mRNA EXPRESSION ANALYSIS OF MIDBRAIN DOPAMINE NEURONS IN RESPONSE TO NICOTINE INTAKE DURING MATURATION

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. 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 the 24-month 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. 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 microarray technique to analyze the gene expression of these neurons in response to gestational nicotine. We identified a set of 135 genes identified 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.