Anxiolytic effect of alamandine in male transgenic rats with low brain angiotensinogen is dependent on activation of MrgD receptors.

Alamandine is a peptide hormone belonging to the renin-angiotensin system (RAS). It acts through the Mas-related G-protein coupled receptor type D, MrgD, which is expressed in different tissues, including the brain. In the present study, we hypothesize that a lack of alamandine, through MrgD, could cause the anxiety-like behavior in transgenic rats with low brain angiotensinogen [TGR(ASrAOGEN)680]. Adult male transgenic rats exhibited a significant increase in the latency to feeding time in the novelty suppressed feeding test and a decrease in the percentage of time and entries in the open arms in the elevated plus maze. These effects were reversed by intracerebroventricular infusion of alamandine. Pretreatment with D-Pro7-Ang-(1-7), a Mas and MrgD receptor antagonist, prevented the anxiolytic effects induced by this peptide. However, its effects were not altered by the selective Mas receptor antagonist, A779. In conclusion, our data indicates that alamandine, through MrgD, attenuates anxiety-like behavior in male TGR(ASrAOGEN)680, which reinforces the importance of the counter-regulatory RAS axis as promising target for the treatment of neuropsychiatric disorders.

Respiratory activity during seizures induced by pentylenetetrazole.

This study investigated the respiratory activity in adult Wistar rats across different behavioral seizure severity induced by pentylenetetrazole (PTZ). Animals underwent surgery for electrodes implantation, allowing simultaneous EEG and diaphragm EMG (DIAEMG) recordings and the respiratory frequency and DIAEMG amplitude were measured. Seizures were acutely induced through PTZ injection and classified based on a pre-established score, with absence-like seizures (spike wave discharge (SWD) events on EEG) representing the lowest score. The respiratory activity was grouped into the different seizure severities. During absence-like and myoclonic jerk seizures, the breathing frequency decreased significantly (∼50% decrease) compared to pre- and post-ictal periods. Pronounced changes occurred with more severe seizures (clonic and tonic) with periods of apnea, especially during tonic seizures. Apnea duration was significantly higher in tonic compared to clonic seizures. Notably, during PTZ-induced tonic seizures the apnea events were marked by tonic DIAEMG contraction (tonic-phase apnea). In the majority of animals (5 out of 7) this was a fatal event in which the seizure-induced respiratory arrest preceded the asystole. In conclusion, we provide an assessment of the respiratory activity in the PTZ-induced acute seizures and showed that breathing dysfunction is more pronounced in seizures with higher severity.

In-depth characterization of congenital Zika syndrome in immunocompetent mice: Antibody-dependent enhancement and an antiviral peptide therapy.

BACKGROUND: Zika virus (ZIKV) infection during pregnancy may cause major congenital defects, including microcephaly, ocular, articular and muscle abnormalities, which are collectively defined as Congenital Zika Syndrome. Here, we performed an in-depth characterization of the effects of congenital ZIKV infection (CZI) in immunocompetent mice. METHODS: Pregnant dams were inoculated with ZIKV on embryonic day 5.5 in the presence or absence of a sub-neutralizing dose of a pan-flavivirus monoclonal antibody (4G2) to evaluate the potential role of antibody-dependent enhancement phenomenon (ADE) during short and long outcomes of CZI. FINDINGS: ZIKV infection induced maternal immune activation (MIA), which was associated with occurrence of foetal abnormalities and death. Therapeutic administration of AH-D antiviral peptide during the early stages of pregnancy prevented ZIKV replication and death of offspring. In the post-natal period, CZI was associated with a decrease in whole brain volume, ophthalmologic abnormalities, changes in testicular morphology, and disruption in bone microarchitecture. Some alterations were enhanced in the presence of 4G2 antibody. INTERPRETATION: Our results reveal that early maternal ZIKV infection causes several birth defects in immunocompetent mice, which can be potentiated by ADE phenomenon and are associated with MIA. Additionally, antiviral treatment with AH-D peptide may be beneficial during early maternal ZIKV infection. FUND: This work was supported by the Brazilian National Science Council (CNPq, Brazil), Minas Gerais Foundation for Science (FAPEMIG), Funding Authority for Studies and Projects (FINEP), Coordination of Superior Level Staff Improvement (CAPES), National Research Foundation of Singapore and Centre for Precision Biology at Nanyang Technological University.

Swim training attenuates oxidative damage and promotes neuroprotection in cerebral cortical slices submitted to oxygen glucose deprivation.

