Background: Regular physical activity practice is considered an important factor in the population's health and quality of life promotion. In order to evaluate a population's physical activity level (PAL), many instruments are used, among them the IPAQ (International Physical Activity Questionnaire). Objectives: To evaluate the PAL of Physical Education (PE) undergraduate students concerning gender and study year as well as to compare the PAL of these students with others from different health/ biology courses. Methods: Two hundred and eighty subjects; being 194 PE students (100 men and 94 women) and 86 students (17 men and 69 women) of other courses (Pharmacy; Biochemistry, Dentistry and Biology). The instrument used to measure the PAL was the IPAQ in its short version. Results: Among the PE students, it was found that 92% of them were classified as active or very active; however, there was no significant difference (p > 0,05) between male and female groups. Concerning the other courses, it was observed that the female sample is less physically active than the male one (p < 0,05). Considering the whole group in the category Active/ Very Active, the Biology (86,9%) and PE students (90%) were classified as more active than the Biochemistry (56%) and Dentistry (61,1%) ones. However, there was no significant difference (p > 0,05). Conclusions: Generally, male students have a higher level of physical activity than female ones; the undergraduate students did not show similar patterns of PAL and this level remains constant during the PE course.

Maternal undernutrition increases the risk of adult arterial hypertension. The present study investigated the short-and long-term effects of a maternal low-protein diet on respiratory rhythm, O 2 /CO 2 chemosensitivity and arterial blood pressure (ABP) of the offspring. Male Wistar rats were divided into two groups according to their mothers' diets during gestation and lactation: control (NP, 17 % of casein) and lowprotein (LP, 8 % of casein) groups. Direct measurements of ABP, respiratory frequency (RF), tidal volume (V T ) and ventilation (VE), as well as hypercapnia (7 % CO 2 ) and hypoxia (7 % O 2 ) evoked respiratory responses were recorded from the awake male offspring at the 30th and 90th days of life. Blood samples were collected for the analyses of protein, creatinine and urea concentrations. The LP offspring had impaired body weight and length throughout the experiment. At 30 d of age, the LP rats showed a reduction in the concentrations of total serum protein (approximately 24 %). ABP in the LP rats was similar to that in the NP rats at 30 d of age, but it was 20 % higher at 90 d of age. With respect to ventilatory parameters, the LP rats showed enhanced RF (approximately 34 %) and VE (approximately 34 %) at 30 d of age, which was associated with increased ventilatory responses to hypercapnia (approximately 21 % in VE) and hypoxia (approximately 82 % in VE). At 90 d of age, the VE values and CO 2 /O 2 chemosensitivity of the LP rats were restored to the control range, but the RF values remained elevated. The present data show that a perinatal LP diet alters respiratory rhythm and O 2 /CO 2 chemosensitivity at early ages, which may be a predisposing factor for increased ABP at adulthood.

