| BackgroundDepression is one of the most common mental disorders among the population.White matter,of which myelin sheath is an important component,is the main connecting structure responsible for signal conduction between different brain regions.Studies have shown that white matter is one of the main structures showing pathological changes of depression,and white matter in prefrontal cortex,hippocampus and other brain regions of depression model of rats will be damaged.Repetitive transcranial magnetic stimulation(rTMS)is an effective physical therapy method,which has been used in the clinical treatment of depression at present,but its mechanism is not completely clear.Some studies have shown that its mechanism may be related to promoting the functional recovery and regeneration of myelin sheath and oligodendrocytes.ObjectiveTo observe the effect of rTMS intervention on the improvement of depression-like behavior of depression model rats induced by solitary rearing combined with chronic unpredictable mild stress(CUMS),and the effect of rTMS intervention on the expression of myelin basic protein(MBP)and oligodendrocyte marker 2 ’3-cyclic nucleotide phosphodiesterase(CNP)in the prefrontal cortex and hippocampus of rats,and to explore the possible mechanism of rTMS in improving depression.Methods1.Fifty adult male rats of SPF grade were selected and evaluated by baseline behavior named sugar water preference test.Rats with large difference in sugar water preference index were excluded.Among the remaining rats,8 rats were randomly sampled as normal control group,and the remaining 40 rats were model group.The normal control group was fed in IVC environment,and the model group rats were fed combined with CUMS in solitary cage.Three weeks later,the successful depression model rats were evaluated and selected by behavioral test,and they were randomly divided into depression group,sham stimulation group and rTMS group according to the principle of random sampling.2.rTMS Intervention: Rats in rTMS group were given rTMS intervention for 3 weeks.The specific setting parameters of rTMS are: frequency 10 Hz,duration 10 minutes,a total of 500 pulses,and the rats received an interval of 2 days after 5 days of intervention.The total course of rTMS intervention was 3 weeks.Rats in sham stimulation group were only given the same rTMS intervention environment,but their heads were far away from magnetic stimulator coil while not receiving any stimulation.3.Behavioral Evaluation Method: Sugar water preference test was carried out on rats to evaluate the degree of loss of pleasure in rats.Open field test was used to observe the inquiry behavior and tension degree of rats in new environments.The depression state of model rats was evaluated through the above behavioral test data.4.Western blotting(WB)and qPCR were used to detect the protein and mRNA expression levels of MBP and CNP in prefrontal lobe and hippocampus of rats.5.SPSS 20.0 software was used to statistically analyze the experimental results of each group.The statistical analysis method of one-way ANOVA was used to express the measurement data with mean ± standard deviation((?) ± s).The test result P <0.05 can be considered to have statistical difference.Use software named Graph Pad Prime to draw diagrams.Results1.Behavioral Evaluation: Before the model was prepared,the behavioral performance of rats in each group was uniform,and there was no significant difference;After receiving CUMS for 3 weeks,the sugar water preference index(t=4.143,P=0.00026),the total distance of activity in the open field(t=6.574,P=0.00077)and the central residence time in open field for 10min(t=5.803,P=0.00002)of the model group were significantly lower than those of the normal control group.After rTMS intervention,the sugar water preference index(F=13.130,P=0.00015),the total distance of open field activity(F=12.232,P=0.00027)and the central residence time of open field(F=49.266,P=0.00000)of all the groups of rats were significantly different.Compared with the normal control group,the sucrose water preference index,the total distance of activity of the open field in the model group and the sham stimulation group were lower than those in the normal control group,and the differences were statistically significant(P <0.01),while the retention time in the center area of the open field in the depression group and the sham stimulation group was significantly longer than that in the normal group(P <0.05).Compared with the rTMS group,the sucrose water preference index,the total distance of activity of the open field in the model group and the sham stimulation group were lower than those in the rTMS group,and the difference were statistically significant(P <0.05),while the residence time in the center area of the open field in the depression group and the sham stimulation group was significantly longer than that in the rTMS group(P <0.05).2.Results of Protein Expression Test: After 3 weeks of rTMS intervention in the rTMS group,the protein expression levels of MBP and CNP in the prefrontal lobe and hippocampus of all the groups of rats were significantly different.Among them,the protein expression levels of MBP and CNP in the prefrontal lobe and hippocampus of rats in the depression group and the sham stimulation group were significantly lower than those in the normal control group(P ＜0.05).The protein expression levels of MBP and CNP in the prefrontal lobe and hippocampus of rats in the rTMS group were significantly increased than the depression group and the sham group(P ＜0.05).3.Results of Gene Expression Test: Compared with the normal control group,the expression levels of prefrontal lobe and hippocampal myelin related indexes(MBP)and oligodendrocyte marker(CNP)genes decreased in the depression group and the sham stimulation group(P ＜0.05)while those of the rTMS group increased significantly(P ＜0.05).Conclusion1.The protein and mRNA expression level of MBP and CNP in prefrontal cortex and hippocampus of depression model rats decreased,which may be related to the pathogenesis of depression.2.High-frequency rTMS intervention may improve depression-like behavior in rats by promoting the expression of MBP and CNP in prefrontal cortex and hippocampus of rats,which may be one of the mechanisms of rTMS improving depression. |
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