Effects of prenatal cocaine exposure on embryonic expression of sonic hedgehog.
Cocaine use by pregnant women may adversely affect development and behavior in the exposed infants. Sonic hedgehog (shh) is a secreted protein that induces development of many structures in the embryo, including dopaminergic cells in the ventral midbrain, the limb buds, and eyes. Because prenatal cocaine exposure has been shown to adversely affect the morphogenesis of these and other systems, the present study was undertaken to test the hypothesis that maternal cocaine treatment would alter shh mRNA expression. Cocaine HCl (60 mg/kg i.p.) was administered to pregnant mice on gestational days 6-8, the time that immediately precedes the appearance of shh. Control dams received i.p. saline. Embryos from gestational days 9-11 were examined by in situ hybridization. The temporal and spatial patterns of shh expression were indistinguishable between embryos from cocaine- and saline-treated dams. Examination of forebrain, midbrain, and midbody spinal cord coronal sections failed to reveal any differences in the dorsoventral and mediolateral localization of shh. The distribution of mRNA for patched (ptc), the membrane receptor for shh, was also indistinguishable between both groups. Chick embryos were next used to examine the direct application of cocaine into the developing brain. Shh distribution was similarly unaffected in these chick embryos. These data show that maternal cocaine treatment during early neural tube development does not significantly alter the expression patterns of shh or ptc mRNA. Thus, congenital defects and behavioral abnormalities associated with maternal cocaine use do not appear to result from altered expression of the shh-ptc pathway.
Koebbe
M J
MJ
Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Golden
J A
JA
Bennett
G
G
Finnell
R H
RH
Mackler
S A
SA
D000014:Abnormalities, Drug-Induced; D000818:Animals; D002642:Chick Embryo; D003042:Cocaine / Q000494:pharmacology*; D004622:Embryo, Mammalian / Q000378:metabolism*; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D053823:Hedgehog Proteins; D051379:Mice; D011247:Pregnancy; D011506:Proteins / Q000235:genetics*; D015534:Trans-Activators