Efeito neuroprotetor do exercício de natação e do disseleneto de m-trifluormetil difenila em um modelo de dieta hipercalórica em camundongos jovens

Abstract

The nutrition transition process has generated negative impacts on population health. The increasing consumption of foods and beverages with higher energy density and lower nutritional value promotes damage to the body, including cognitive functions. Therapeutic strategies to control and or prevent injuries induced by excessive consumption of high-calorie foods are necessary. Aerobic exercise is a non-pharmacological strategy that shows positive effects on oxidant status and cognitive function in models of neurodegenerative diseases. m-Trifluoromethyl-diphenyl diselenide (m-CF3-PhSe)2 is a low-toxicity organoselenium compound with anti-inflammatory and anti-apoptotic properties in the central nervous system. This thesis aimed to evaluate the swimming exercise and (m-CF3-PhSe)2 effects on the memory of young mice exposed to a high-calorie diet, elucidating the possible mechanisms involved in the neuroprotective action of both therapies. Initially, both in the article and manuscript male Swiss mice (21 postnatal days) were exposed to a high-calorie diet supplemented with 20% lipids + 20% carbohydrate for 28 days (CEUA: 7134140318 – 8990220420). The article results demonstrate that the moderate-intensity swimming exercise performed for 28 days protected against impairments of spatial, location, and recognition memories in young mice fed a high-calorie diet. A decrease in oxidative stress and the modulation of the Keap1/Nrf2/HO-1 pathway were found in the hippocampus of exercised mice exposed to a high-calorie diet. Swimming exercise modulated the hippocampal levels of mtTFA protein. The positive modulation of Keap1/Nrf2/HO-1 and mtTFA proteins contributed to the swimming exercise effects on behavioral memory tests. The manuscript results reveal that (m-CF3-PhSe)2, at a dose of 5 mg/kg for 7 days (intragastric route), improved location and recognition memory in young mice exposed to a high-calorie diet. (m-CF3-PhSe)2 anti-inflammatory effects were demonstrated by decreasing the hippocampal IL-1β, COX-2, and GFAP protein levels, which were increased after exposure to a high-calorie diet (m-CF3-PhSe)2 modulated the MAPK pathways by decreasing the levels of p38, JNK, and ERK phosphorylation. Besides, (m-CF3-PhSe)2 restored the increase in the levels of apoptotic proteins Bax and cleaved PARP and the decrease in the anti-apoptotic protein Bcl-2 in the hippocampus of young mice exposed to a high-calorie diet. Both therapies were effective against fatty tissue accumulation caused by exposure to a high-calorie diet. In conclusion, this thesis help to understanding how neuroprotective mechanisms contribute to swimming exercise and (m-CF3-PhSe)2 positive effects on memory of mice exposed to a high-calorie diet. Thus, both therapies are possible strategies (non-pharmacological and pharmacological) to treat memory damage caused by a high-calorie diet.