The emergence of life-threatening zoonotic diseases caused by betacoronavirus, including the ongoing COVID-19 pandemic, has highlighted the need for developing preclinical models mirroring respiratory and systemic pathophysiological manifestations seen in infected humans. Here, we showed that C57BL/6J wild-type mice intranasally inoculated with the murine betacoronavirus MHV-3 develop a robust inflammatory response leading to acute lung injuries, including alveolar edema, hemorrhage, and fibrin thrombi. Although such histopathological changes seemed to resolve as the infection advanced, they efficiently impaired the respiratory function, as the infected mice displayed restricted lung distention and increased respiratory frequency and ventilation. Following respiratory manifestation, the MHV-3 infection became systemic and a high virus burden could be detected in multiple organs alongside with morphological changes. The systemic manifestation of MHV-3 infection was also marked by a sharp drop in the number of circulating platelets and lymphocytes, besides the augmented concentration of the pro-inflammatory cytokines IL-1β, IL-6, IL-12, IFN-γ, and TNF, thereby mirroring some clinical features observed in moderate and severe cases of COVID-19. Importantly, both respiratory and systemic changes triggered by MHV-3 infection were greatly prevented by blocking TNF signaling, either via genetic or pharmacologic approaches. In line, TNF blockage also diminished the infection-mediated release of pro-inflammatory cytokines and virus replication of human epithelial lung cells infected with SARS-CoV-2. Collectively, results show that MHV-3 respiratory infection leads to a large range of clinical manifestations in mice and may constitute an attractive, lower cost, biosafety level-2 in vivo platform for evaluating the respiratory and multi-organ involvement of betacoronavirus infections. Importance Mouse models have long been used as valuable in vivo platforms to investigate the pathogenesis of viral infections and effective countermeasures. The natural resistance of mice to the novel betacoronavirus SARS-CoV-2, the causative agent of COVID-19, has launched a race towards the characterization of SARS-CoV-2 infection in other animals (e.g. hamsters, cats, ferrets, bats, and monkeys) as well as the adaptation of the mouse model, by either modifying the host or the virus. In the present study, we utilized the natural pathogen of mice MHV as a prototype to model betacoronavirus-induced acute lung injure and multi—organ involvement under biosafety level 2 condition. We showed that C57BL/6J mice intranasally inoculated with MHV-3 develops a severe disease which includes acute lung damage and respiratory distress preceding systemic inflammation and death. Accordingly, the proposed animal model may provide a useful tool for studies regarding betacoronavirus respiratory infection and related diseases.

We assessed the role of NK-1 receptors (NK1R) expressing neurons in the locus coeruleus (LC) on cardiorespiratory responses to hypercapnia. To this end, we injected substance P-saporin conjugate (SP-SAP) to kill NK-1 immunoreactive (NK1R-ir) neurons or SAP alone as a control. Immunohistochemistry for NK1R, tyrosine hydroxylase (TH-ir) and Glutamic Acid Decarboxylase (GAD-ir) were performed to verify if NK1R-expressing neurons, catecholaminergic and/or GABAergic neurons were eliminated. A reduced NK1R-ir in the LC (72%) showed the effectiveness of the lesion. SP-SAP lesion also caused a reduction of TH-ir (66%) and GABAergic neurons (70%). LC SP-SAP lesion decreased by 30% the ventilatory response to 7% CO(2) and increased the heart rate (fH) during hypercapnia but did not affect MAP. The present data suggest that different populations of neurons (noradrenergic, GABAergic, and possibly others) in the LC express NK1R modulating differentially the hypercapnic ventilatory response, since catecholaminergic neurons are excitatory and GABAergic ones are inhibitory. Additionally, NK1R-ir neurons in the LC, probably GABAergic ones, seem to modulate fH during CO(2) exposure, once our previous data demonstrated that catecholaminergic lesion does not affect this variable.

Exposure to elevated concentrations of CO or hypoxia has been widely used in psychiatric research as a panic provoking stimulus. However, the use of these respiratory challenges to model panic-like responses in experimental animals has been less straightforward. Little data is available, from behavioral and endocrine perspectives, to support the conclusion that a marked aversive situation, such as that experienced during panic attacks, was evoked in these animals. We here compared the behavioral responses of male CB57BL/6 mice during exposure to 20% CO or 7% O and its consequence on plasma levels of corticosterone. We also evaluated whether clinically-effective panicolytic drugs affect the behavioral responses expressed during CO exposure. The results showed that whereas hypoxia caused a marked reduction in locomotion, inhalation of CO-enriched air evoked an active escape response, characterized by bouts of upward leaps directed to the border of the experimental cage, interpreted as escape attempts. Corticosterone levels were increased 30min after either of the respiratory challenges used, but it was higher in the hypoxia group. Chronic (21days), but not acute, treatment with fluoxetine or imipramine (5, 10 or 15mg/kg) or a single injection of alprazolam (0.025, 0.05 or 0.1mg/kg), but not of the anxiolytic diazepam (0.025, 0.05 or 0.1 and 1mg/kg) reduced the number of escape attempts, indicating a panicolytic-like effect. Altogether, the results suggest that whereas hypoxia increased anxiety, exposure to 20% CO evoked a panic-like state. The latter condition/test protocol seems to be a simple and validated model for studying in mice pathophysiological mechanisms and the screening of novel drugs for panic disorder.

