Maternal smoking during pregnancy is associated with a number of detrimental outcomes including increased rates of behavioral and psychological disorders in children that persist into adolescence and adulthood. Maternal smoking during pregnancy is also significantly associated with an increased propensity for addiction to nicotine and increased difficulty in quitting smoking later in life. Animal studies using prenatal nicotine treatment have found similar results, however the mechanisms by which prenatal nicotine exposure contributes to the development of these disorders and predisposition for addiction are still unclear. I used a chronic prenatal nicotine treatment paradigm and whole genome microarray analysis of the ventral tegmental area to determine the persistent effects of nicotine on gene expression in adolescent male and female Sprague-Dawley rats. After identifying genes significantly regulated by nicotine, pathway analysis was employed to determine over-represented biological functions with relevance to chronic prenatal nicotine treatment in the rats that may contribute to development of behavioral and psychological disorders and addiction. I found that prenatal nicotine exposure regulated gene expression in the VTA that persisted into adolescence, thirty days after nicotine treatment had ended. Additionally, the differences in the gene expression profiles of the male and female adolescent rats prenatally treated with nicotine were striking. Two thousand nine hundred twenty-nine genes in the male adolescent rats and 1,376 genes in the female adolescent rats were found to be significantly regulated by nicotine, with the genders sharing only 115 genes regulated in common. Particular genes of interest were identified in both males and females that contribute to the regulation of neurotransmission and may be involved in the development of behavioral and psychological disorders as well as addiction.
|Advisor:||Perry, David C.|
|School:||The George Washington University|
|Department:||Biochemistry and Molecular Biology|
|School Location:||United States -- District of Columbia|
|Source:||MAI 50/04M, Masters Abstracts International|
|Subjects:||Neurosciences, Biochemistry, Developmental biology|
|Keywords:||ADHD, Behavioral disorders, Genome expression profile, Microarray, Prenatal nicotine exposure, VTA|
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