ABSTRACT
Smoking by pregnant women poses a potential risk on the unborn child because nicotine can easily be transported from the maternal to the fetal physiological system. Our previous studies have shown that developing brains are sensitive to nicotine-induced cell loss if nicotine was administered during the brain growth spurt (early postnatal) in a rat model system. The purpose of this study was to examine whether nicotine exposure prenatally (first two trimesters equivalent in rats) would lead to Purkinje cell loss in the developing cerebellar vermis. Pregnant female rats were subcutaneously implanted with 0 (placebo), 15 (NIC 15), or 25 (NIC 25) mg nicotine pellets (21-day time released) on gestational day (GD) 0. An additional control group receiving no implantation was also introduced (normal). One pup from each litter was sacrificed on postnatal day (PD) 10 and the cerebellar vermis was processed for stereological cell counting of Purkinje cells. No significant effects of prenatal nicotine treatment were found in the forebrain, cerebellum, and brainstem weights. Similarly, the assessments of volume, Purkinje cell number, and Purkinje cell density found no significant differences among all treatment groups. Taken together, the current and a previous finding, it suggests that there is a temporal window of vulnerability to nicotine-induced Purkinje cell loss in the developing cerebellar vermis.
Subject(s)
Cell Death/drug effects , Cerebellum/drug effects , Nicotine/toxicity , Nicotinic Agonists/toxicity , Prenatal Exposure Delayed Effects , Purkinje Cells/drug effects , Analysis of Variance , Animals , Body Weight , Brain/anatomy & histology , Cell Count , Cerebellum/cytology , Cerebellum/embryology , Dose-Response Relationship, Drug , Drug Implants/administration & dosage , Female , Male , Organ Size , Pregnancy , Random Allocation , Rats , Rats, Sprague-DawleyABSTRACT
Nicotine affects functions of the central nervous system. A previous study showed that developing cerebellar Purkinje cells are targets for early postnatal nicotine exposure. In this study, we assessed the effects of long-term nicotine exposure on mature cerebellar Purkinje cells. This is particularly relevant since the majority of smokers are exposed to nicotine over a long period. Female adult Sprague-Dawley rats received three doses of nicotine (0.01%, 0.03%, or 0.06%) through their sole water source. After 8 weeks of nicotine exposure, the cerebellar vermis was removed and processed for stereological cell counting. The results showed that this long-term nicotine treatment did not change the cerebellum weight or the size (volume) of the cerebellar vermis. The long-term nicotine treatment regimen did result in a significant loss of mature Purkinje cells in the cerebellum, however, such a loss of Purkinje cells was not nicotine dose-related. These findings indicated that the mature adult cerebellum is susceptible to the damaging effects of nicotine in depleting Purkinje cells in the cerebellum.
Subject(s)
Cerebellum/drug effects , Nicotine/toxicity , Purkinje Cells/drug effects , Administration, Oral , Animals , Body Weight/drug effects , Cell Count , Cerebellum/pathology , Dose-Response Relationship, Drug , Female , Organ Size/drug effects , Purkinje Cells/cytology , Rats , Rats, Sprague-Dawley , Time FactorsABSTRACT
BACKGROUND: One popular mechanism proposed to account for alcohol-induced brain damage is the generation of free radicals after alcohol exposure. Therefore, it is reasonable to hypothesize that administration of an antioxidant should reduce the severity of alcohol-induced brain damage. Recently, melatonin has been shown to be an effective free-radical scavenger. In this study, the ability of melatonin to attenuate alcohol-induced cerebellar Purkinje cell loss in the cerebellar vermis and lobule I was assessed. METHODS: Sprague-Dawley rat pups were used in this study. These neonatal pups were exposed to alcohol (4.5 g/kg), melatonin (10 mg/kg), both alcohol and melatonin, or control vehicle via artificial-rearing methods from postnatal day (PD) 4 to PD 9. Alcohol, melatonin, or control vehicle was mixed with milk formula in 2 of the daily 12 feedings. Pups were killed 90 min after the beginning of the second alcohol feeding on PD 9. RESULTS: Alcohol significantly reduced the Purkinje cell numbers in the vermis and lobule I, with a higher percentage of cell loss in lobule I compared with the vermis. However, melatonin, per se, neither affected the Purkinje cell number nor diminished alcohol-induced Purkinje cell loss. CONCLUSIONS: Melatonin was not effective in attenuating alcohol-induced loss of Purkinje cells in our neonatal rat model system, even though such a dosage of melatonin is capable of reversing free radical-induced damage in other tissues.
