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Title: Chronic nicotine exposure regulates the mitochondrial electron transport system in multiple brain regions of rat

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

Submitted to: Society for Neuroscience Abstracts and Proceedings
Publication Type: Abstract Only
Publication Acceptance Date: 8/5/2007
Publication Date: 11/4/2007
Citation: Wang, J., Kim, J., Donovan, D.M., Becker, K.G., Li, M. 2007. Chronic nicotine exposure regulates the mitochondrial electron transport system in multiple brain regions of rat. Society for Neuroscience Abstracts and Proceedings.

Interpretive Summary:

Technical Abstract: Mitochondrion is the organelle responsible for the generation of most of the cellular usable energy ATP and the major source of reactive oxygen species (ROS) in a cell. It also plays important role in a series of physiological processes such as cellular apoptosis and proliferation. Previous studies have demonstrated that nicotine exposure modulates the morphological features and functions of mitochondrion, implicating the involvement of this organelle in the development of nicotine dependence (ND). However, the detailed mechanisms underlying such involvement are largely unknown. In this study, a cDNA microarray containing 5,094 clones derived from a mouse dopamine cDNA library was used to determine the mitochondrial pathways involved in the neuron’s adaptation to chronic nicotine exposure. Gene expression patterns were profiled for six brain regions [amygdala, hippocampus, nucleus accumbens (NA), prefrontal cortex (PFC), striatum and ventral tegment area (VTA)] of male Sprague-Dawley rats that received nicotine (3.15 mg/kg/day; expressed as the base) by continuous s.c. infusion via osmotic minipumps. Among the transcripts significantly regulated by nicotine, we identified 11, 21, 5, 10, 2 and 17 genes with defined biological functions from each of the six brain regions, respectively. Among these genes, cytochrome c oxidase subunits I, II and III, cytochrome b, and mitochondrial NADH dehydrogenases 4 and 6 were modulated in the amygdala, hippocampus, NA and PFC, but not in striatum and VTA. Considering these genes are the key components of the electron transport system (ETS) that transfers electrons from the energy-rich electron donors NADH and FADH2 to molecule oxygen in mitochondria, our results imply that the ETS was modified by chronic nicotine exposure. Moreover, because these genes were down-regulated in NA but were up-regulated in the amygdala, hippocampus and PFC, these findings suggest a regional-specific regulation of ETS. The regulation of EST implicates the change of mitochondrial function, which may result in a disturbance of energy generation, as well as the increase of ROS concentration in both mitochondria and cytoplasm. Since ROS is related to a series of cellular activities such as protein degradation, DNA damage and intracellular signaling transduction, which are known to be associated with neuron-nicotine interaction, our results provide new evidence that mitochondria plays important role in the development of ND. (Supported by NIH DA-13783).