Investigating the Influence of Maternal Nicotine and Alcohol Co-Exposure in Genetic Profiles of Dopamine Neurons in Newborns



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Nicotine and alcohol are two of the most commonly used and abused addictive drugs and their usage has been linked to significant health hazards. People who smoke are much more likely to drink, and vice versa. Emerging studies have shown the effects of these drugs independently on gene expression within many brain regions implicated in the reward pathway. Dopaminergic (DA) neurons originating from the ventral tegmental area (VTA) of the brain are activated by addictive drugs, which is known to contribute to addiction. Using a well-established rat model for both nicotine and alcohol perinatal exposure, we have investigated the mRNA and miRNA gene expression of these DA neurons of the VTA in rat pups exposed to alcohol and joint nicotine-alcohol perinatally. Employing microarray analysis, we found alcohol alone and nicotine-alcohol co-exposure causes differential gene and miRNA expression within the VTA DA neurons. Enriched biological pathways following perinatal alcohol and nicotine-alcohol co-exposure suggested alterations during the neurodevelopmental processes at the cellular level through modulation of genes associated with neural migration, neurodevelopment and apoptosis. We expanded this study to further include non-DA neurons in order to compare their differential expression following perinatal alcohol and nicotine-alcohol co-exposure. We found combined nicotine-alcohol perinatal co-exposure on DA neurons enriched pathways related to neurodegeneration such as Parkinson disease, Huntington disease and Alzheimer disease more significantly than alcohol perinatal exposure alone. We investigated the neuron populations within the sub-regions of the VTA following perinatal nicotine exposure using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) to investigate GABA, DA, and glutamate neurons. We found perinatal nicotine exposure to significantly affect DA neurons within the paranigral nucleus (PN) sub-region of the VTA with the parainterfascicular nucleus (PIF) sub-region containing a more diverse population of neurons.



Nicotine, Alcohol


Portions of this document appear in: Kazemi, T., Avci, N.G., Keller, R.F. et al. Investigating the influence of perinatal nicotine exposure on genetic profiles of neurons in the sub-regions of the VTA. Sci Rep 10, 2419 (2020).; and in: Kazemi, T., Huang, S., Avci, N.G. et al. Investigating the influence of perinatal nicotine and alcohol exposure on the genetic profiles of dopaminergic neurons in the VTA using miRNA–mRNA analysis. Sci Rep 10, 15016 (2020).; and in: Kazemi, T., Huang, S., Avci, N.G. et al. Investigating the effects of chronic perinatal alcohol and combined nicotine and alcohol exposure on dopaminergic and non-dopaminergic neurons in the VTA. Sci Rep 11, 8706 (2021).