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.

The effect of large unilateral cortical lesions on rubrospinal tract sprouting in newborn rats.

Many previous reports have demonstrated the development of aberrant neural connections in response to neonatal brain lesions. This investigation was undertaken to study possible alterations, particularly axonal sprouting, in rodent rubrospinal projections after neonatal destruction of the corticospinal tract through frontal cortical ablation. The neonatal ablations were made by aspiration in 1 to 2-day-old rats under hypothermic anesthesia. At three to six months after neonatal surgery, the rubrospinal tracts were ablated bilaterally in these small animals as well as in controls, by stereotaxically transecting the ventral tegmental decussation. Animals were killed two to six days after adult surgery, and rubrospinal projections were demonstrated using the Fink-Heimer degeneration stain. No differences in the pattern of rubrospinal projections were observed between animals with neonatal cortical lesions and controls. In all animals rubrospinal projections were located primarily in Rexed's lamina VI with a slight distribution into lamina V and the dorsal portion of lamina VII. Various hypotheses explaining the lack of rubrospinal sprouting after neonatal cortical lesions are presented, along with possible experiments to test these hypotheses.