Persistent c-fos induction by nicotine in developing rat brain regions: interaction with hypoxia.
Prenatal nicotine exposure evokes postnatal CNS cell loss. We administered nicotine to pregnant rats throughout gestation and neonatal brains were examined for expression of c-fos, a nuclear transcription factor involved in differentiation and cell death. The nicotine group showed persistent c-fos overexpression in the forebrain long after termination of exposure; in the brainstem, overexpression was apparent both after birth and at the end of the second postnatal week. In contrast to these effects, postnatal administration on d 1-4 caused persistent c-fos only at systemically toxic doses and treatment at subsequent ages did not cause induction at all. We also determined whether prenatal nicotine exposure would sensitize the brain to a subsequent postnatal episode of hypoxia comparable to that experienced during parturition. Hypoxia evoked acute stimulation of c-fos with a regional selectivity and ontogenetic profile differing from those of prenatal nicotine and this acute response was reduced by prenatal nicotine treatment. Persistent c-fos elevation is a harbinger of cell death, a relationship that provides an underlying mechanism for eventual cell deficits that appear after fetal nicotine exposure. Nicotine's interference with the acute c-fos stimulation caused by a subsequent episode of hypoxia may indicate a further compromise of cellular repair mechanisms.
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Related Subject Headings
- Time Factors
- Smoking
- Recurrence
- Rats, Sprague-Dawley
- Rats
- Proto-Oncogene Proteins c-fos
- Prenatal Exposure Delayed Effects
- Pregnancy
- Pediatrics
- Nicotine
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Time Factors
- Smoking
- Recurrence
- Rats, Sprague-Dawley
- Rats
- Proto-Oncogene Proteins c-fos
- Prenatal Exposure Delayed Effects
- Pregnancy
- Pediatrics
- Nicotine