Letícia Maria de Souza Cordeiro

Inhibition of tryptophan hydroxylase abolishes fatigue induced by central tryptophan in exercising rats

Fatigue during prolonged exercise is related to brain monoamines concentrations, but the mechanisms underlying this relationship have not been fully elucidated. We investigated the effects of increased central tryptophan (TRP) availability on physical performance and thermoregulation in running rats that were pretreated with parachlorophenylalanine (p‐CPA), an inhibitor of the conversion of TRP to serotonin. On the 3 days before the experiment, adult male Wistar rats were treated with intraperitoneal (ip) injections of saline or p‐CPA. On the day of the experiment, animals received intracerebroventricular (icv) injections of either saline or TRP (20.3 μM) and underwent a submaximal exercise test until fatigue. Icv TRP‐treated rats that received ip saline presented higher heat storage rate and a 69% reduction in time to fatigue compared with the control animals. Pretreatment with ip p‐CPA blocked the effects of TRP on thermoregulation and performance. Moreover, ip p‐CPA administration accelerated cutaneous heat dissipation when compared with saline‐pretreated rats. We conclude that an elevated availability of central TRP interferes with fatigue mechanisms of exercising rats. This response is modulated by serotonergic pathways, because TRP effects were blocked in the presence of p‐CPA. Our data also support that a depletion of brain serotonin facilitates heat loss mechanisms during exercise.

Fatigue is mediated by cholinoceptors within the ventromedial hypothalamus independent of changes in core temperature

We investigated brain mechanisms modulating fatigue during prolonged physical exercise in cold environments. In a first set of studies, each rat was subjected to three running trials in different ambient temperatures (Ta). At 8 °C and 15 °C, core body temperature (Tcore) decreased and increased, respectively, whereas at 12 °C, the Tcore did not change throughout the exercise. In another set of experiments, rats were randomly assigned to receive bilateral 0.2 μL injections of 2.5 × 10−2 M methylatropine or 0.15 M NaCl solution into the ventromedial hypothalamic nuclei (VMH). Immediately after the injections, treadmill exercise was started. Each animal was subjected to two experimental trials at one of the following Ta: 5 °C, 12 °C or 15 °C. Muscarinic blockade of the VMH reduced the time to fatigue (TF) in cold environments by 35–37%. In all Ta studied, methylatropine‐treated rats did not present alterations in Tcore and tail skin temperature compared with controls. These results indicate that, below the zone of thermoneutrality, muscarinic blockade of the VMH decreases the TF, independent of changes in Tcore. In conclusion, our data suggest that VMH muscarinic transmission modulates physical performance, even when the effects of thermoregulatory adjustments on fatigue are minimal.

Intrinsic exercise capacity is related to differential monoaminergic activity in the rat forebrain.

Monoamines levels in central nervous system have been associated with exercise performance and fatigue. The present study investigated whether intrinsic exercise capacity is associated with differential activity of monoamines in the caudate-putamen (CPu) and accumbens (ACC) nucleus. Male Wistar rats were subjected to a progressive testing protocol. Based on the maximal time of exercise in the progressive testing protocol (TEPmax), the animals were divided into low-performance (LP), high-performance (HP), and standard-performance (SP) groups. After classification, eight animals in each group were chosen randomly and evaluated in two experimental situations: rest (n=8) or moderate exercise (ME) at 60% of maximal velocity (n=8). The CPu and ACC were dissected for analyses of monoamine levels. At rest, HP rats exhibited higher 3,4-dihydroxyphenylacetic acid (DOPAC)/dopamine (DA) ratio and lower serotonin (5-HT) concentration compared other groups, and lower 5-hydroxyindoleacetic (5-HIAA) compared with the LP rats. The ME resulted in increased DOPAC/DA ratio in the CPu of all experimental groups. In both the CPu and ACC, ME increased 5-HIAA levels in SP and HP rats and 5-HIAA/5-HT ratio only in HP rats. Thus, our findings demonstrate that rats with natural intrinsic differences in performance to exercise exhibit alterations in dopaminergic and serotonergic systems at rest and after ME exercise until fatigue.

Improvement of the energy supply and contractile function in normal and ischemic rat hearts by dietary orotic acid

AIMS As cardiac performance is closely related to its energy supply, our study investigated the effect of the orotic acid cardioprotective agent on the pathways of energy supply, in both conditions of normal flow and ischemia. MAIN METHODS Male Wistar rats were fed during nine days with a balanced diet only or supplemented with 1% orotic acid. KEY FINDINGS Dietary administration of orotic acid increased the cardiac utilization of fatty acids, activity of the lipoprotein lipase, expression of the gene of peroxisome proliferator-activated receptor α and its target enzymes. In addition, orotic acid increased the myocardial uptake and incorporation of glucose, glycogen content and level of GLUT4, concentration of glycolytic metabolites and lactate production in both experimental conditions, baseline and after regional ischemia. SIGNIFICANCE Thus, in orotic acid hearts there was a simultaneous stimulus of fatty acid oxidation and glycolytic pathway, reflected in increased energetic content even in pre-ischemia. The analysis of the cardiac contractility index showed a positive inotropic effect of orotic acid due, at least in part, to the increased availability of energy. The result allows us to suggest that the metabolic changes induced by orotic acid result in appreciable alterations on myocardial contractile function.

