High-Intense Interval Training Prevents Cognitive Impairment And Increases The Expression Of Muscle Genes Fndc5 And Ppargc1a In A Rat Model Of Alzheimer's Disease.

BACKGROUND: Alzheimer's disease is the most common neurodegenerative disease in the world, characterized by the progressive loss of neuronal structure and function, whose main histopathological landmark is the accumulation of ß-amyloid in the brain. OBJECTIVE: It is well known that exercise is a neuroprotective factor and that muscles produce and release myokines that exert endocrine effects in inflammation and metabolic dysfunction. Thus, this work intends to establish the relationship between the benefits of exercise through the chronic training of HIIT on cognitive damage induced by the Alzheimer's model by the injection of ß amyloid 1-42. METHODS: For this purpose, forty-eight male Wistar rats were divided into four groups: Sedentary Sham (SS), Trained Sham (ST), Sedentary Alzheimer's (AS), and Trained Alzheimer's (AT). Animals were submitted to stereotactic surgery and received a hippocampal injection of Aß1-42 or a saline solution. Seven days after surgery, twelve days of treadmill adaptation followed by five maximal running tests (MRT) and fifty-five days of HIIT, rats underwent the Morris water maze test. The animals were then euthanized, and their gastrocnemius muscle tissue was extracted to analyze the Fibronectin type III domain containing 5 (FNDC5), PPARG Coactivator 1 Alpha (PPARGC1A), and Integrin subunit beta 5 (ITGB5-R) expression by qRT-PCR in addition to cross-sectional areas. RESULTS: The HIIT prevents the cognitive deficit induced by the infusion of amyloid ß 1-42 (p<0.0001), causes adaptation of muscle fibers (p<0.0001), modulates the gene expression of FNDC5 (p<0.01), ITGB5 (p<0.01) and PPARGC1A (p<0.01), and induces an increase in peripheral protein expression of FNDC5 (p<0.005). CONCLUSION: Thus, we conclude that HIIT can prevent cognitive damage induced by the infusion of Aß1-42, constituting a non-pharmacological tool that modulates important genetic and protein pathways.

Effect of involuntary chronic physical exercise on beta-amyloid protein in experimental models of Alzheimer's disease: Systematic review and meta-analysis.

The excessive deposition of ß-amyloid proteins (Aß) is directly correlated with the establishment and development of Alzheimer's Disease (AD). Current treatments for AD only reduce symptoms instead of acting on Aß, the primary etiological agent. Hence, the anti-amyloid effect of regular exercise has been widely investigated as an alternative therapy. This systematic review and meta-analysis examined the anti-amyloid effect of regular physical exercise in animal models of AD. The search was conducted on the electronic databases Pubmed, Embase, Scopus and Web of Science without data limitation and using the following describers: "amyloid beta" (OR senile plaque OR amyloid plaque) and "exercise" (OR physical activity OR training). The risk of bias was evaluated using the SYRCLE's tool. Meta-analyses were conducted using models of random continuous effects. A total of 36 studies were selected and most used: transgenic mice (n = 29), treadmill training, duration of 12 weeks (interval of 4 to 28 weeks), rate of 60 min/day (interval of 30 min and up until free access) and speed of 12 m/min (interval of 3.2 to 32 m/min). The hippocampus and cortex were the most frequently investigated regions. Meta-analysis demonstrated a decrease in Aß with greater effect in unspecified isoforms Meta-analysis demonstrated a decrease in Aß with greater effect in unspecified isoforms (N = 4; SMD = -2.71, IC 95%: -3.59, -1.84, p < 0.00001, Q2 = 3.38, I2 = 11%) and Aß1-42 (N = 21; SMD = -1.94, IC 95%: -2.37, -1.51, p < 0.00001, Q2 = 33,37, I2 = 40%). Concerning training, greater effect was found with: 1) swimming (N = 4; SMD = -1.98, IC 95%: -3,28 - -0,68, p = 0.003, Q2 = 9.74, I2 = 69%), 2) moderate intensity (N = 4; SMD = -2.03, IC 95%: -3.31 - -0.75, p < 0.005, Q2 = 12.68, I2 = 76%); 3) duration up to six weeks (N = 6; N = 6; SMD = -2.35, IC 95%: -3.15 - -1.55, p < 0.00001, Q2 = 8.38, I2 = 40%); 4) young animals (SMD = -2.00, IC 95%: -2.59 - -1.42, p < 0.00001, Q2 = 24.90, I2 = 52%); 5) in the amygdala region (N = 1; SMD = -8.56, IC 95%: -12.88 - -4.23, p = 0.0001) and females (N = 4; SMD = -2.14, IC 95%: -3.48 - -0.79, p = 0.002, Q2 = 10.31, I2 = 71%). However, the reduction of Aß was associated with decrease of amyloidogenic pathway and increase of non-amyloidogenic. Hence, regular physical exercise demonstrated anti-amyloid effect in experimental models of AD through positive alterations in APP processing through different signaling pathways.

Neuroprotective mechanisms of chronic physical exercise via reduction of ß-amyloid protein in experimental models of Alzheimer's disease: A systematic review.

