Ta. Trauth et al., Persistent c-fos induction by nicotine in developing rat brain regions: Interaction with hypoxia, PEDIAT RES, 45(1), 1999, pp. 38-45
Prenatal nicotine exposure evokes postnatal CNS cell loss. We administered
nicotine to pregnant rats throughout gestation and neonatal brains were exa
mined for expression of c-fos, a nuclear transcription factor involved in d
ifferentiation and cell death. The nicotine group showed persistent c-fos o
verexpression in the forebrain long after termination of exposure; in the b
rainstem, overexpression was apparent both after birth and at the end of th
e second postnatal week. In contrast to these effects, postnatal administra
tion on d 1-4 caused persistent c-fos only at systemically toxic doses and
treatment at subsequent ages did not cause induction at ail. We also determ
ined whether prenatal nicotine exposure would sensitize the brain to a subs
equent postnatal episode of hypoxia comparable to that experienced during p
arturition. Hypoxia evoked acute stimulation of c-fos with a regional selec
tivity and ontogenetic profile differing from those of prenatal nicotine an
d this acute response was reduced by prenatal nicotine treatment. Persisten
t c-fos elevation is a harbinger of cell death, a relationship that provide
s an underlying mechanism for eventual cell deficits that appear after feta
l nicotine exposure. Nicotine's interference with the acute c-fos stimulati
on caused by a subsequent episode of hypoxia may indicate a further comprom
ise of cellular repair mechanisms.