Shnyo Pn, Shnshn Guo, Jiru Di, Ynrong Gu, Guoxing Wng,Yulong Wng, Zhenghong Qin, Li Luo,*

    a School of Physical Education and Sports Science, Soochow University, Suzhou 215021, China

    b School of Life Sciences, Fudan University, Shanghai 200032, China

    c Department of Rehabilitation, Shenzhen Second People's Hospital, The First Affiliated Hospital, Shenzhen University School of Medicine, Shenzhen 518035, China

    d Department of Pharmacology and Laboratory of Aging and Nervous Diseases, Jiangsu Key Laboratory of Translational Research and Therapy for

    Neuro-Psycho-Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China

    Keywords:

    Exercise

    Trehalose

    Cognitive function

    Autophagy

    A B S T R A C T

    Exercise is recognized as an effective strategy to delay brain aging, which is related to the activation of autophagy. Trehalose is a natural compound that can activate autophagy and exert beneficial effects in delaying brain aging. In this study, we investigated whether trehalose may exert neuroprotection similar to those of exercise in delaying age-related cognitive decline. Fifteen-month-old male C57BL/6 mice underwent swim exercise and/or were treated with 2% trehalose for 12 weeks. Trehalose, exercise and the combination of exercise and trehalose intervention improved the learning and memory of aged mice. They also improved the ratio of LC3-II/LC3-I, the protein level of LC3-II, Bnip3L, and Parkin respectively. Additionally, both exercise and trehalose increased the phosphorylation of AMPK. Exercise decreased cortical phosphorylation of mTOR and S6k, whereas trehalose did not change these cortical levels. These data indicated that exercise and trehalose might modulate autophagy through mTOR-dependent or mTOR-independent pathways,respectively. However, a combination of exercise and trehalose did not play a synergistic role in improving cognitive function and modulation of autophagy. Taken together, our findings suggest that trehalose exerts similar effects to those of exercise in delaying age-related cognitive decline and that it may thus represent an exercise mimetic to delay brain aging. ......