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</o:shapelayout></xml><![endif]--></head><body lang=EN-US link=blue vlink=purple><div class=WordSection1><p class=MsoNormal><span style='font-size:9.0pt'><o:p> </o:p></span></p><p class=MsoNormal align=center style='text-align:center;page-break-after:avoid'><b><span style='font-size:16.0pt;font-family:"Tahoma","sans-serif"'>PhD Dissertation Defense<o:p></o:p></span></b></p><p class=MsoNormal align=center style='text-align:center;page-break-after:avoid'><b><span style='font-size:16.0pt;font-family:"Tahoma","sans-serif"'><o:p> </o:p></span></b></p><p class=MsoNormal align=center style='text-align:center'><b><span style='font-size:14.0pt;font-family:"Tahoma","sans-serif"'>m<span style='text-transform:uppercase'>RNA EXPRESSION ANALYSIS OF MIDBRAIN DOPAMINE NEURONS <o:p></o:p></span></span></b></p><p class=MsoNormal align=center style='text-align:center'><b><span style='font-size:14.0pt;font-family:"Tahoma","sans-serif";text-transform:uppercase'>IN RESPONSE TO NICOTINE INTAKE DURING MATURATION<o:p></o:p></span></b></p><p class=MsoNormal align=center style='text-align:center'><b><o:p> </o:p></b></p><p class=MsoNormal align=center style='text-align:center'><b><span style='font-size:14.0pt;font-family:"Tahoma","sans-serif"'>Pinar Kanlikilicer <o:p></o:p></span></b></p><p class=MsoNormal align=center style='text-align:center'><b><span style='font-size:12.0pt'><o:p> </o:p></span></b></p><p class=MsoNormal align=center style='text-align:center'><b><span style='font-size:12.0pt'>Date: Tuesday, Aug. 13<sup>th</sup>, <sup> </sup>2013<o:p></o:p></span></b></p><p class=MsoNormal align=center style='text-align:center'><b><span style='font-size:12.0pt'><o:p> </o:p></span></b></p><p class=MsoNormal align=center style='text-align:center'><b><span style='font-size:12.0pt'>Location:</span></b> <span style='font-size:12.0pt'>Science & Engineering Research Center (SERC) – Rm 2018<o:p></o:p></span></p><p class=MsoNormal align=center style='text-align:center'><b><span style='font-size:12.0pt'>Time: 11:00 AM<o:p></o:p></span></b></p><p class=MsoNormal align=center style='text-align:center'><b><span style='font-size:12.0pt'><o:p> </o:p></span></b></p><p class=MsoNormal align=center style='text-align:center'><b><span style='font-size:12.0pt'>Committee Co-Chairs: <o:p></o:p></span></b></p><p class=MsoNormal align=center style='text-align:center'><span style='font-size:12.0pt'>Dr. Metin Akay<o:p></o:p></span></p><p class=MsoNormal align=center style='text-align:center'>Dr. Yasemin Akay<o:p></o:p></p><p class=MsoNormal align=center style='text-align:center'><b><o:p> </o:p></b></p><p class=MsoNormal><span style='font-size:12.0pt'><o:p> </o:p></span></p><p class=MsoNormal><span style='font-size:12.0pt'>Addictive substances including cocaine, nicotine and amphetamine exert their reinforcing properties through the dopamine system. The majority of dopamine (DA) neurons are located in the ventral midbrain comprising of the substantia nigra (SN) and the ventral tegmental area (VTA). Nicotine has been suggested as both neuroprotective and neurotoxic on the central nervous system (CNS). For many neurological disorders, nicotine has been found to be protective against neurodegeneration in Alzheimer’s disease, dopaminergic cell death in SN of patients with Parkinson’s disease (PD) and neurodegeneration in Huntington’s disease. On the other hand, nicotine was shown to be neurotoxic on the developing brain by leading to structural alterations in the brain regions involved in cognition, learning, and memory.<o:p></o:p></span></p><p class=MsoNormal><span style='font-size:12.0pt'><o:p> </o:p></span></p><p class=MsoNormal><span style='font-size:12.0pt'>Previous studies suggested that the expression of neuroprotective genes was significantly different in the VTA and SN dopamine neurons and nicotine mediated neuroprotection in PD. These studies encouraged us to investigate how nicotine changes the expression of these differentially expressed neuroprotective genes (PACAP, LPL and GRP) in the VTA and the SN at different age stages. Our results suggested that only the LPL gene significantly differentially expressed between the VTA and the SN in 24-months old rats. In addition, nicotine treatment did not show any up-regulatory effects on the expression of neuroprotective genes in rats after 12-months maturation.<o:p></o:p></span></p><p class=MsoNormal><span style='font-size:12.0pt'><o:p> </o:p></span></p><p class=MsoNormal><span style='font-size:12.0pt'>We also investigated the whole-genome expression of midbrain dopaminergic and non-dopaminergic neurons in response to gestational nicotine in newborn rats (PN 7-14). Patch-clamp electrophysiology was used to select and collect DA and non-DA neuron in newborn rats during the first week of maturation. Then, we use the microarray technique to analyze the gene expression of these neurons in response to gestational nicotine. <o:p></o:p></span></p><p class=MsoNormal><span style='font-size:12.0pt'><o:p> </o:p></span></p><p class=MsoNormal><span style='font-size:12.0pt'>We identified a set of 135 genes as significantly differentially expressed between dopaminergic and non-dopaminergic neurons upon exposure to gestational nicotine. The roles of the genes previously implicated in Alzheimer’s Disease, Parkinson’s Disease, Huntington’s Disease, arachidonic acid and linoleic acid metabolism were identified. We also identified significantly regulated genes by gestational nicotine in DA and non-DA neurons. These specific genes in DA neurons could be paramount in developmental processes.<o:p></o:p></span></p><p class=MsoNormal><o:p> </o:p></p><p class=MsoNormal><o:p> </o:p></p></div></body></html>