Significant modulation of mitochondrial electron transport system by nicotine in various rat brain regions

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, using a microarray consisting of 4,793 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 7 days 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.

Substance-specific and shared transcription and epigenetic changes in the human hippocampus chronically exposed to cocaine and alcohol

“…The impact of cocaine exposure on mitochondrial functions reflects changes in expression of nuclear chromosomal genes, but it is unknown whether these changes resulted from direct toxic effects on mitochondrial inner membrane components or more indirect effects of mitochondrial toxicity, or on neural networks. Interestingly, changes in expression of genes related to mitochondrial functions were also observed in nicotine-exposed rats (23). However, we did not observe similar changes after alcohol exposure.…”

Gene Expression in the Addicted Brain

“…These findings were also highly consistent with previous brain imaging studies that have revealed negative effects of cocaine on brain glucose metabolism (London et al, 1990; Lyons, Friedman, Nader, & Porrino, 1996; Macey, Rice, Freedland, Whitlow, & Porrino, 2004; Thanos, Michaelides, Benveniste, Wang, & Volkow, 2008). Furthermore, alteration of certain genes encoding for mitochondrial components induced by cocaine (Lehrmann et al, 2003) and nicotine (Wang, Kim, Donovan, Becker, & Li, 2009) exposure had also been reported previously.…”

The genetic epidemiology of substance use disorder: A review

“…Additionally, these studies suggest that acute early-stage drug use is associated with expression changes in acute early response genes (Vaccarino, Hayward, Nestler, Duman, & Tallman, 1992). In comparison, chronic substance exposure has been associated with widespread changes in expression of genes related to several diverse and fundamental cellular functions, including ion transport, chromosome remodelling, stress and immune response, cell adhesion, cell cycle, apoptosis, protein and lipid metabolism, and mitochondrial functions (Liu, Chen, Lerner, Brackett, & Matsumoto, 2005; Schroeder et al, 2008; Vilar et al, 2006; J. Wang, Kim, Donovan, Becker, & Li, 2009; Zhao et al, 2006).…”