Project description:Exercise exerts a wide range of beneficial effects for healthy physiology. However, the mechanisms regulating an individual's motivation to engage in physical activity remain incompletely understood. An important factor stimulating the engagement in both competitive and recreational exercise is the motivating pleasure derived from prolonged physical activity, which is triggered by exercise induced neurochemical changes in the brain. Here, we report on the discovery of a gut brain connection in mice that enhances exercise performance by augmenting dopamine signalling during physical activity. We find that microbiome dependent production of endocannabinoid metabolites in the gut stimulates the activity of TRPV1 expressing sensory neurons and thereby elevates dopamine levels in the ventral striatum during exercise. Stimulation of this pathway improves running performance, whereas microbiome depletion, peripheral endocannabinoid receptor inhibition, ablation of spinal afferent neurons or dopamine blockade abrogate exercise capacity. These findings indicate that the rewarding properties of exercise are influenced by gut derived interoceptive circuits and provide a microbiome dependent explanation for interindividual variability in exercise performance. Our study also suggests that interoceptomimetic molecules that stimulate the transmission of gut derived signals to the brain may enhance the motivation for exercise.
Project description:While moderate endurance exercise has been reported to improve cardiovascular health , its effects on cardiac structure and function are not fully characterized, especially with respect to sex dimorphism. We aimed to assess the effects of moderate endurance exercise on cardiac physiology in male versus female mice.
Project description:Exercise has the potential to significantly impact those suffering from autoimmune and inflammatory diseases including multiple sclerosis (MS). However, persons with multiple sclerosis (PwMS) do not engage in sufficient activity due to barriers such as increased fatigue, reduced mobility and disability. Characterizing the potential molecular benefits for acute exercise is critical for understanding its therapeutic effects on inflammatory lesions. Investigating the effects of exercise on the central nervous system (CNS) will help in guiding future design and implementation of programs to maximize the benefits of exercise for PwMS.
Project description:Short-term treadmill exercise does not overcome the effects of cafeteria diet on fecal microbiome while altering adipose and hypothalamic gene expression in rats
Project description:In order to assess the impact of treadmill exercise on traumatic brain injury outcomes, we subjected male and female swiss webster mice to a controlled cortical impact (CCI), followed by 10 days of sedentary, low-, moderate-, or high-intensity treadmill exercise. Outcome measures included neurometabolic function, cognitive recovery, oxidative stress, pathophysiology, and single nuclei RNA sequencing (snRNA seq). The snRNA seq study was conducted on both male and female mice, and included a total of 2 replicates (each was a pool of 2 tissue samples) from each of the following groups: male sham sedentary, male CCI sedentary, male CCI low, male CCI high, female sham sedentary, female CCI sedentary, female CCI low, female CCI high. Our data reveal exercise intensity- and sex-dependent effects of treadmill exercise following injury. Transcriptomic changes were largely limited to the low-intensity exercised CCI males.
Project description:Increased beta-cell senescence contributes to the development of type 2 diabetes (T2D). Exercise is critical in the treatment of T2D and can attenuate aging-associated cellular changes, but its effects on beta-cell senescence are unknown. Using two mouse models of insulin resistance, we showed that exercise prevented and reversed beta-cell senescence. Mechanistic studies revealed that these effects were mediated by exercise-induced increases in serum glucagon leading to AMPK activation in beta-cells. Nuclear translocation of NRF2 in mouse islets after exercise and its inversely proportional regulation of p16Ink4a, suggested its role as a molecular mediator between AMPK activation and cellular senescence.
Project description:Single nucleus RNA sequencing of mouse striatum at steady state and after exercise in mice treated and untreated with broad spectrum antibiotics.
