| BackgroundLithium carbonate is a mood stabilizer,a synergist for the treatment of bipolar disorder,depression treatment and antipsychotic drugs,but the mechanism of action is not yet clear.White matter damage is considered to be the pathological manifestation of white matter damage in many mental diseases such as schizophrenia,depression and bipolar disorder.White matter damage may disrupt signal transmission between neurons,leading to cognitive or neurological dysfunction.Cypridyl oxalate(Cuprizone,CPZ)can induce demyelinating white matter damage in animal models,and gamma oscillations are neurons and The rapid oscillating activity of the neuron group reflects the neuronal functional status.ObjectiveTo evaluate the behavioral changes of mice with white matter injury,to understand the gamma oscillation characteristics of hippocampal CA3 region at different times and the changes under lithium carbonate intervention in mice with white matter injury,and to explore the repairing effect of lithium carbonate on injured white matter.Method1.Research Design and Animal Grouping: 100 C57BL/6 mice were selected and randomly divided into 2 groups(n=50),a model group(CPZ group)and a control group(CON group).The CON group fed the normal food and the CPZ(0.2% biscyclohexanone oxalyl dioxime)group fed CPZ for 6 weeks.At the end of 6 th week,10 mice were randomly selected from the above groups to be sacrificed to prepare a brain slice,and thecorresponding ? oscillation characteristics were recorded.2.Model preparation and behavioral tests: The CPZ model was fed with feed containing 0.2% CPZ per day for 6 weeks;after 6 weeks in CON+Li and CPZ+Li groups,lithium carbonate was given at 2 g/kg,while in CON and CPZ groups,normal food was given.The behavioral changes in mice were assessed by the "sucrose water preference test","open field test","Y-maze test",and "rotary rod test".3.Brain slice preparation and gamma oscillation recording: After anesthesia was performed with 10% chloral hydrate,cardiac perfusion was performed with a 0°C slicing solution until mice limbs became white.Mice brain tissue was rapidly removed,fixed,horizontally cut to slices of thickness of 300 mm.The tablets were covered with glass and incubated for 60 min.Kainate(KA)was used to induce a stable gamma frequency oscillation.Spike2 was used to record the gamma frequency oscillation spectrum by extracellular microelectrode.4.Statistical methods: Spike2 software is first used to analyze the power and main frequency data of ?-network oscillations off-line and to extract data;statistical analysis of behavioral data,power and frequency data of ?-network oscillations and their correlation are performed using SPSS 21.0 software package.Result1.Behavioural changesThe average daily intake of CPZ was lower than that of CPZ 6 weeks before(P=0.009).After fed with lithium carbonate,the diet of mice increased(P=0.010)and the weight of mice increased(P=0.007).The open field test showed that the difference of total distance and distance from the center of the 4 groups were statistically significant.There were significant differences between total distance and distance from the center(F8=19.745,P8=0.000)(F10=19.658,P10=0.000);the total consumption of sucrose water and the percentage of sucrose water preference in the sucrose water experiment were statistically significant at the end of 10 th week,and the statistical values were(F=13.747,P=0.000),(F=11.475,P=0.000).In the rotary rod experiment,four groups of total distance and distance from the center of falling time differences at the end of 6th,8th,10 th week were statistically significant,and the statistical values were(F=37.974,P=0.000),(F=16.847,P=0.000),(F=5.752,P=0.003).In the discovery of new and old arms of maze experiment,the difference between the 6th weekend,8th weekend,and the 10 th weekend were statistically significant,the statistical values were(F=39.240,P=0.000),(F=16.047,P=0.000),(F=29.152,P=0.000).2.Detection of power and peak frequency in CA3 region of hippocampus by gamma-neural network oscillationThe power value of ? oscillation in CPZ group after CPZ model was significantly lower than that in CON group(t=5.325,P=0.000).There was a significant difference in the power value of ?-oscillation between the two weeks after the intervention of lithium carbonate at the 8th weekend(F=11.001,P=0.000).At the end of the 10 th week after4-week lithium carbination,there was a significant difference in power between four groups(F=10.649,P=0.000).The main frequency analysis results of gamma oscillations showed no significant difference between the two groups after CPZ modeling at the end of the 6th week;there was no significant difference between the four groups at the end of the8 th and 10 th weekends.3.Analysis of Correlation between ? Oscillation and BehaviorAfter lithium carbonate intervention for 2 weeks,there was a significant positive correlation between the ? oscillation power and the total distance of open field test,the consumption of surcose water,the falling time of the rotary rod experiment,the percentage of spontaneous alternation reaction,the total number of arms of spontaneous alternation reaction,and the ratio of the new and old arms of the Y-maze experiment.The Pearson correlation coefficients were r=0.326,r=0.321,r=0.498 and r=0.444,r=0.526,r=0.470(P<0.05).After lithium carbonate intervention for 4 weeks,there was a significant positive correlation between the?oscillation power and the total distance of open field test,theconsumption of surcose water,the falling time of the rotary rod experiment,the percentage of spontaneous alternation reaction,the total number of arms of spontaneous alternation reaction,and the ratio of the new and old arms of the Y-maze experiment.The Pearson correlation coefficients were r=0.482,r=0.414,r=0.599,r=0.571,r= 0.558(P<0.05).There was a significant negative correlation between ?oscillation power and the percentage of sucrose water consumption.The Pearson correlation coefficient was r=-0.329(P=0.038).ConclusionIn mice with white matter damage,gamma oscillations are impaired,energy is reduced,and synchronicity is reduced.Lithium carbonate can promote ? oscillation repair.Accompanied by the repair of this process,the behavior is improved.Lithium carbonate may exert its antipsychotic effects by repairing damaged myelin sheath structures. |
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