Brain serotonin and dopamine are neurotransmitters related to fatigue, a feeling that leads to reduced intensity or interruption of physical exercises, thereby regulating performance. The present review aims to present advances on the understanding of fatigue, which has recently been proposed as a defense mechanism instead of a “physiological failure” in the context of prolonged (aerobic) exercises. We also present recent advances on the association between serotonin, dopamine and fatigue. Experiments with rodents, which allow direct manipulation of brain serotonin and dopamine during exercise, clearly indicate that increased serotoninergic activity reduces performance, while increased dopaminergic activity is associated with increased performance. Nevertheless, experiments with humans, particularly those involving nutritional supplementation or pharmacological manipulations, have yielded conflicting results on the relationship between serotonin, dopamine and fatigue. The only clear and reproducible effect observed in humans is increased performance in hot environments after treatment with inhibitors of dopamine reuptake. Because the serotonergic and dopaminergic systems interact with each other, the serotonin-to-dopamine ratio seems to be more relevant for determining fatigue than analyzing or manipulating only one of the two transmitters. Finally, physical training protocols induce neuroplasticity, thus modulating the action of these neurotransmitters in order to improve physical performance.

There is a growing consensus that the balance between the persistence of infection and the host immune response is crucial for chronification of Chagas heart disease. Extrapolation for chagasic megacolon is hampered because research in humans and animal models that reproduce intestinal pathology is lacking. The parasite-host relationship and its consequence to the disease are not well-known. Our model describes the temporal changes in the mice intestine wall throughout the infection, parasitism, and the development of megacolon. It also presents the consequence of the infection of primary myenteric neurons in culture with Trypanosoma cruzi (T. cruzi). Oxidative neuronal damage, involving reactive nitrogen species induced by parasite infection and cytokine production, results in the denervation of the myenteric ganglia in the acute phase. The long-term inflammation induced by the parasite's DNA causes intramuscular axonal damage, smooth muscle hypertrophy, and inconsistent innervation, affecting contractility. Acute phase neuronal loss may be irreversible. However, the dynamics of the damages revealed herein indicate that neuroprotection interventions in acute and chronic phases may help to eradicate the parasite and control the inflammatory-induced increase of the intestinal wall thickness and axonal loss. Our model is a powerful approach to integrate the acute and chronic events triggered by T. cruzi, leading to megacolon.

This study examined the effects of precooling on performance and pacing during 30-km cycling exercise in hot and temperate environments. 8 trained male cyclists performed 4 trials involving either cooling (PREC_TEMP and PREC_HOT) or no-cooling interventions (TEMP and HOT) prior to a 30-km self-paced cycling exercise in either a hot (35°C, 68% relative humidity) or temperate environment (24°C, 68% relative humidity). Exercise time was longer in HOT (60.62±3.47 min) than in TEMP (58.28±3.30 min; P<0.001), and precooling attenuated this thermal strain performance impairment (PREC_HOT 58.28±3.30 min; P=0.048), but it was still impaired compared with TEMP (P=0.02). Exercise performance in PREC_TEMP (54.58±4.35 min) was no different from TEMP. Initial power output was sustained until the end of the exercise in both TEMP and PREC_TEMP, but was reduced from the 12^th km until the end of the trial in HOT (P<0.05). This reduction was delayed by precooling because power output was reduced only after the 20^th km during PREC_HOT (P<0.05). Heart rate was similar in all conditions throughout almost the entire exercise, suggesting the maintenance of similar relative intensities. In conclusion, precooling was effective in attenuating, but not completely reversing thermal strain performance impairment and offered no ergogenic effect in the temperate environment.