Significant modulation of mitochondrial electron transport system by nicotine in various rat brain regions.
The mitochondrion is the organelle responsible for generation of most usable energy in a cell. It also plays an important role in a series of physiological processes such as apoptosis and proliferation. Although previous studies have demonstrated that nicotine modulates the morphology and function of mitochondria, the mechanism(s) underlying these effects is largely unknown. In this study, using a microarray consisting of 4793 clones derived from a mouse dopamine cDNA library, we profiled the gene expression patterns for six brain regions (amygdala, hippocampus, nucleus accumbens, prefrontal cortex, striatum and ventral tegmental area) of female Sprague-Dawley rats subjected to nicotine treatment for 7days through osmotic minipump infusion. We identified a number of genes and pathways, including components of the electron transport system of mitochondria, such as cytochrome c oxidase subunit I (Mt-co1), Mt-co2, Mt-co3, cytochrome b (Mt-cyb), mitochondrial NADH dehydrogenase 4 (Mt-nd4), and Mt-nd6, that were significantly modulated by nicotine in multiple brain regions. Bioinformatics analysis provided evidence that Gene Ontology categories related to the electron transport system were overrepresented in each brain region. Finally, the results from the microarray analysis were verified by quantitative RT-PCR for four representative genes. Together, our findings imply that mitochondria are involved in neuronal adaptation to chronic nicotine exposure.
Wang
Ju
J
Department of Psychiatry and Neurobehavioral Sciences, Section of Neurobiology, University of Virginia, 1670 Discovery Drive, Suite 110, Charlottesville, VA 22911, United States.
Kim
Jong-Man
JM
Donovan
David M
DM
Becker
Kevin G
KG
Li
Ming D
MD
D000818:Animals; D001921:Brain / Q000187:drug effects*; D004579:Electron Transport / Q000187:drug effects*; D005260:Female; D005731:Ganglionic Stimulants / Q000494:pharmacology*; D020869:Gene Expression Profiling; D008928:Mitochondria / Q000187:drug effects*; D009538:Nicotine / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D005731:Ganglionic Stimulants; D009538:Nicotine