AIMS: Alzheimer's disease (AD) is the most common irreversible chronic neurodegenerative disease. It is characterized by the abnormal accumulation of ß-amyloid protein (Aß), which triggers homeostatic breakage in several physiological systems. However, the effect of chronic exercise on the formation of Aß as an alternative therapy has been investigated. This systematic review examines the antiamyloid effect of different types and intensities of exercise, seeking to elucidate its neuroprotective mechanisms. MAIN METHODS: The research was conducted in the electronic databases Pubmed, Embase, Scopus and Web of Science, using the following descriptors: "amyloid beta" (OR senile plaque OR amyloid plaque) and "exercise" (OR physical activity OR training). The risk of bias was evaluated through SYRCLE's Risk of Bias for experimental studies. KEY FINDINGS: 2268 articles were found, being 36 included in the study. A higher frequency of use of mice with genetic alterations was identified for the Alzheimer's disease (AD) model (n = 29). It was used as chronic training: treadmill running (n = 24), voluntary running wheel (n = 7), swimming (n = 4) and climbing (n = 2). The hippocampus and the cortex were the most investigated regions. However, physiological changes accompanied by the reduction of Aß and associated with AD progression were verified. It is concluded that exercise reduces the production of Aß in models of animals with AD. SIGNIFICANCE: Nevertheless, this effect contributes to the improvement of several physiological aspects related to Aß and that contribute to neurological impairment in AD.

Duathlon training model adapted for female rats: blood glucose-lactate correlations / Modelo de treinamento de duathlon adaptado para ratas: correlação de glicose-lactato no sangue / Modelo de entrenamiento de duatlón adaptado para ratones: correlación de glucosa-lactato en la sangre

ABSTRACT Objective: To propose a duathlon model adapted for rats (associated swimming and running training) and compare it with the individual activities carried out separately, considering the glucose uptake and serum lactate production mechanism. Methods: Twenty-eight 90-day-old Wistar rats with a mean weight of 150-200 g were used. The animals were divided into four groups: control group, swimming group, running group, and swimming/running group. These animals were adapted to their respective training programs for three days and underwent the 4-week training protocol soon afterwards. Pre- and post-training blood lactate and blood glucose analyses were performed at the end of each week. Statistical difference was considered when the p value was less than 0.01 (p <0.01). Results: There was a decrease in glycemic levels and an increase in lactate levels in the swimming and swimming/running groups throughout the training period, which did not occur in the running group. Conclusion: The duathlon model adapted for rats proved satisfactory in terms of the production and stabilization of blood lactate levels. Level of evidence II; Therapeutic Studies - Investigating the Results of Treatment.

RESUMO Objetivo: Propor um modelo de duathlon adaptado para ratos (treinamento associado de natação e corrida) e compará-lo com as modalidades praticadas isoladamente, considerando o mecanismo de consumo de glicose e produção de lactato sérico. Métodos: Foram utilizados vinte e oito ratos Wistar, com 90 dias de vida e peso médio de 150-200 g. Os animais foram divididos em quatro grupos: grupo controle, grupo de natação, grupo de corrida e grupo de natação/corrida. Esses foram adaptados aos seus respectivos treinos durante três dias e, logo depois, foram submetidos ao protocolo de treinamento com duração de quatro semanas. No final de cada semana, foram realizadas análises de lactato e glicose sanguínea pré- e pós- treinamento. A diferença estatística foi considerada quando o valor p era inferior a 0,01 (p <0,01). Resultados: Houve diminuição nos níveis de glicemia e aumento nos níveis de lactato nos grupos de natação e natação/corrida ao longo do período de treinamento, o que não ocorreu no grupo de corrida. Conclusão: Pode-se verificar que o modelo duathlon adaptado para ratos foi satisfatório em relação à produção e estabilização dos níveis sanguíneos de lactato. Nível de evidência II; Estudos terapêuticos - Investigação dos resultados de tratamento.

RESUMEN Objetivo: Proponer un modelo de duatlón adaptado para ratones (entrenamiento asociado de natación y carrera) y compararlo con las modalidades practicadas aisladamente, considerando el mecanismo de consumo de glucosa y producción de lactato sérico. Métodos: Fueron utilizados veintiocho ratones Wistar, con 90 días de vida y peso promedio de 150-200 g. Los animales fueron divididos en cuatro grupos: grupo control, grupo de natación, grupo de carrera y grupo de natación/carrera. Esos fueron adaptados a sus respectivos entrenamientos durante tres días y, luego después, fueron sometidos al protocolo de entrenamiento con duración de cuatro semanas. Al final de cada semana, fueron realizados análisis de lactato y glucosa sanguínea pre y post entrenamiento. La diferencia estadística fue considerada cuando el valor p era inferior a 0,01 (p <0,01). Resultados: Hubo disminución en los niveles de glucemia y aumento en los niveles de lactato en los grupos de natación y natación/carrera a lo largo del período de entrenamiento, lo que no ocurrió en el grupo de carrera. Conclusión: Se puede verificar que el modelo duatlón adaptado para ratones fue satisfactorio con relación a la producción y estabilización de los niveles sanguíneos de lactato. Nivel de evidencia II; Estudios terapéuticos - Investigación de los resultados del tratamento.