndrome-related neurotoxicity.
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.


METHODS
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).


CONCLUSIONS
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.
Roberson
Robin
R
Unit 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
Cameroni
Irene
I
Toso
Laura
L
Abebe
Daniel
D
Bissel
Stephanie
S
Spong
Catherine Y
CY
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D018891:Dentate Gyrus / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D020258:Neurotoxicity Syndromes / Q000378:metabolism; D011247:Pregnancy
D002352:Carrier Proteins; D000242:Cyclic AMP