Effects Of Aerobic Exercise Training On Nerve Oscillation Frequency Bands In Prefrontal Cortex Of Alzheimer Disease Mouse Model

Objective: This study aims to observe the oscillation characteristics of prefrontal cortex local neural network in different frequency bands of delta,theta,alpha,beta and gamma in the pre-clinical(4-month old)AD model,and the effects of 8-week regular aerobic exercise on the characteristics of each frequency band,to explore the possible mechanism of aerobic exercise in delaying the occurrence and development of AD,and to provide certain laboratory basis for non-pharmaceutical personalized lifestyle intervention in high-risk population of AD.Methods: 1)Grouping: 30 healthy APP/PS1/Tau transgenic mice(4-month-old)were evenly and randomly divided into AD sedentary control group(AS)and AD aerobic exercise training group(AE).15 healthy C57BL/6J mice(4-month-old)served as sedentary control group(CS).All groups were provided with standard chow and tap water ad libitum.2)Training protocol: AE group started aerobic exercise training from the age of 2 months.The exercise training was forced treadmill running for 8 weeks,5 d/w,60 min/d.The running started at 12 m/min for 10 minutes,and then the speed was increased to 15 m/min for 50 minutes.3)In vivo observations:multichannel technology was used to implant microarray electrodes in the prefrontal cortex of the mice.After one week surgery recovery,neuroelectric signals of the mice were collected at three different occasions: resting in cage(Rest phase),standing on the immobile rotarod(Preparing phase)and accelerated rotarod(Performance phase).The collected signals were analyzed for time-frequency,and for power spectrum density analysis of neural oscillation frequency bands.Offline sorter recognized neuron spikes,and Neuroexplorer classified neurons on basis of autocorrelation and cross-correlation features.In the end,the numbers of activated pyramidal neurons(PN)and interneurons(IN)in different periods were counts,and then the ratio of IN/PN firing frequency was calculated to evaluate the balance of excitation and inhibition in each period.Results:(1)Neural oscillation PSD at Rest phase: For the AS group,PSD was significantly increased in delta,theta,alpha and beta bands(P<0.01),but decreased in gamma band(P<0.01),compared with the CS group.For the AE group,PSD in delta,theta,alpha and beta bands were significantly decreased(P<0.01),but gamma band was significantly increased compared with AS(P<0.01).(2)Neural oscillation PSD at preparing phase: for all of the three groups,the PSD of all bands was significantly lower at the preparing phase of low speed(5rpm)compared with Rest phase(P<0.01).For the CS group,PSD bands of delta,theta and alpha were significantly higher at the preparing phases of 15 rpm and 20 rpm than at the preparing phases of low speeds(5rpm and 8rpm;P<0.01);Nevertheless,there was no significant difference in PSD gamma at the preparing phase of any rotation speed.In AS group,PSD of delta,theta,alpha,beta and gamma was significantly increased at the preparing phase of each individual rotation speed compared with the preparing phase of the corresponding preceding lower speed(P<0.01).In AE group,PSD bands became significantly higher at the preparing phases of 15 rpm for delta band(P<0.01),20 rpm for alpha band(P<0.01),and 8rpm for beta band(P<0.01),compared with the preparing phage of the respective preceding lower speed;however,there was no significant difference in PSD theta and gamma bands between the preparing phages of any rotation speeds.(3)Neural oscillation PSD during accelerated rotarod movements: for the CS group,PSD delta and theta bands were significantly higher at8 rpm than at any lower speeds(lower than 8rpm: P<0.01),alpha band was significantly higher at 15 rpm than at any lower speeds(lower than 15 rpm P<0.01),and beta and gamma bands were significantly higher at 8rpm than at 5rpm,15 rpm,and 20rpm(P<0.01).For the AS group,comparison with CS group,PSD delta,theta,alpha and beta bands showed an increasing trend during the first 5rpm period(P<0.01),and PSD gamma band was higher at 8rpm than at lower speeds(lower than8rpm;P<0.01).For the AE group,PSD delta,theta,alpha bands were higher at 15 rpm than lower speeds(lower than 15rpm;P<0.01),and changes in beta and gamma bands were the same as those in the CS group(P<0.01).(4)Neuron classification: totally 92 neurons were identified from the three groups,of which 62 neurons were PN and 30 were IN.In the CS group,27 neurons were identified,of which 17.8 ± 4.1 were PN,and 10.8 ± 2.2 were IN,and in the AS group,out of a total number of 34 identified neurons,24.5±2.1 were PN,and 9.0±2.8 were IN.The AE group had 31 identified neurons,of which 21.5±2.1 were PN and 9.5±0.7 were IN.During accelerated rotarod movement,a total number of 112 neurons were identified from the three groups,including 77 PNs and 35 INs.In the CS group,33 neurons were identified,including19.5±3.5 PNs and 10.5±0.7 INs.In the AS group,40 neurons were identified,including 30.0±0.7 PNs and 11.0±1.4 INs.In the AE group,39 neurons were identified,including 27.0±0.9 PNs and 12±1.41 INs.(5)IN/PN ratio: IN/PN ratio is3.76 for the CS group,5.18 for the AS group,and 4.25 for the AE group.No significant difference was observed in IN/PN ratio between any of the three groups,and between Rest and the moment right before any speed of rotarod movement.During accelerated rotarod movements,the AS group presented significantly higher IN/PN ratios from 8rpm to 15 rpm and 20 rpm than the CS group at the corresponding speeds(8rpm: P<0.01;15rpm and 20rpm: P<0.05).In contrast,at the same speeds(8rpm,15 rpm and 20rpm),the AE group presented significantly lower(P<0.05)IN/PN ratio than the AS group.Following the increase in speed,AS group presented an increased trend in IN/PN ratio.There was no significant difference in IN/PN ratio between the CS group and the AE group at any rotational speed.Conclusions:(1)At rest,the power of low-frequency oscillations in the prefrontal cortex of preclinical(4-month-old)APP/PS1/Tau transgenic mice was increased.At preparing phase and performance phase,the power of low-frequency oscillations in delta,theta,alpha and beta and gamma was changed,but not in significance.(2)Aerobic exercise can effectively regulate the power of low-frequency oscillations in delta,theta,alpha,and beta,and gamma,and improve the state of cortex.