Background: Obesity is associated with cognitive dysfunction and dementia, as well as a reduction in brain-derived neurotrophic factor (BDNF). The calcineurin 1 regulator (RCAN1) regulates neuronal plasticity and depressivefunction by regulating BNDF. Voluntary exercise may improve this condition.
Methods and findings: Voluntary exercise was loaded in apolipoprotein E (ApoE)-/- mice by a high-fat diet (HFE, n=15) over a period of three months. Nonexercising mice with a high-fat diet (HFD, n=15) became overweight. Mice in voluntary exercise group ran on a wheel 5 days/week on the same period, mice without a high-fat diet as a control (NOR, n=15). A Morris water maze, novel object recognition, and forced swimming were evaluated. Chronic exercise significantly reduced body weight and increased the right psoas muscle weight/body weight ratio in the HFE group compared with HFD. Both of BDNF and RCA1 in HFE were expressed to a significantly higher extent in the hippocampus than with HFD. The Morris water maze test, novel object recognition test and forced swimming test were significantly improved in HFE.
Conclusion: Chronic voluntary exercise improved cognitive dysfunction and depressive modes along with increased expressions of BDNF mRNA in the hippocampus and of RCAN1 mRNA in the skeletal muscle.