Asymmetric sympathetic output: the dorsomedial hypothalamus as a potential link between emotional stress and cardiac arrhythmias

The autonomic response to emotional stress, while involving several target organs, includes an important increase in sympathetic drive to the heart. There is ample evidence that cardiac sympathetic innervation is lateralized, and asymmetric autonomic output to the heart during stress is postulated to be a causal factor that precipitates cardiac arrhythmias. Recent animal studies provided a new picture of the central pathways involved in the cardiac sympathetic response evoked by emotional stress, pointing out a key role for the region of dorsomedial hypothalamus. However, how much of this information can be extrapolated to humans? Analysis of human functional imaging data at rest or during emotional stress shows some consistency with the components that integrate these pathways, and attention must be given to the asymmetric activation of subcortical sites. In this short review, we will discuss related findings in humans and animals, aiming to understand the neurogenic background for the origin of emotional stress-induced cardiac arrhythmias.

Estrogen therapy attenuates adiposity markers in spontaneously hypertensive rats

Ovarian hormones modulate the metabolism of adipose cells and present a protective effect against hypertension. The aim of this study was to compare the effect of estradiol on adiposity markers in spontaneously hypertensive rats. Ovariectomized spontaneously hypertensive rats treated with estradiol (5 μg/100 g/day), three weeks after ovariectomy, presented decreased blood pressure and insulin levels and increased hepatic glycogen content. Periuterine or mesenteric adipocytes from treated animals were smaller as compared to vehicle treated group, whereas no differences were observed in relation to the number of cells. Basal rates of glycerol release were higher only in periuterine adipocytes of treated rats. The increment of glycerol release over basal values in response to isoproterenol was 400% and 440%, 283% and 330% for vehicle and estradiol treated periuterine and mesenteric adipocytes, respectively. The estradiol treated group was more sensitive to insulin inhibition of isoproterenol-stimulated lipolysis than the control animals. The lipoprotein lipase activity decreased after treatment, only in periuterine adipose tissue. Estradiol administration increased basal and insulin-stimulated rates of glucose transport in adipocytes of both sites, although the values obtained by periuterine were higher than those observed for mesenteric adipocytes. Both adipose tissues from treated animals exhibited a decreased expression of the peroxisome proliferator-activated receptor-γ, but an increased expression of peroxisome proliferator-activated receptor-α in liver. These findings suggest that estrogen administration attenuates adiposity markers of spontaneously hypertensive rats as a result of the decreased expression levels of peroxisome proliferator-activated receptor-γ in adipose tissue and increased expression of peroxisome proliferator-activated receptor-α in liver.

Effects of manipulating the duration and intensity of aerobic training sessions on the physical performance of rats

This study investigated the effects of manipulating the load components of aerobic training sessions on the physical performance of rats. To achieve this purpose, adult male Wistar rats were divided into four groups: an untrained control (CON) group and training groups with a predominant overload in intensity (INT) or duration (DUR) or alternating and similar overloads in intensity and duration (ID). Prior to, during, and after 8 weeks of the control or training protocols, the performance of the rats (evaluated by their workload) was determined during fatiguing, incremental-speed treadmill running. Two additional incremental running tests were performed prior to and at the end of the protocols to measure the peak rate of oxygen consumption (VO2peak). As expected, the rats in the trained groups exhibited increased performance, whereas the untrained rats showed stable performance throughout the 8 weeks. Notably, the performance gain exhibited by the DUR rats reached a plateau after the 4th week. This plateau was not present in the INT or ID rats, which exhibited increased performance at the end of training protocol compared with the DUR rats. None of the training protocols changed the VO2peak values; however, these values were attained at faster speeds, which indicated increased running economy. In conclusion, our findings demonstrate that the training protocols improved the physical performance of rats, likely resulting from enhanced running economy. Furthermore, compared with overload in duration, overload in the intensity of training sessions was more effective at inducing performance improvements across the 8 weeks of the study.

Intrinsic exercise capacity in rats influences dopamine neuroplasticity induced by physical training

