Hippocampal Insulin Signaling And Neuroprotection Mediated By Physical Exercise In Alzheimer´s Disease

Epidemiological studies indicate continuous increases in the prevalence of Alzheimer’s Disease (AD) in the next few decades. The key feature of this disease is hippocampal neurodegeneration. This structure has an important role in learning and memory. Intense research efforts have sought to elucidate neuroprotective mechanisms responsible for hippocampal integrity. Insulin signaling seems to be a very promising pathway for the prevention and treatment of AD. This hormone has been described as a powerful activator of neuronal survival. Recent research showed that reduced insulin sensitivity leads to low-grade inflammation, and both phenomena are closely related to AD genesis. Concomitantly, exercise has been shown to exert anti-inflammatory effects and to promote improvement in insulin signaling in the hippocampus, which supports neuronal survival and constitutes an interesting non-pharmacological alternative for the prevention and treatment of AD. This review examines recent advances in understanding the molecular mechanisms involved in hippocampal neuroprotection mediated by exercise23especia

Controle visual de automóveis em curvas em situação simulada: efeitos da experiência em contexto real

Dirigir é uma tarefa altamente complexa que requer sincronia entre informações adquiridas e comandos motores, sendo a visão fonte primordial de recursos para o controle do volante por parte do motorista, para que este possa fazer a manobra na quantidade correta e no momento apropriado. Simulações nem sempre preservam os aspectos relevantes do ambiente. O ponto tangente (PT), local mais interno da curva, é onde os motoristas olham em situações de curva ao conduzir um veículo durante contexto natural, e, de acordo com a literatura, este fenômeno também ocorre em situações experimentais com o uso de simuladores específicos de trânsito. Este estudo visa verificar se este comportamento se reproduz em situação simulada de videogame e como a experiência de dirigir naturalmente afeta o desempenho na simulação. Foram recrutados vinte participantes, divididos em dois grupos de dez pessoas cada, com e sem Carteira Nacional de Habilitação e todos com experiência em videogame. A tarefa foi conduzir um veículo em circuito gerado por um jogo de videogame, enquanto seus olhos, e seus respectivos movimentos, foram monitorados e gravados por sistema eye-tracker. Para análise dos dados, foi utilizado o vídeo da imagem gerada pelo videogame com a adição do cursor referente ao olhar do participante. Foram analisadas apenas as situações nas quais os participantes executavam a manobra de cada uma das onze curvas do percurso, utilizando o software ASL Results Plus (versão 1.8.2.18) para estabelecer Áreas de Interesse (AI) de 3º e 10º ao redor do ponto tangente da curva. As variáveis dependentes foram Número Total de Fixações (NF) e Duração Total das Fixações (DF). Os dados foram submetidos à análise de variância de medidas repetidas, tendo fatores grupo (HA ou NH), AI (outros 3º ou 10º) e curvas (onze curvas). Não houve efeito significativo de grupo para ambas as variáveis dependentes. Houve efeito principal de..

Interference of the assessment method in pH values of an epoxy-based cement

Introduction: Alkalinization potential is a fundamental property of endodontic epoxy-based cements containing calcium hydroxide. Studies have shown discrepant pH results for same materials at different evaluation periods. A possible reason accounting for these differences may be the assessment procedures. Objective: To evaluate the pH value of an epoxy-based cement (Sealer 26) in different periods of analysis, using two assessment methods. Material and methods: Sealer 26 was manipulated and immediately placed into polyethylene tubes (n=10, each group) and immersed in distilled water. In G1, the tubes were kept in the same water during all experiment; and in G2, the tubes were removed and placed into another flask with an equal amount of water after the pH evaluation. The pH of these solutions was measured at 24 hours, 7, 14 and 28 days. Analysis were made within the same group according to the experimental periods and between groups in each experimental period. Data were submitted to ANOVA (α = 5%) and t test, respectively. Results: For G1 and G2, all periods showed different pH values (p 0.05) and between 7 and 14 days (p > 0.05), respectively. In each period, no significant differences were observed between the groups. Conclusion: The method to obtain the pH values in different experimental periods no interfered in the final results. However, difference was observed when the results were analyzed at same group

