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ARS Home » Northeast Area » Beltsville, Maryland (BARC) » Beltsville Agricultural Research Center » Animal Biosciences & Biotechnology Laboratory » Research » Publications at this Location » Publication #230045
Title: Significant modulation of mitochondrial electron transport system by nicotine in various rat brain regions

Author
item WANG, JU - UNIVERSITY OF VIRGINIA
item KIM, JONG-MAN - UNIVERSITY OF VIRGINIA
item Donovan, David
item BECKER, KEVIN - NIH
item LI, MING - UNIVERSITY OF VIRGINIA

Submitted to: Mitochondrion
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/21/2009
Publication Date: 1/29/2009
Citation: Wang, J., Kim, J., Donovan, D.M., Becker, K.G., Li, M.D. 2009. Significant modulation of mitochondrial electron transport system by nicotine in various rat brain regions. Mitochondrion. 9:186-195.

Interpretive Summary: Although previous studies have demonstrated that nicotine modulates the morphology and function of mitochondria, the mechanism(s) underlying these effects is largely unknown. As a first step toward understanding nicotine regulation of mitochondrion, mitochondrial gene expression was examined following nicotine exposure. C. Accomplishment-- This work utilized a Dopamine cell-specific cDNA microarray to identify a number of genes and pathways, especially those related to the electron transport system, such as cytochrome c oxidase subunit I (Mtco1), Mtco2, Mtco3, cytochrome b (Mtcyb), mitochondrial NADH dehydrogenase 4, Mtnd4, and Mtnd6, that were significantly modulated by nicotine in multiple brain regions. C. Contribution of Accomplishment to Solving the Problem-- These findings provide new evidence that mitochondria play an important role in nicotine dependence. Studies of this nature build a broad understanding of the effects of nicotine on gene expression. These studies are necessary for the eventual establishment of genes and gene products to be targeted by treatments for such diseases as addiction. These studies help to strengthen an area that is virtually a black box, namely, mitochondrial involvement in behavior and behavior modification.

Technical Abstract: 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, we used a cDNA microarray consisting of 4,793 clones derived from a mouse dopamine cDNA library to characterize genes and biochemical pathways involved in the adaptation of neuron mitochondria to chronic nicotine exposure. Gene expression patterns were profiled for six brain regions (amygdala, hippocampus, nucleus accumbens [NA], prefrontal cortex [PFC], striatum, and ventral tegmental area [VTA)] of female Sprague-Dawley rats subjected to nicotine treatment for 7 days through osmotic minipump infusion. We identified a number of genes and pathways, especially those related to the electron transport system, such as cytochrome c oxidase subunit I (Mtco1), Mtco2, Mtco3, cytochrome b (Mtcyb), mitochondrial NADH dehydrogenase 4, Mtnd4, and Mtnd6, that were significantly modulated by nicotine in multiple brain regions. The results from the microarray analysis were verified by quantitative RT-PCR for four representative genes. Our findings provide new evidence that mitochondria play an important role in nicotine dependence.