Short-term resistant exercise ameliorates cognitive dysfunction in 9-month 3xTg Mice

Abstract

Objectives:It has long known the beneficial effects of physical exercises on brain health. However, most of the studies focus on aerobic exercise. Little is known about resistance exercise (RE) in the brain. We hypothesis that a short-term period of resistant training can improve cognitive functions and related pathological changes. Methods:3xTg mice mice at 9-month-old were trained using a ladder-climbing protocol for 5 weeks with 3-4 training sessions per week. For each session, mice were forced to climb up a 1-meter ladder with progressively heavier weight attached to tail for 15 times with 2 minutes rest during each trail. Effects of RE on cognition and muscle strength were examined by Y-maze and weight lifting test, respectively. Brain and muscle were collected for WB, RT-PCR and immunohistochemistry. Results:Resistance training for 5 weeks reduced body weight, better cognition by Y-maze test. However, increased muscle strength and hypertrophy occurred only in wild type mice but not 3xTg mice. There was significant increase in mRNA levels for IL-1β, IL-6, IL-10, TNF-α and FGF21 in muscle; but not in the brain. pJNK was reduced by RE in the frontal cortex but not the hippocampus. pan-Tau was decreased in the frontal cortex, while ptau-AT180 was decreased in the frontal cortex/hippocampus after RE. Synaptobrevin and synaptotagmin were increased in the frontal cortex or in the frontal cortex/hippocampus, respectively. Conclusion:Taken together, RE training prevented weight gain and preserved cognitive function in 3xTg mice. Furthermore, RE modulated neuroinflammation, tau phosphorylation and synaptic proteins.