Avaliação da capacidade de vedamento e pH do tampão apical com cimento Portland branco acrescido de radiopacificadores convencionais

The Portland cement has shown similar biological properties to calcium hydroxide, but its radiopacity is lower. Therefore, the addition of materials that minimize this deficiency should be considered. OBJECTIVE: To evaluate the apical sealing ability and pH of a white Portland cement added of several radiopacifying agents. MATERIAL AND METHODS: Forty bovine roots with incomplete apices were selected, and the foraminal openings were standardized to PM 720G bur. After the external root sealing, an apical intracanal barrier 10.0 mm thick was executed with the white Portland cement powder, pure or added of a radiopacifying agent (iodoform, zinc oxide or bismuth subnitrate), and distilled water (0.37 mL). The apical roots were immersed 24h in water in humid atmosphere, and after that they were immersed 24h in 2% Rhodamine B, under vacuum. In sequence, the roots were longitudinally sectioned, the root fragments were photographed, the images were digitalized and the apical infiltration was measured by the Image Tool program. The pH solutions were also evaluated, in 24h and 48h and 7 and 30 days. Data were submitted to Anova test. RESULTS: The zinc oxide solution has the lowest apical infiltration in relation to the other groups (p < 0.05). The pH behavior varied during the analysis, and in the period of 24h all groups showed the highest values (p < 0.05). CONCLUSION: The type of radiopacifying agent used interferes in the sealing ability of the apical barrier, and zinc oxide showed to be the most beneficial one. The pH varies according to the period of analysis, and the highest values were obtained in the first 24h (p < 0.05).O cimento Portland tem apresentado resultados biológicos similares aos do hidróxido de cálcio, porém sua radiopacidade é precária. Assim, a adição de substâncias que minimizem essa deficiência deve ser analisada. OBJETIVO: Procurou-se avaliar a capacidade de vedamento apical e pH de um tipo de cimento Portland branco, acrescido de diversos radiopacificadores encontrados no arsenal endodôntico. MATERIAL E MÉTODOS: Quarenta raízes de dentes bovinos, com ápices incompletos, tiveram as aberturas foraminais padronizadas de modo equivalente ao diâmetro da ponta da broca PM 720G. Após a impermeabilização externa radicular, um tampão apical intrarradicular, de aproximadamente 10,0 mm de espessura, foi executado com o pó do cimento Portland branco puro ou acrescido de um radiopacificador (iodofórmio, óxido de zinco ou subnitrato de bismuto), agregado a 0,37 mL de água destilada. As raízes foram mantidas por 24 horas em ambiente úmido e, após esse período, imersas em Rhodamine B, sob vácuo, por mais 24 horas. Concluída a imersão, os espécimes foram desgastados longitudinalmente, os fragmentos radiculares fotografados, as imagens digitalizadas e a infiltração apical foi medida por meio do programa Image Tools. Paralelamente, avaliou-se também o pH das associações nos períodos de 24 e 48 horas e 7 e 30 dias. Os dados obtidos foram submetidos ao teste de Anova a um critério. RESULTADOS: A associação com o óxido de zinco proporcionou menor infiltração em relação aos demais grupos (p < 0,05). O comportamento do pH dos materiais apresentou variações ao longo do tempo de análise, e no período de 24 horas sempre foram encontrados os maiores valores (p < 0,05). CONCLUSÃO: O tipo de radiopacificador interfere na capacidade de vedação apical, sendo o óxido de zinco o mais benéfico. O pH varia de acordo com o período de análise, e foram obtidos nas primeiras 24 horas os maiores valores (p < 0,05)

Immune‐endocrine responses and physical performance of master athletes during the sports season

