ABSTRACT
Objective:To explore the effects of sulforaphane (SFN), an activator of Nrf2, on anxiety and fear memory in Alzheimer's disease(AD) model mice and mechanism.Methods:The AD mice and wild type (WT) mice with the same background were randomly divided into four groups ( n=12 for each group): wild type + normal saline group (WT+ NS), wild type + sulforaphane (WT+ SFN), AD model + normal saline group (AD+ NS) and AD model + sulforaphane group (AD+ SFN). SFN was dissolved in normal saline (0.9% NaCl) and prepared solution with concentration of 1 g/L.According to body weight, mice in WT+ SFN group and AD+ SFN group were intraperitoneally injected with SFN (10 mg/kg), and mice in WT+ NS group and AD+ NS group were intraperitoneally injected with the same volume of normal saline once a day for 30 days.The open field test was used to detect the autonomous exploration ability and anxious behavior of mice.The elevated cross maze was used to detect the anxiety of mice.Conditional fear test was used to test the fear memory behavior of mice.Finally, the expression of superoxide dismutase(SOD) and malondialdehyde(MDA) in the hippocampus and cerebral cortex were detected by ELISA.Two-way ANOVA analysis was performed using GraphPad Prism 8.0.2 software. Results:In the open field test, the percentage of time in central region in AD+ SFN group ((9.99+ 0.37)%) was higher than that of AD+ NS group ((8.47+ 0.42)%) ( q=3.842, P<0.05). In the elevated cross maze, the percentage of time in open arm of AD+ SFN group ((26.2±1.6)%) was higher than that in AD+ NS group ((15.8±1.0)%) ( q=7.452, P<0.01). In the conditional fear test, all the mice of the four groups developed the fear memory, but AD+ SFN group showed higher freezing time ratio ((64.5±3.8)%) than AD+ NS group ((51.0±4.3)%)( q=5.266, P<0.01) in the testing stage.After SFN intervention, the important indicator of oxidative stress, the expression levels of SOD in hippocampus ( q=6.370, P<0.01) and cortex ( q=7.858, P<0.01) of AD mice increased, while the level of MDA in hippocampus ( q=5.146, P<0.05) and cortex ( q=5.833, P<0.01) decreased. Conclusion:SFN may inhibit oxidative stress through Nrf2 pathway, thereby improving anxiety and fear memory in AD mice.
ABSTRACT
Objective:To explore the relationship between the Spike and the Gamma rhythm of the local field potential (LFP) in Alzheimer's disease (AD) transgenic mice during fear memory activity.Methods:Six-month-old APP/PS1/tau three transgenic (3xTg) mice and wild-type (WT) mice were divided into 3xTg group and WT group, with 10 mice in each group. The electrodes were embedded into the hippocampus of mice under sterile conditions, and the behavioral experiment of conditioned fear box test was carried out two weeks later. The changes of Gamma rhythm, Spike and Burst firing were recorded and analyzed by the wireless telemetry device which embedded in the mouse head. Finally, the correlation between Gamma rhythm and Spike was calculated by entropy value.Results:(1) In behavioral experiments, the freezing ratio caused by conditioned stimulation (CS) in 3xTg mice was ((54.07±2.32)%), which was significantly lower than that of WT mice ((76.21±2.88)%) ( t=4.796, P<0.01). (2) Simultaneously recorded the average power of the Gamma oscillation in the Pre-CS period of the WT mice was ((11.574±1.147) dB), which increased to ((18.108±1.177) dB) after CS ( t=3.386, P<0.01). After CS administration, the average power of Gamma in 3xTg group((12.346±1.345) dB) was significantly lower than that of WT group ( t=3.423, P<0.01). (3) The frequency of Spike release in WT mice during the Pre-CS period was ((5.667±1.475)times/s), significantly increased to ((11.008±1.335) times/s) after CS ( t=3.542, P<0.01). The frequency of Spike release of 3xTg mice after CS ((5.249±1.033) times/s) was significantly lower than that of WT group ( t=4.788, P<0.01). (4) The Burst duration of WT group in pre-CS and CS period were ((0.550±0.043)s) and ((1.075±0.034)s), respectively. It suggested that the Burst firing frequency of WT group increased significantly after conditional stimulation ( t=5.188, P<0.01). However, the release interval of 3xTg group after CS ((0.619±0.033)s) was significantly lower than that of WT group ( t=3.352, P<0.01). (5) After CS, the Spike-Gamma entropy curve of WT mice was always higher than that of 3xTg mice. The maximum correlation of WT group and 3xTG group were (0.403±0.031) and (0.314±0.028), respectively. The Spike-Gamma correlation of the 3xTg group was significantly lower than WT mice ( t=3.372, P<0.01). Conclusion:The defect of fear memory in Alzheimer's disease may be caused by the disharmony of Spike-LFP (Gamma) distribution.