Gene expression profiling of midbrain dopamine neurons upon gestational nicotine exposure

• DOI: 10.1007/s11517-016-1531-8
• Publication Date: 2016-06-02T14:28:29Z
• Authors: Pınar Kanlikilicer; Die Zhang; Andrei Dragomir; Yasemin M. Akay; Metin Akay
• Keywords: 0301 basic medicine; Nicotine; Dopaminergic Neurons; Gene Expression Profiling; Action Potentials; Down-Regulation; Reproducibility of Results; Molecular Sequence Annotation; Real-Time Polymerase Chain Reaction; Up-Regulation; 3. Good health; Rats, Sprague-Dawley; 03 medical and health sciences; Gene Ontology; Mesencephalon; Pregnancy; Animals; Cluster Analysis; Female; RNA, Messenger; Software; Oligonucleotide Array Sequence Analysis

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.