Abstract
Despite the active research in this field, molecular mechanisms underlying exercise-induced beneficial effects on brain physiology and functions are still matter of debate, especially with regard to biological processes activated by regular exercise affecting the onset and progression of hippocampal aging in individuals unfamiliar with habitual physical activity. Since such responses seem to be mediated by changes in antioxidative, antiglycative and metabolic status, a possible exercise-induced coordinated response involving redox, methylglyoxal- and sirtuin-related molecular networks may be hypothesized. In this study, hippocampi of CD1 mice undergoing the transition from mature to middle age were analyzed for redox-related profile, oxidative and methylglyoxal-dependent damage patterns, energy metabolism, sirtuin1 and glyoxalase1 expression after a 2- or 4-mo treadmill running program. Our findings suggested that the 4-mo regular running lowered the chance of dicarbonyl and oxidative stress, activated mitochondrial catabolism and preserved sirtuin1-related neuroprotection. Surprisingly, the same cellular pathways were negatively affected by the first 2 months of exercise, thus showing an interesting biphasic response. In conclusion, the duration of exercise caused a profound shift in the response to regular running within the rodent hippocampus in a time-dependent fashion. This research revealed important details of the interaction between exercise and mammal hippocampus during the transition from mature to middle age, and this might help to develop non-pharmacological approaches aimed at retarding brain senescence, even in individuals unfamiliar with habitual exercise.
Highlights
IntroductionExercise promotes Reactive oxygen species (ROS) overproduction [7,8], regular and moderate exercise paradigms improve psycho-physical functions, retards aging and lowers the risk of developing many age-related diseases, as well as it seems to reduce the agedependent cognitive decline, preserving learning and memory [9,10,11,12,13,14]
Our results suggested that the four-month moderate running program, even when initiated lately in mice unfamiliar with exercise, was able to trigger multiple adaptive responses within the hippocampal formations of mice undergoing the transition from mature to middle age, a biological period in which we already showed profound biochemical and molecular changes occurring within mouse brain cortices [50]
This protective effect was not achieved through the enhancement of Superoxide dismutase (SOD)- and CATantioxidant defense systems or via an overall increase in reduced GSH equivalents, since we did not observe beneficial effects induced by 4-mo exercise on either the age-dependent reduction in hydrogen peroxide scavenging capacity (Fig. 3c) or the agerelated drop of reduced GSH (Fig. 4)
Summary
Exercise promotes ROS overproduction [7,8], regular and moderate exercise paradigms improve psycho-physical functions, retards aging and lowers the risk of developing many age-related diseases, as well as it seems to reduce the agedependent cognitive decline, preserving learning and memory [9,10,11,12,13,14] This apparent paradox may be explained by taking into account the hormetic responses triggered by habitual exercise through the induction of molecular adaptations, such as the activation of major antioxidant enzymatic systems (e.g., superoxide dismutase, SOD, and catalase, CAT) [15,16,17]. Such an information may be important as interventions aimed at preserving the mitochondrial efficiency (e.g., the caloric restriction) seem to retard signifcantly the overall senescence process in many tissues and organisms [23,24,25]
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