Although it is well known that regular exercise may promote neuroprotection, the mechanisms underlying this effect are still not fully understood. We investigated if swim training promotes neuroprotection by potentiating antioxidant pathways, thereby decreasing the effects of oxidative stress on glutamate and nitric oxide release. Male Wistar rats (n=36) were evenly randomized into a trained group (TRA) (5 days/week, 8 weeks, 30 min) and a sedentary group (SED). Forty-eight hours after the last session of exercise, animals were killed and brain was collected for in vitro ischemia. Cortical slices were divided into two groups: a group in which oxidative stress was induced by oxygen and glucose deprivation (OGD), and a group of non-deprived controls (nOGD). Interestingly, exercise by itself increased superoxide dismutase activity (nOGD, SED vs. TRA animals) with no effect on pro-oxidative markers. In fact, TRA-OGD slices showed lowered levels of lactate dehydrogenase when compared with SED-OGD controls, reinforcing the idea that exercise affords a neuroprotective effect. We also demonstrated that exercise decreased glutamate and nitrite release as well as lipid membrane damage in the OGD cortical slices. Our data suggest that under conditions of metabolic stress, swim training prevents oxidative damage caused by glutamate and nitric oxide release.

[Comparative analysis of the six-minute walk test in healthy children and adolescents]. / Análise comparativa do teste de caminhada de seis minutos em crianças e adolescentes saudáveis.

OBJECTIVE: To perform a comparative analysis of the six-minute walk test in healthy children and adolescents in corridors of 30.5m (100 feet) 20m (65.6 feet) in length. METHODS: We evaluated 67 participants (36 boys and 31 girls), aged 7 to 14 years old, from public schools of a city in a metropolitan area. All were submitted to four walking tests, two in each of the corridors. The variables analyzed were: walked distance, work rate, mean blood pressure, heart rate and oxygen saturation. Statistical analysis was performed using one-way ANOVA for repeated measures and significance level at p<0.05. RESULTS: The comparison between the tests in each corridor and between the best tests in the different corridors did not show significant differences in the blood pressure, heart rate and oxygen saturation. The walked distance was not statistically different in the two tests on each corridor. However, the participants covered greater distances on the 30.5m corridor (p<0.05) compared to the best test between corridors. However, this increase was less than 10%. Regarding the cardiac overload and the work rate, there were no significant differences between the corridors. CONCLUSIONS: There were differences in walked distance between the corridors, however they were less than 10% with no significant changes in the other measured parameters. Therefore, the 20m corridor had a good reproducibility for the population of this study.

Análise comparativa do teste de caminhada de seis minutos em crianças e adolescentes saudáveis / Comparative analysis of the six-minute walk test in healthy children and adolescents

OBJETIVO: Realizar uma análise comparativa do teste de caminhada de seis minutos em crianças e adolescentes saudáveis em pistas de diferentes metragens (30,5 e 20 metros). MÉTODOS: Foram avaliados 67 voluntários de escolas públicas de uma cidade de uma região metropolitana, com idades de 7 a 14 anos, sendo 36 meninos e 31 meninas. Todos foram submetidos a quatro testes de caminhada, sendo dois em cada uma das pistas. As variáveis analisadas foram: distância caminhada, trabalho de caminhada, pressão arterial média (PAM), frequência cardíaca (FC) e saturação de oxigênio (SaO2). Para análise estatística, foi utilizado ANOVA One-Way para medidas repetidas para um p<0,05. RESULTADOS: Na comparação entre os testes realizados em cada pista e na comparação do melhor teste entre pistas, não foram observadas diferenças significativas para a PAM, FC e SaO2. A distância caminhada não foi estatisticamente diferente entre os dois testes realizados em cada pista. Entretanto, na comparação entre pistas nos testes de melhor desempenho, os voluntários caminharam distâncias significativamente maiores na pista de 30,5 metros (p<0,05). Porém, esse aumento foi inferior a 10 por cento. Quanto à sobrecarga cardíaca e ao trabalho de caminhada, não foram observadas diferenças significativas entre pistas. CONCLUSÕES: Apesar das diferenças encontradas na distância caminhada entre pistas, ela foi menor que 10 por cento sem variações importantes nos outros parâmetros avaliados. Portanto, a pista de 20 metros se adequou aos critérios de reprodutibilidade descritos na literatura para a população do presente estudo.

OBJECTIVE: To perform a comparative analysis of the six-minute walk test in healthy children and adolescents in corridors of 30.5m (100 feet) 20m (65.6 feet) in length. METHODS: We evaluated 67 participants (36 boys and 31 girls), aged 7 to 14 years old, from public schools of a city in a metropolitan area. All were submitted to four walking tests, two in each of the corridors. The variables analyzed were: walked distance, work rate, mean blood pressure, heart rate and oxygen saturation. Statistical analysis was performed using one-way ANOVA for repeated measures and significance level at p<0.05. RESULTS: The comparison between the tests in each corridor and between the best tests in the different corridors did not show significant differences in the blood pressure, heart rate and oxygen saturation. The walked distance was not statistically different in the two tests on each corridor. However, the participants covered greater distances on the 30.5m corridor (p<0.05) compared to the best test between corridors. However, this increase was less than 10 percent. Regarding the cardiac overload and the work rate, there were no significant differences between the corridors. CONCLUSIONS: There were differences in walked distance between the corridors, however they were less than 10 percent with no significant changes in the other measured parameters. Therefore, the 20m corridor had a good reproducibility for the population of this study.