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PUBLICATIONS: 2004
Fetal alcohol exposure alters neurosteroid levels in the developing rat brain.
Caldeira JC, Wu Y, Mameli M, Purdy RH, Li PK, Akwa Y, Savage DD, Engen JR, Valenzuela CF.
J Neurochem. 2004 Sep;90(6):1530-9.
ABSTRACT Neurosteroids
are modulators of neuronal function that may play important roles in
brain maturation. We determined whether chronic prenatal ethanol
exposure altered neurosteroid levels in the developing brain. Rat dams
were exposed to: (i) a 5% ethanol-containing liquid diet that produces
peak maternal blood alcohol levels near the legal intoxication limit
(approximately 0.08 g/dL); (ii) an isocaloric liquid diet containing
maltose-dextrin instead of ethanol with pair-feeding; (iii) rat chow ad
libitum. Neurosteroid levels were assessed in offspring brains using
radioimmunoassay or gas chromatography-mass spectrometry techniques. A
prenatal ethanol exposure-induced increase in pregnenolone sulfate
levels, but not dehydroepiandrosterone sulfate levels, was evident at
the earliest time point studied (embryonic day 14). This effect lasted
until post-natal day 5. Levels of other neurosteroids were assessed at
embryonic day 20; pregnenolone levels, but not allopregnanolone levels,
were elevated. Pregnenolone sulfate levels were not altered in the
maternal brain. Neither pregnenolone nor pregnenolone sulfate levels
were significantly altered in the fetal liver, placenta and maternal
blood, indicating that the effect of ethanol is not secondary to
accumulation of peripherally-produced steroids. Fetal ethanol exposure
has been shown to decrease both cellular and behavioral responsiveness
to neurosteroids, and our findings provide a plausible explanation for
this effect.
Pubmed:
15341536
What mass spectrometry can reveal about protein function.
Pubmed:
15042158
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