2011). The authors hypothesize that mitochondria may underpin a “unifying link between energy metabolism, oxidative stress, and neurotransmission alterations” that were observed between high- and low-anxiety trait mice. Third, mitochondria-targeted antioxidant SkQ1 has been associated with decreased expression of anxiety selleck chemicals llc behaviors in rats (Stefanova et al. 2010). Finally, mutant mice with reduced function of Bcl-2, a key modulator of mitochondrial function, demonstrate increased anxiety behavior (Einat et al. 2005). Exposure to cigarettes can lead to mitochondrial Inhibitors,research,lifescience,medical dysfunction (Miro et al. 1999; Anbarasi et al. 2005b),

as demonstrated by increased levels of cholesterol, lipid peroxides and increased cholesterol/phospholipid ratio, in conjunction with decreased mitochondrial enzymes in those exposed to cigarette smoke. However, chronic cigarette smoking was not associated with derangement of mitochondrial function in a separate study, but did Inhibitors,research,lifescience,medical prevent exercise-induced

improvement in mitochondrial function (Speck et al. 2011). A potential explanation for absence of demonstrable mitochondrial dysfunction in this study Inhibitors,research,lifescience,medical may relate to the use of SWISS mice in the experimental design that were demonstrated to be highly resistant to cigarette smoke-induced oxidative stress (Rueff-Barroso et al. 2010). Recent evidence suggests that nicotine exposure may worsen mitochondrial function through direct effects on membrane potential and granularity of desensitizing α7 nAChRs (Gergalova

Inhibitors,research,lifescience,medical and Skok 2011). Given these preliminary results, investigation of therapies that promote mitochondrial function in patients with anxiety disorders would be fruitful. These studies should take in account smoking status. Neurotrophins and neurogenesis Increasing Inhibitors,research,lifescience,medical evidence supports a role for NTs and neurogenesis in development of anxiety disorders and anxiety symptoms, although certain mediators may exert varying effects on different anxiety symptoms. Animal models have demonstrated stress-related changes to neurogenesis in areas associated with mood and anxiety disorders including the hippocampus (Cirulli et al. 2010). Exposure to neonatal stress can reduce expression of hippocampal BDNF via altering gene expression (Roth et al. 2009; Roth and Sweatt 2011), which may facilitate vulnerability to mood and anxiety as consequence out of decreased neuronal survival (Gomez-Pinilla and Vaynman 2005). In addition, altered levels of BDNF and their Trk B receptors may occur in dopaminergic pathways projecting from the ventral tegmental area in the midbrain to the nucleus accumbens (Yu and Chen 2011). Changes in BDNF appear associated with increased anxiety behaviors. Intrahippocampal injections of BDNF in rats lead to an increase in anxiety assessed by facilitatory avoidance and the light–dark test.