The purpose of this study was to investigate the impact of a training season (approximately 7 months) on physiological and salivary immune‐endocrine markers in master athletes. Nine male master athletes were evaluated at the beginning of the season (M1) and a week after the main official competition at the end of the sports season (M2). The controlled variables included Maximal oxygen consumption, anthropometric, physiological, and salivary immune‐endocrine markers. Master athletes presented a reduced percentage of fat mass and increased lean body mass at the end of the season. VO2max values were similar at M1 and M2, while the maximal heart rate and lactate were lower at M2. No differences were observed in Immunoglobulin A and cortisol levels between moments, whereas testosterone levels and the testosterone/cortisol ratio were significantly lower at the end of the season. The results suggest that maintaining regular training throughout life has positive effects on body composition and improves physiological fitness. However, care should be taken to avoid fatigue as indicated by lower testosterone levels at the end of the season120455515557CAPES - Coordenação de Aperfeiçoamento de Pessoal e Nível Superior13642/13‐8; 1417/13‐

Lifelong exercise practice and immunosenescence : master athletes cytokine response to acute exercise

The study aimed to analyze the effects of aging and lifelong training on the main pro- and anti-inflammatory cytokines, and the impact of acute exercise on the expression of these cytokines. Thirty-nine participants were allocated into 3 groups: young (31.8 +/- 3.00 yrs.), middle-aged (54.2 +/- 5.9 yrs.) and master athletes (53.1 +/- 8.8 yrs.) and performed a maximal incremental test on a cycle ergometer. Blood samples were obtained before (Pre), 10 min post-exercise (Post) and 1 h post-exercise (Post 1 h). Mean VO2max was similar for master athletes and youngers and higher compared to the middle-aged group. Resting values of the IL-1 ra, IL-1 beta, IL-4, and IL-8 were higher in master athletes compared to the young and middle-aged groups (P < 0.01), while the highest values of IL-10 and IL-17 were observed for the youngers (29.49 +/- 18.00 pg/mL and 66.24 +/- 23.23 pg/mL, respectively) with the middle-aged group showing the lowest values (2.13 +/- 1.40 pg/mL). Acute exercise effects (Post) were observed for IL-1 beta in the master athletes group, IL-6 in the young group and IL-4 for both groups (P < 0.05). No Post effects were observed for the middle-age group for all cytokines. The TNF-alpha/IL-10 ratio was higher in all moments for the middle-aged (P < 0.05). In conclusion, lifelong training helps to maintain the balance of pro- and anti-inflammatory cytokines, together with IL-10 levels close to those found in young adults11517COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPES1417/13-4Firstly, the authors would like to thank all the master athletes that volunteered to participate in this study. The Faculty of Sport Sciences and Physical Education, University of Coimbra funded the study. The present manuscript was accomplished with support from CAPES, Coordination for the Improvement of Higher Education Personnel, Brazil (grants numbers 1417/13-4

Acute physical exercise increases leptin‐induced hypothalamic extracellular signal‐regulated kinase1/2 phosphorylation and thermogenesis of obese mice

The obesity is a result of energy imbalance and the increase in thermogenesis seems an interesting alternative for the treatment of this disease. The mechanism of energy expenditure through thermogenesis is tightly articulated in the hypothalamus by leptin. The hypothalamic extracellular signal‐regulated kinase‐1/2 (ERK1/2) is a key mediator of the thermoregulatory effect of leptin and mediates the sympathetic signal to the brown adipose tissue (BAT). In this context, physical exercise is one of the main interventions for the treatment of obesity. Thus, this study aimed to verify the effects of acute physical exercise on leptin‐induced hypothalamic ERK1/2 phosphorylation and thermogenesis in obese mice. Here we showed that acute physical exercise reduced the fasting glucose of obese mice and increased leptin‐induced hypothalamic p‐ERK1/2 and uncoupling protein 1 (UCP1) content in BAT ( P < 0.05). These molecular changes are accompanied by an increased oxygen uptake (VO 2) and heat production in obese exercised mice ( P < 0.05). The increased energy expenditure in the obese exercised animals occurred independently of changes in spontaneous activity. Thus, this is the first study demonstrating that acute physical exercise can increase leptin‐induced hypothalamic ERK1/2 phosphorylation and energy expenditure of obese mice1201697704CNPQ - Conselho Nacional de Desenvolvimento Científico e TecnológicoFAPESP – Fundação de Amparo à Pesquisa Do Estado De São Paulo306535/2017‐32016/18488‐8OCR

