Physical exercise improves memory and cognition in physiological aging and Alzheimer’s disease (AD), but the mechanisms remain poorly understood. Here, we test the hypothesis that Aβ oligomer accumulation, neuroinflammation, and glial cell activation may lead to disruption of synaptic transmission in the prefrontal cortex of 3 × Tg-AD Mice, resulting in impairment of learning and memory. On the other hand, treadmill exercise could prevent the pathogenesis and exert neuroprotective effects. Here, we used immunohistochemistry, western blotting, enzyme-linked immunosorbent assay, and slice electrophysiology to analyze the levels of GSK3β, Aβ oligomers (Aβ dimers and trimers), pro-inflammatory cytokines (IL-1β, IL-6, and TNFα), the phosphorylation of CRMP2 at Thr514, and synaptic currents in pyramidal neurons in the prefrontal cortex. We show that 12-week treadmill exercise beginning in three-month-old mice led to the inhibition of GSK3β kinase activity, decreases in the levels of Aβ oligomers, pro-inflammatory cytokines (IL-1β, IL-6, and TNFα), and the phosphorylation of CRMP2 at Thr514, reduction of microglial and astrocyte activation, and improvement of excitatory and inhibitory synaptic transmission of pyramidal neurons in the prefrontal cortex of 3 × Tg-AD Mice. Thus, treadmill exercise reduces neuroinflammation, glial cell activation and improves synaptic transmission in the prefrontal cortex in 3 × Tg-AD mice, possibly related to the inhibition of GSK3β kinase activity.

Objective: Anxiety and depression-like symptoms occur in the early stages of Alzheimer’s disease. Hippocampal Sirtuin 1 (SIRT1) signaling mediates anxiety- and depression-like behavior. Exercise training improves anxiety and depression-like behavior in various disease models, such as the rat chronic restraint stress model, rat model of posttraumatic stress disorder, and rat model of fetal alcohol spectrum disorders. Here, we aimed to investigate whether exercise ameliorates anxiety- and depression like behaviors in APP/PS1 mice and explore the potential mechanisms.Methods: After eight weeks of exercise intervention, we assessed anxiety- and depression-like behaviors in Alzheimer’s disease (AD) model mice. We then measured the levels of SIRT1, peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC1α), nuclear respiratory factor 1 (NRF1), mitochondrial transcription factor A (TFAM), and mitochondrial biogenesis (CO2, ATP6, and mitochondrial content) using immunofluorescence, reverse transcription-quantitative real-time PCR, and transmission electron microscopy. Finally, we investigated the effects of pharmacological activation of SIRT1 on anxiety- and depression-like behaviors, the SIRT1/PGC-1α/NRF1/TFAM signaling axis, and mitochondrial biogenesis.Results: We first observed that treadmill exercise improved anxiety- and depression-like behaviors in six-month-old APP/PS1 mice and increased SIRT1 levels in the hippocampus. Pharmacological activation of hippocampal SIRT1 function also reduced anxiety and depression-like behaviors in APP/PS1 mice. Meanwhile, both treadmill exercise and pharmacological activation of hippocampal SIRT1 increased the levels of PGC1α, NRF1, TFAM, and enhanced mitochondrial biogenesis (CO2, ATP6, or mitochondrial content) in the hippocampus of APP/PS1 mice.Conclusion: These findings reveal that treadmill exercise reduces anxiety- and depression-like behaviors in six-month-old APP/PS1 mice by enhancing the SIRT1-dependent PGC-1α/NRF1/TFAM axis, promoting mitochondrial biogenesis in the hippocampus.

Overweight and obesity are showing an increasing prevalence among college students. But gender differences related to overweight and obesity in Chinese college students have not been adequately characterized. This cross-sectional study aimed to investigate the gender differences in overweight and obesity among college students, then, investigate why these gender differ-ences exist. A total of 622 undergraduate students (females: N = 245, male: N = 377), aged 18–23 years, were recruited from the Hebei Sport University in China. Anthropometric data, physical activity and sedentary behaviors, eating behaviors (cognitive restraint, uncontrolled eating, and emotional eating) and food addiction were collected through anthropometric measurements and questionnaires that included the International Physical Activity Questionnaire short-form (IPAQ-SF), the Modified Food Addiction Scale version 2.0 (mYFAS 2.0), and the Three Factor Eating Questionnaire (TFEQ). Here, we show that female college students had a significantly higher prevalence of overweight and obesity (Female: BFP ≥ 25%; Male: BFP ≥ 20%) than male students. Meanwhile, Female college students had a higher mean body fat percentage (BFP) and a lower waist circumference, waist-to-hip ratio, visceral fat area, fat-free mass, muscle mass, and skeletal muscle mass compared to male college students. Additionally, female college students were more likely to be moderate physical activity than males, while male college students were more likely to be severe physical activity. Female college students had significantly higher mean scores for cognitive restraint, uncontrolled eating, and emotional eating than males. Our findings indicated that the higher prevalence of overweight and obesity rates in female college students than male students may be due to de differences in physical activity and eating behavior.