Nicotine administration differentially affects gene expression in the maternal and fetal circadian clock.
Exposure to nicotine by active and passive cigarette smoke is a common public health problem. Recent studies have demonstrated that human fetuses are also exposed to significant levels of nicotine and that there is a five-fold increase in the incidence of Sudden Infant Death Syndrome among infants born to smoking mothers. We examined the effect of nicotine administration and expression of the immediate early gene c-fos in the maternal and fetal rat brain by in situ hybridization. Nicotine injection (1 mg/kg s.c.) on embryonic day 20 (E20) induced detectable c-fos mRNA in the maternal habenula and hypothalamic paraventricular nucleus whereas, in the fetal brain, c-fos was induced in both these structures and also in the suprachiasmatic nucleus (SCN). Nicotine-induced c-fos expression in the fetal SCN was confirmed by Northern analysis and found to return to near basal levels by 3 h post-injection. These responses were blocked by pre-administration of mecamylamine, indicating that the effect of nicotine is mediated through the cholinergic system. Investigation of the development of this response revealed that nicotine failed to induce c-fos expression in the SCN on E16, caused minimal expression on E18, robust expression on E20 and postnatal day 0 (P0), and no expression on P2 or thereafter. These observations suggest that an alteration in the composition of the nicotinic receptors (nAChR), or the subsequent intracellular responses leading to c-fos expression, occurs in the SCN during the perinatal period. Induction of c-fos mRNA in the SCN by light has been associated with phase-shifts of the circadian system, however, the behavioral consequences of the transient sensitivity of the fetal and neonatal SCN to nicotine administration and the consequences for maternal-fetal entrainment remain to be directly determined.
Clegg
D A
DA
Department of Biological Sciences, Stanford University School of Medicine, CA 94305, USA.
O'Hara
B F
BF
Heller
H C
HC
Kilduff
T S
TS
D000818:Animals; D001345:Autoradiography; D001683:Biological Clocks; D015152:Blotting, Northern; D001921:Brain / Q000000981:diagnostic imaging*; D002940:Circadian Rhythm; D005260:Female; D015870:Gene Expression; D017403:In Situ Hybridization; D009538:Nicotine / Q000494:pharmacology*; D011247:Pregnancy; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D011859:Radiography; D051381:Rats; D017207:Rats, Sprague-Dawley
D016760:Proto-Oncogene Proteins c-fos; D009538:Nicotine