The study evaluates whether the intrinsic capacity for physical exercise influences dopamine neuroplasticity induced by physical training. Male rats were submitted to three progressive tests until fatigue. Based on the maximal time of exercise (TE), rats were considered as low performance (LP), standard performance (SP) or high performance (HP) to exercise. Eight animals from each group (LP, SP, and HP) were randomly subdivided in sedentary (SED) or trained (TR). Physical training was performed for 6 wk. After that, concentrations of dopamine (DA), serotonin (5-HT), and their metabolites and mRNA levels of D1 receptor ( Drd1), D2 receptor ( Drd2), dopamine transporter ( Dat), tyrosine hydroxylase ( Th), glia cell line neurotrophic factor ( Gdnf), and brain-derived neurotrophic factor ( Bdnf) were determined in the caudate-putamen (CPu). TE was increased with training in all performance groups. However, the relative increase was markedly higher in LP rats, and this was associated with a training-induced increase in dopaminergic activity in the CPu, which was determined by the 3,4-dihydroxyphenylacetic acid (DOPAC)/DA ratio. An opposite monoamine response was found in HP-TR rats, in which physical training decreased the DOPAC/DA ratio in the CPu. Moreover, LP-SED rats displayed higher levels of Drd2 in the CPu compared with the other SED groups, and this higher expression was decreased by physical training. Physical training also decreased Dat and increased Gdnf in the CPu of LP rats. Physical training decreased Bdnf in the CPu only in HP rats. Thus, we provide evidence that the intrinsic capacity to exercise affects the neuroplasticity of the dopaminergic system in response to physical training. NEW & NOTEWORTHY The findings reported reveal that dopaminergic neuroplasticity in caudate-putamen induced by physical training is influenced by the intrinsic capacity to exercise in rats. To evaluate the dopaminergic neuroplasticity, we analyzed mRNA levels of D1 receptor, D2 receptor, dopamine transporter, tyrosine hydroxylase, glia cell line neurotrophic factor, and brain-derived neurotrophic factor as well as concentrations of dopamine, serotonin, and their metabolites. These results expand our knowledge about the interrelationship between genetic background, physical training, and dopaminergic neuroplasticity.

Virgin coconut oil is effective to treat metabolic and inflammatory dysfunction induced by high refined carbohydrate-containing-diet in mice

The global rise in obesity rates is alarming since this condition is associated with chronic low-grade inflammation and secondary comorbidities as glucose intolerance, cardiovascular disease and liver damage. Therefore, a lot of dietary approaches are proposed to prevent and to treat obesity and its associated disorders. Virgin coconut oil (VCO) is well known as a functional food due to its significant amounts of medium-chain triglycerides. This study aimed to evaluate the effect of VCO on adiposity, metabolic and inflammatory dysfunctions induced by a high-refined carbohydrate-containing (HC) diet in mice. Male BALB/c mice were divided into two groups and fed with control (C) or HC diet to induce obesity for eight weeks. At the 9th week mice fed with HC diet were randomly regrouped into four groups, and were kept this way until the 12th week, as following: (i) HC diet alone or HC diet supplemented with three different VCO doses (ii) 1000 mg/kg, (iii) 3000 mg/kg and (iv) 9000 mg/kg. Regardless of the concentration used, VCO supplementation promoted lower adiposity and also improvement in glucose tolerance, lower serum glucose and lipid levels and decreased hepatic steatosis. Moreover, VCO intake induced a lower inflammatory response due to decreased number of leukocytes and TNF-α and IL-6 concentrations in adipose tissue, as well as reduced counts of total leukocytes, mononuclear and polymorphonuclear circulating cells. Our data showed that VCO can be considered as an interesting potential dietary approach to attenuate obesity and its metabolic and inflammatory alterations.

Rats with higher intrinsic exercise capacities exhibit greater preoptic dopamine levels and greater mechanical and thermoregulatory efficiencies while running

The present study investigated whether intrinsic exercise capacity affects the changes in thermoregulation, metabolism and central dopamine (DA) induced by treadmill running. Male Wistar rats were subjected to three incremental exercises and ranked as low-performance (LP), standard-performance (SP), and high-performance (HP) rats. In the first experiment, abdominal (TABD) and tail (TTAIL) temperatures were registered in these rats during submaximal exercise (SE) at 60% of maximal speed. Immediately after SE, rats were decapitated and concentrations of DA and 3,4-dihydroxyphenylacetic acid (DOPAC) were determined in the preoptic area (POA). In the second experiment, oxygen consumption was measured and mechanical efficiency (ME) was calculated in these rats during an incremental exercise. HP rats ran for longer periods and were fatigued with higher TABD values, with no difference in TTAIL. Nevertheless, thermoregulatory efficiency was higher in HP rats, compared with other groups. DA and DOPAC concentrations in the POA were increased by SE, with higher levels in HP compared with LP and SP rats. V̇o2 also differed between groups, with HP rats displaying a lower consumption throughout the incremental exercise but a higher V̇o2 at fatigue. ME, in turn, was consistently higher in HP than in LP and SP rats. Thus, our results show that HP rats have greater TABD values at fatigue, which seem to be related to a higher dopaminergic activity in the POA. Moreover, HP rats exhibited a greater thermoregulatory efficiency during exercise, which can be attributed to a lower V̇o2, but not to changes in tail heat loss mechanisms. NEW & NOTEWORTHY Our findings reveal that rats with higher intrinsic exercise capacities have greater thermoregulatory efficiencies and increased dopaminergic activity in the preoptic area, a key brain area in thermoregulatory control, while exercising. Moreover, higher intrinsic exercise capacities are associated with decreased oxygen consumption for a given exercise intensity, which indicates greater mechanical efficiencies. Collectively, these findings help to advance our knowledge of why some rats of a given strain can exercise for longer periods than others.