Uring exercise, there is a blunted activity of CS (19.11 ?6.8) in comparison with NQexercised (P \ 0.01) and Q-sedentary (P \ 0.05).Discussion In the present study, we used a rat model to study the PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/26780312 effects of quercetin and exercise on both the brain redox status and mitochondrial content. Quercetin supplementation without exercise increased mitochondrial biogenesis via up-regulation of the PGC-1a and SIRT-1 pathway. We also found that the combination of quercetin with exercise decreased exercise-induced mitochondrial adaptations in the brain through a down-modulation of the PGC-1a and SIRT1 pathway also increasing the amount of oxidative420 Page 6 ofGenes Nutr (2014) 9:markers. It must be highlighted that the dose of quercetin used is quite high and, in order to reach this quantity, a 80-kg person should consume around 1 kg of onions (the richest source of quercetin). Once ingested, quercetin shows a quite extensive metabolism and it can be absorbed by the stomach (Crespy et al. 2002), but most quercetin is absorbed from the small intestine (Manach et al. 2004; Spencer 2007). In food, quercetin is present in the glycosylated forms being glucose the most frequent sugar moiety, although other sugars may also be involved. Flavonoids in general and quercetin in particular undergo an extensive phase I and phase II metabolism (Rendeiro et al. 2012). Phase I consists in deglycosylation (Spencer et al. 2004), and phase II consists of the metabolism of the resulting aglycones to glucuronides, sulfates and O-methylated forms during transfer across the small intestine (Spencer et al. 1999; 2000). Quercetin is able to cross blood rain barrier and in fact, O-methylated forms of quercetin are accumulated in significant amount in both neurons and astrocytes. (Spencer et al. 2004). The brain is not usually considered when exercise adaptations are studied. Inactivity, however, is a risk factor for many chronic disorders, regardless of age, gender, race or health status. In fact, in relation to neurological disorders, possible clinical consequences of inactivity are as follows: learning and memory impairment, Mitochondrial division inhibitor 1 web cognitive dysfunction, dementia, depression, mood and anxiety disorders and neurodegeneration (Handschin and Spiegelman 2008). Some of these neurological disorders, if not all, can be counteracted by regular moderate intensity exercise by an up-regulation of the PGC-1a gene (Handschin and Spiegelman 2008). In fact, a recent study has proved that endurance exercise increases brain mitochondrial biogenesis by increasing the transcription of the SIRT1-PGC-1a pathway (Steiner et al. 2011). Accordingly, our results suggest that 6 weeks of exercise training increases brain mitochondrial content through the transcription of both SIRT1 and PGC-1a. Quercetin, a natural polyphenolic flavonoid present in a variety of plant foods (Manach et al. 2004), is supposed to mimic exercise-induced up-regulation of the SIRT1-PGC1a pathway and mitochondrial biogenesis in the brain (Davis et al. 2009). Our data support this statement, because we have found that quercetin increases brain mitochondrial content through the activation of the SIRT1PGC-1a pathway. PGC-1a is considered the main regulator of mitochondrial biogenesis, because it interacts and co-activates some transcription factors such as peroxisome-proliferator-activated receptors (PPARs), estrogenrelated receptors (ERRs) and nuclear respiratory factors, NRF-1 and NRF-2, that govern most of mitochondrial function.