In utero ethanol exposure increases proenkephalin, a precursor of a neuropeptide that is inhibitory to neuronal growth.
BACKGROUND
One of the effects of fetal alcohol syndrome (FAS) is altered motor function. In an attempt to elucidate a potential cause of this ethanol-associated damage, we investigated the effects of in utero ethanol exposure on the production of proenkephalin (PE).


METHODS
PE is the precursor of met- and leu-enkephalin, two neuropeptides that inhibit the proliferation of neurons and astrocytes. PE mRNA and PE peptide were measured in the striatum and nucleus accumbens because of the importance of these brain regions to motor function, their sensitivity to the effects of in utero ethanol exposure, and their high concentration of PE mRNA and PE peptide.


RESULTS
The present studies demonstrated that in utero ethanol exposure is associated with increased PE mRNA in the striatum and nucleus accumbens. Of specific interest is the elevation in PE mRNA in the nucleus accumbens in 5-, 12-, and 19-day-old ethanol-exposed offspring and the fact that this change persists for at least 19 days after the last exposure to ethanol. Further studies of postnatal day 19 (PN19) offspring localized the abnormality in the nucleus accumbens to the core region, an area that contains enkephalinergic projections to another motor area-the substantia nigra. In the nucleus accumbens, the increased PE mRNA was associated with a greater proportion of PE-expressing neurons that have 41% to 60% of the cell area covered by grains associated with PE mRNA.


CONCLUSIONS
Although we were not able to detect a change in the concentration of the PE peptide in the nucleus accumbens or striatum, we cannot rule out the possibility that the increase in PE mRNA was reflective of a functional abnormality.
Druse
M J
MJ
Department of Molecular & Cellular Biochemistry, Loyola University Chicago, Stritch School of Medicine, Maywood, Illinois 60153, USA. mmanteu@wpo.it.luc.edu
Hao
H L
HL
Eriksen
J L
JL
D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004745:Enkephalins / Q000187:drug effects* / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000378:metabolism; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D011498:Protein Precursors / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D002492:Central Nervous System Depressants; D004745:Enkephalins; D011498:Protein Precursors; D012333:RNA, Messenger; C029992:proenkephalin; D000431:Ethanol