Aerobic Exercise Regulates Gamma Oscillation in Hippocampal CA1 of APP/PS1/Tau Mice

Abstract

PURPOSE: Changes in gamma oscillations have been observed in multiple brain regions in mouse models of Alzheimer's disease. This study aimed to investigate the effect of aerobic exercise on gamma activity in hippocampal CA1 of APP/PS1/Tau transgenic (3×Tg) mice during awake state when theta oscillation occurs, and the effect on slow gamma activity in CA1 during sleep state when SWRs occur. METHODS: 3×Tg mice (6 months old) and C57BL/6J mice were randomly divided into exercise groups and sedentary groups respectively. The exercise groups were made to run on the treadmill for 1 hour per one day, five times a week, for 12 weeks. The exercise workload consisted of running at a speed of 12 m/min for the first 10 min, 15 m/min for the last 50 min, with 0% grade of inclination. Radial arm maze was used to evaluate the memory function of the mice. Multichannel recording technology was used to record electrical activity of hippocampal CA1 in vivo. Theta oscillation and sharp waves and ripples (SWRs) were detected by MATLAB programs, and spectral analysis was computed using multi-taper methods. Immunofluorescence was used to detect the Aβ deposits in CA1. RESULTS: 12 weeks of treadmill exercise ameliorated working memory (2.00±0.35 vs. 1.20±0.38, p<0.05) and reference memory (5.47±0.36 vs. 3.70±0.45, p<0.05) deterioration of 3×Tg mice. The 9-month-old 3×Tg mice exhibited a reduction of both gamma power (0.33±0.05 vs. 0.51±0.02, p<0.01) during the theta rhythms awaking and slow gamma power (0.50±0.03 vs. 0.55±0.04, p<0.01) during SWRs sleeping in the hippocampal CA1 compared to control mice, respectively. 12 weeks of treadmill exercise could increase gamma power either being awake (0.50±0.06, p<0.01) or being asleep (0.54±0.03, p<0.05) in 3×Tg mice. Furthermore, these disturbances were observed to be consistent with Aβ pathological deposits (AS, 1.42±0.21, p<0.01 vs. CS; AE, 0.53±0.09, p<0.01 vs. AS). CONCLUSIONS: Consistencies between these alteration in gamma power and Aβ deposits suggest that disturbances in rhythmic organization of theta and gamma may contribute to spatial memory deficits in 9-month-old 3×Tg mice. Given these data, aerobic exercise could improve spatial performance by regulating gamma power when theta oscillations or SWR occur. Supported by the National Natural Science Foundation of China (31571229).