Serotonergic (5-HT) neurons in the nucleus raphe obscurus (ROb) are involved in the respiratory control network. However, it is not known whether ROb 5-HT neurons play a role in the functional interdependence between central and peripheral chemoreceptors. Therefore, we investigated the role of ROb 5-HT neurons in the ventilatory responses to CO₂ and their putative involvement in the central-peripheral CO₂ chemoreceptor interaction in unanaesthetised rats. We used a chemical lesion specific for 5-HT neurons (anti-SERT-SAP) of the ROb in animals with the carotid body (CB) intact or removed (CBR). Pulmonary ventilation (V (E)), body temperature and the arterial blood gases were measured before, during and after a hypercapnic challenge (7% CO₂). The lesion of ROb 5-HT neurons alone (CB intact) or the lesion of 5-HT neurons of ROb+CBR did not affect baseline V (E) during normocapnic condition. Killing ROb 5-HT neurons (CB intact) significantly decreased the ventilatory response to hypercapnia (p < 0.05). The reduction in CO₂ sensitivity was approximately 15%. When ROb 5-HT neurons lesion was combined with CBR (anti-SERT-SAP+CBR), the V (E) response to hypercapnia was further decreased (-31.2%) compared to the control group. The attenuation of CO₂ sensitivity was approximately 30%, and it was more pronounced than the sum of the individual effects of central (ROb lesion; -12.3%) or peripheral (CBR; -5.5%) treatments. Our data indicate that ROb 5-HT neurons play an important role in the CO₂ drive to breathing and may act as an important element in the central-peripheral chemoreception interaction to CO₂ responsiveness.

The aim of this study was to examine how estrous cycle, ovariectomy, and hormonal replacement affect the respiratory [ventilation (V̇e), tidal volume, and respiratory frequency], metabolic (V̇o2), and thermoregulatory (body temperature) responses to hypercapnia (7% CO2) in female Wistar rats. The parameters were measured in rats during different phases of the estrous cycle, and also in ovariectomized (OVX) rats supplemented with 17β-estradiol (OVX+E2), with a combination of E2 and progesterone (OVX+E2P), or with corn oil (OVX+O, vehicle). All experiments were conducted on day 8 after ovariectomy. The intact animals did not present alterations during normocapnia or under hypercapnia in V̇e, tidal volume, respiratory frequency, V̇o2, and V̇e/V̇o2 in the different phases of the estrous cycle. However, body temperature was higher in female rats on estrus. Hormonal replacement did not change the ventilatory, thermoregulatory, or metabolic parameters during hypercapnia, compared with the OVX animals. Nevertheless, OVX+E2, OVX+E2P, and OVX+O presented lower hypercapnic ventilatory responses compared with intact females on the day of estrus. Also, rats in estrus showed higher V̇e and V̇e/V̇o2 during hypercapnia than OVX animals. The data suggest that other gonadal factors, besides E2 and P, are possibly involved in these responses.

Central chemoreception, the detection of CO 2 /H + within the brain and the resultant effect on ventilation, was initially localized at two areas on the ventrolateral medulla, one rostral (rVLMMitchell's) the other caudal (cVLM-Loeschcke's), by surface application of acidic solutions in anesthetized animals. Focal dialysis of a high CO 2 /H + artificial cerebrospinal fluid (aCSF) that produced a milder local pH change in unanesthetized rats (like that with a ~6.6 mm Hg increase in arterial P CO 2 ) delineated putative chemoreceptor regions for the rVLM at the retrotrapezoid nucleus and the rostral medullary raphe that function predominantly in wakefulness and sleep, respectively. Here we ask if chemoreception in the cVLM can be detected by mild focal stimulation and if it functions in a state dependent manner. At responsive sites just beneath Loeschcke's area, ventilation was increased by, on average, 17% (P < 0.01) only in wakefulness. These data support our hypothesis that central chemoreception is a distributed property with some sites functioning in a state-dependent manner.