Impact of low dose nicotine on brain-derived neurotrophic factor after global hypoxia in newborn piglets.

Objectives: The aim of this study was to assess the effect of low-dose nicotine on the expression of brain-derived neurotrophic factor (BDNF) mRNA, its antisense alternative splice form brain-derived neurotrophic factor antisense (BDNF-AS), and its protein levels after global hypoxia in newborn piglets. This study also sought to explore the regulatory role of BDNF-AS on BDNF mRNA.

Methods: 41 newborn piglets were randomised after hypoxia to one of two different infusions of nicotine (18 or 46 μg/kg/h, respectively) or to a control group receiving saline. After 4 h of infusion, the piglets were euthanized and brain samples from the hippocampus and temporal cortex were collected for quantification of BDNF mRNA, BDNF-AS and BDNF protein.

Results: In the hippocampus, significant lower expression of BDNF mRNA was observed in the animals treated with 46 μg/kg/h of nicotine compared to the group receiving 18 μg/kg/h (p=0.047) and the control group (p=0.017). The BDNF mRNA and BDNF-AS showed a strong correlation (r=0.63, p<0.001) in the hippocampus samples and moderate, but significant, correlation (r=0.36, p=0.021) in the samples from the cortex. We found no differences in BDNF mRNA between the groups in the cortex samples. Protein levels of BDNF were similar in all three groups in both the hippocampus and cortex samples.

Conclusions: Our results suggest that low concentrations of nicotine might have a short-term effect on the expression of BDNF mRNA. However, the BDNF protein levels remained unchanged at the same time point and the long-term impact on the nervous system remains unclear.