Effect Of Aerobic Exercise On Neural Network Oscillation In Theta And Gamma Frequency Band Of AD Model

Objective: The theta oscillation and gamma oscillation activities of neural networks are closely related to the cognitive function of specific regions of the brain,reflecting the changes of neural network activities at different levels of neuronal groups in the brain.This experiment analyzes the theta activity and theta-gamma PAC intensity in quiet and receiving stimulus situations of 12-month-old 3×Tg-AD mice and then explores the influence of aerobic exercise on the above neural network characteristics of the AD model,to provide experimental basis for non-drug intervention to delay the development of AD diseases.Methods: Adult 3×Tg-AD mice and C57BL/6J mice were used in this study.12-month-old 3×Tg-AD mice and C57BL/6J mice were randomly assigned to AD exercise group(TGE),AD sedentary group(TGS),control exercise group(CE)and control sedentary group(CS).All exercise groups were subjected to treadmill exercise for 12 weeks before the experimental test.The exercise workload consisted of running at the speed of 12msters/min for the first 10 min,5 day/week,60 min/day,15meters/min for the last 50 min,with 0%grade of inclination.Step down avoidance test was used to test the long-term memory ability of mice;Multi-channel recording technique was used to record the activity level of local nerve electrical signals in hippocampal CA1 region and prefrontal lobe region of mice.The characteristic changes of theta oscillation energy were analyzed.The theta-gamma coupling activity in theta oscillation frequency band was detected by Matlab programs.The theta-gamma PAC intensity was evaluated by MVL-MI.The firing types of mice theta band neurons were identified and analyzed,and the firing frequencies of excitatory pyramidal neurons and inhibitory interneurons and the ratio of excitatory to inhibitory were calculated.Results:(1)Behavioral changes: 12-month-old AD mice showed a decrease in latency period and memory in step-down avoidance test,and aerobic exercise significantly improved their behavioral ability(P< 0.01).(2)In awake and quiet state,theta activity in hippocampal CA1 region of AD mice did not change significantly compared with normal control group,while the theta activity in prefrontal cortex was increased(TGS vs CS,P< 0.05);Aerobic exercise can reduce the theta activity(TGE vs TGS,P< 0.05)abnormally enhanced in prefrontal cortex.(3)During tail stimulation test,theta energy in hippocampal CA1 region of TGS group did not change significantly,while theta activities of all four groups was increased in prefrontal lobe compared with quiet state(P< 0.05).(4)In awake and quiet state,theta-gamma coupling in hippocampal CA1 region of AD mice did not change significantly compared with normal control group,and theta-gamma coupling intensity in prefrontal lobe was increased(TGS vs CS,P< 0.05);Aerobic exercise intervention increased theta-gamma coupling in hippocampal CA1 region and decreased theta-gamma coupling intensity in prefrontal lobe(TGE vs TGS,P< 0.05).(5)During tail stimulation test,theta-gamma coupling in hippocampal CA1 region and prefrontal lobe of AD mice was significantly enhanced compared with at rest(P<0.05),while in control group,the signal became lower than resting state(P< 0.05).Aerobic exercise intervention can regulate theta-gamma coupling abnormally enhanced in two brain regions(P< 0.05).(6)In awake and quiet state,PN/IN ratio of hippocampal CA1 region has no change and prefrontal lobe of AD mice was lower than those of normal control group(P< 0.01).Aerobic exercise increased the PN/IN ratio of hippocampal CA1 region and prefrontal lobe region(TGE vs TGS,P< 0.05).(7)During tail stimulation test,compared with the quiet state,the PN/IN ratio in CA1 region of hippocampus in TGS group mice was significantly decreased(P< 0.05),while the PN/IN ratio in CA1 region of CS and TGE group mice was significantly increased(P< 0.05).The PN/IN ratio of prefrontal cortex in the four groups had no significant change.Aerobic exercise improved PN/IN ratio of hippocampal CA1 region and prefrontal lobe in AD mice(P< 0.01).Conclusion:(1)Aerobic exercise can still promote the learning and memory ability of 12-month-old 3×Tg-AD mice;(2)During awake and quiet state,theta activity of the slow frequency band in the prefrontal cortex of the 12-month-old3×Tg-AD mice was increased,theta-gamma coupling intensity of theta frequency band was increased,and pyramidal neurons showed low excitability.Aerobic exercise can improve the excitability of pyramidal neurons and regulates the intensity of theta oscillation and theta-gamma coupling.(3)The slow-frequency theta oscillation,theta-gamma coupling intensity and pyramidal neuron excitability of 12-month-old3×Tg-AD mice hippocampal CA1 in awake and quiet state had no significant difference to the normal control group,while long-term aerobic exercise can adjust the neural network oscillation and improve the response ability to stimulation.