Aerobic Exercise Differential Alters Intrinsic Neuronal Properties In The 3xtg Mouse Model Of Alzheimer's Disease

Abstract

PURPOSE: Alterations in network activities in Alzheimer’s disease (AD) are accompanied by an early imbalance of excitation and inhibition that related to cognitive function. Although that aerobic exercise could enhance synaptic plasticity from various AD mouse models have been found, the properties of neurons firing in specific conditions remain poorly understood. This study was to investigate the neurophysiological signals underlying the effects of aerobic exercise on the brains of APP/PS1/Tau transgenic (3χTg) mice and 129 mice as wild type (Wt) control at 9 months of age. METHODS: 3χTg mice (6 months old) were randomly divided into exercise groups and sedentary groups (AS, AE), and Wt mice as cohort control. The exercise groups would run on the treadmill for 12 weeks. Multichannel recording technology was used to record population spikes in cortical and hippocampal region at 9 months of age in vivo during awake or sleep state. Spike sorting was performed using offline sorter software. Pyramidal cells (PNs) were distinguished from putative interneurons (INs) on the basis of average firing rate, bursting properties, and spike width. RESULTS: Recordings took place across 5-7 consecutive days while mice were awake exploring or asleep, and the number of spikes was calculated every 10 sec as a session. During awake, in three AS, AE and Wt mice, we recorded 15 PNs, 48 PNs and 10 PNs, while 9, 23 and 11 INs in cortex (with a total of 192 place fields); 36 PNs, 77 PNs and 35 PNs, while 10, 37 and 15 INs in hippocampus (with a total of 330 place fields). During sleep state, with a total of 138 place fields, we recorded 22 PNs, 19 PNs and 13 PNs, while 7, 15 and 14 INs in cortex; 29 PNs, 58 PNs and 21 PNs, while 9, 24 and 11 INs in hippocampus (with a total of 270 place fields). In both awake and sleep state, IN firing rates were differential changed in AS compared to the control, and the ratio of IN/PN was lower in both cortex (0.6±0.02, 0.31±0.00) and hippocampus (0.28±0.00, 0.31±0.01) of AS compared to Wt mice (1.1±0.02, 0.43±0.01/ 1.08±0.02, 0.52±0.01, P<0.01). Exercise attenuated the phenomena (0.48±0.01, 0.48±0.01/0.79±0.02, 0.41±0.02, p<0.01). CONCLUSIONS: Aerobic exercise could regulate aberrant cellular neurophysiology related to cognitive impairments dependent network function.