Cellular neurosciencePostnatal nicotine and/or intermittent hypercapnic hypoxia effects on apoptotic markers in the developing piglet brainstem medulla
Section snippets
Animal exposures and surgery
Mixed-breed miniature piglets were used in this study. All piglets were received from a commercial piggery within 2 days of birth. Piglets were then randomly assigned to one of the following exposure groups: 1) saline control, 2) nicotine, 3) nicotine and IHH (nic+IHH), or 4) IHH. Piglets in groups 1–3 underwent surgery for implantation of minipumps. Piglets in group 4 had no surgery at all but were exposed to 1 day’s worth of IHH, which was similarly given to piglets in group 3.
Implant of minipumps for nicotine exposure
Osmotic
Piglet characteristics and cotinine concentrations (Table 1)
A total of 52 piglets were studied. Each group had equal numbers of males and females. Across groups and between genders there was no statistically significant difference for any physical parameters including age, body weight at surgery and at death, average daily weight gain, or brain weight (Table 1).
In the group exposed to nicotine only, mean concentrations of cotinine measured at the time of death were 20.3±2.5 ng/ml in serum (males: 19.8±5.0, females: 20.8±1.1), and 92.7±21.8 ng/ml in
Discussion
In this study we found that during early postnatal development: 1. IHH exposure is a greater neurological insult than nicotine alone, 2. when the insults of IHH and nicotine were combined, TUNEL staining increased but to levels that were less than occurred with IHH alone, suggesting that nicotine may be neuroprotective against IHH, and 3. the most striking gender differences were evident for caspase-3 activation after IHH exposure where females were more affected than males, but the apparently
Conclusion
We have shown for the first time that an acute 1 day IHH exposure is more neurotoxic than continuous nicotine infusion over 2 weeks. Compared with our previous data, the peak of apoptotic expression after 1 day of IHH is greater than that seen after 2 or 4 days. Moreover, IHH-induced cell death seems to follow different paths depending on gender, with caspase-3 activation being more prominent in females and apparently activated earlier than in males. Nicotine in the presence of IHH either
Acknowledgments
Research was funded by: NH&MRC #302006. Prof. Waters is supported by an NH&MRC Practitioner Fellowship (#206507). We thank Kellie Tinworth for the care and handling of the piglets during the study period. We also acknowledge the facilities as well as scientific and technical assistance from staff in the NANO Major National Research Facility at the Electron Microscope Unit, the University of Sydney.
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