Gene expression profiling of midbrain dopamine neurons upon gestational nicotine exposure

Med Biol Eng Comput. 2017 Mar;55(3):467-482. doi: 10.1007/s11517-016-1531-8. Epub 2016 Jun 2.

Abstract

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.

Keywords: Dopamine; Gestational nicotine; Microarray; Neurological diseases; VTA.

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Cluster Analysis
  • Dopaminergic Neurons / drug effects
  • Dopaminergic Neurons / metabolism*
  • Down-Regulation / drug effects
  • Female
  • Gene Expression Profiling*
  • Gene Ontology
  • Mesencephalon / cytology*
  • Molecular Sequence Annotation
  • Nicotine / pharmacology*
  • Oligonucleotide Array Sequence Analysis
  • Pregnancy
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction
  • Reproducibility of Results
  • Software
  • Up-Regulation / drug effects

Substances

  • RNA, Messenger
  • Nicotine