PRENATAL NICOTINE EXPOSURE ALTERS GENE EXPRESSION IN A SEXUALLY DIMORPHIC MANNER
Open Access
- Author:
- Foreman, Jennifer E
- Graduate Program:
- Genetics
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- February 26, 2007
- Committee Members:
- Guy F Barbato, Committee Chair/Co-Chair
Gerald Eugene Mc Clearn, Committee Member
Laura Klein, Committee Member
John Patrick Vanden Heuvel, Committee Member
David John Vandenbergh, Committee Member - Keywords:
- prenatal nicotine
microarray
Pou3f1
Kif1a
gene networks
sex differences - Abstract:
- Nicotine has been demonstrated to regulate gene expression in brain reward pathways. In human adults these changes in expression are hypothesized to play a role in the maintenance of drug taking; however, how these changes affect the developing nervous system through second hand exposure from the mother during fetal development is just beginning to be understood. Previous research in prenatally exposed mouse pups, sacrificed on day of birth (PN0), demonstrated sexually dimorphic patterns of gene expression in response to nicotine. This dissertation work extends these findings by investigating how prenatal nicotine affects gene expression patterns in adolescents. The persistence of sexually dimorphic gene response to nicotine is of particular interest due to previously reported sex differences in the results of a behavior experiment conducted on the adolescent animals used in this study. Early nicotine exposure could permanently change the organization of the brain in a sexually dimorphic manner by altering gene expression. The use of Bioinformatic resources allows the interrogation of the genes exhibiting sexually dimorphic response to identify potential gene networks that nicotine may be acting upon. The use of these resources allows the merger of publicly available data with the microarray studies that gives a greater understanding of the biology underlying observed patterns. In this manner I have identified genes that are sexually differentially regulated by nicotine and suggest potential modes of action for the large number of sexually dimorphic responses seen after nicotine exposure.