Impaired insulin signaling and spatial learning in middle-aged rats: The role of PTP1B

The insulin and Brain-Derived Neurotrophic Factor (BDNF) signaling in the hippocampus promotes synaptic plasticity and memory formation. On the other hand, aging is related to the cognitive decline and is the main risk factor for Alzheimer's Disease (AD). The Protein-Tyrosine Phosphatase 1B (PTP1B) is related to several deleterious processes in neurons and emerges as a promising target for new therapies. In this context, our study aims to investigate the age-related changes in PTP1B content, insulin signaling, beta-amyloid content, and Tau phosphorylation in the hippocampus of middle-aged rats. Young (3 months) and middle-aged (17 months) Wistar rats were submitted to Morris-water maze (MWM) test, insulin tolerance test, and molecular analysis in the hippocampus. Aging resulted in increased body weight, and insulin resistance and decreases learning process in MWM. Interestingly, the middle-aged rats have higher levels of PTP-1B, lower phosphorylation of IRS-1, Akt, GSK3 beta, mTOR, and TrkB. Also, the aging process increased Tau phosphorylation and beta-amyloid content in the hippocampus region. In summary, this study provides new evidence that aging-related PTP1B increasing, contributing to insulin resistance and the onset of the AD.Sao Paulo State Univ UNESP, Postgrad Program Movement Sci, Rio Claro, SP, BrazilUniv Estadual Campinas, UNICAMP, Sch Appl Sci, Lab Mol Biol Exercise LaBMEx, Limeira, SP, BrazilUniv Estadual Campinas, UNICAMP, Sch Appl Sci, Lab Nutr Genom LabGeN, Limeira, SP, BrazilUniv Sao Paulo, Sch Phys Educ & Sport Ribeirao Preto, Ribeirao Preto, SP, BrazilCatholic Univ Ctr Unisalesiano, Dept Phys Educ, Lins, SP, BrazilSao Paulo Fed Univ UNIFESP, Dept Biosci, Santos, SP, BrazilUniv Estadual Campinas, OCRC, Lab Cell Signaling, Campinas, SP, BrazilUniv Estadual Campinas, UNICAMP, Sch Appl Sci, CEPECE Ctr Res Sport Sci, Limeira, SP, BrazilSao Paulo Fed Univ UNIFESP, Dept Biosci, Santos, SP, BrazilWeb of Scienc

Acute physical exercise increases APPL1/PI3K signaling in the hypothalamus of lean mice

Adiponectin is an adipokine that acts in the control of energy homeostasis. The adaptor protein containing the pleckstrin homology domain, phosphotyrosine-binding domain, and leucine zipper motif 1 (APPL1) is a key protein in the adiponectin signaling. The APPL1 mediates a positive effect on the insulin signaling through the interaction with the phosphoinositide 3-kinase (PI3K). Thus, the present study aimed to explore the effects of an acute physical exercise session on the hypothalamic adiponectin signaling. Firstly, using bioinformatics analysis, we found a negative correlation between hypothalamic APPL1 mRNA levels and food consumption in several strains of genetically diverse BXD mice. Also, the mice and the human database revealed a positive correlation between the levels of APPL1 mRNA and PI3K mRNA. At the molecular level, the exercised mice showed increased APPL1 and PI3K (p110) protein contents in the hypothalamus of Swiss mice. Furthermore, the exercise increases co-localization between APPL1 and PI3K p110 predominantly in neurons of the arcuate nucleus of hypothalamus (ARC). Finally, we found an acute exercise session reduced the food intake 5 hr after the end of fasting. In conclusion, our results indicate that physical exercise reduces the food intake and increases some proteins related to adiponectin pathway in the hypothalamus of lean mice50731813190CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP306535/2017-32016/18488-