Gene expression profiling of midbrain dopamine neurons upon gestational nicotine exposure

Pınar Kanlikilicer, Die Zhang, Andrei Dragomir, Yasemin M. Akay, Metin Akay

Maternal smoking during pregnancy is associated with low birth weight, increased risk of stillbirth, conduct disorder, attention-deficit/hyperactivity disorder and neurocognitive deficits. Ventral tegmental area dopamine (DA) neurons in the mesocorticolimbic pathway were suggested to play a critical role in these pathological mechanisms induced by nicotine. Nicotine-mediated changes in genetic expression during pregnancy are of great interest for current researchers. We used patch clamp methods to identify and harvest DA and non-DA neurons separately and assayed them using oligonucleotide arrays to elucidate the alterations in gene expressions in these cells upon gestational nicotine exposure. Microarray analysis identified a set of 135 genes as significantly differentially expressed between DA and non-DA neurons. Some of the genes were found to be related to neurological disease pathways, such as Alzheimer's disease, Parkinson's disease and Huntington's disease. Significantly up-/down-regulated genes found in DA neurons were mostly related to G-protein-coupled protein receptor signaling and developmental processes. These alterations in gene expressions may explain, partially at least, the possible pathological mechanisms for the diseases induced by maternal smoking.