Acute exercise and brain BACE1 protein content: a time course study

Obesity and insulin resistance are risk factors in the development of neurodegenerative disorders. Previous work suggests that one acute bout of exercise may have beneficial neuro‐protective effects in obese mice. The rate limiting enzyme in the production of amyloid‐beta peptides, BACE1, was reduced in the prefrontal cortex 2 h post‐exercise, however if these effects remain over time is unknown. We aimed to determine how long exercise–induced alterations persist in the prefrontal cortex and hippocampus following a single exercise bout. Male C57BL/6J mice were fed either a low (LFD, 10% kcals from lard) or a high fat diet (HFD, 60% kcals from lard) for 7 weeks. HFD mice then underwent an acute bout of treadmill running (15 m/min, 5% incline, 120 min) followed by 2‐, 8‐, or 24‐h of recovery. The HFD increased body mass (LFD 27.8 ± 1.05 vs. HFD 41.7 ± 0.60 g; P < 0.05) and glucose intolerance (AUC LFD 63.27 ± 4.5 vs. HFD 128.9 ± 4.6; P < 0.05). Prefrontal cortex BACE1 content was reduced 2‐ and 8‐h post‐exercise compared to sedentary HFD mice, however BACE1 protein content at 24 h was not different. Hippocampal BACE1 content was reduced 8‐ and 24‐h post‐exercise. Compared to the LFD, the HFD had higher prefrontal cortex phosphorylation of p38, JNK, and AMPK, indicative of increased neuronal stress. Post–exercise prefrontal cortex p38 and JNK phosphorylation were no different between the HFD or LFD groups, while ERK phosphorylation was significantly reduced by 24 h. The HFD increased JNK phosphorylation in the hippocampus. These results demonstrate the direct and potent effects of exercise on reducing BACE1 prefrontal cortex and hippocampal content. However the reduction in prefrontal cortex BACE1 content is short lived.