Study On The Mechanism Of Aerobic Exercise On The Expression Of NCAM In The Frontal Lobe And Learning And Memory Of Depression Model Rats

Objective: Chronic unpredictable mild stress(CUMS)is pushing SD rats towards depression.To explore the mechanism of the influence of aerobic exercise on the expression of neural cell adhesion molecule(NCAM)and spatial learning and memory in depression model rats.Methods: 48 male SPF SD rats aged 3 months,310 10 g,were randomly divided into 4 groups after 1 week of adaptive feeding: natural control group(C),depression model group(D),model exercise group(ME)and post-depression exercise group(DE).Each group of 12(n=12).Group C was fed naturally for 8 weeks.In group D,depression was modeled for 4 weeks and then fed naturally for 4 weeks.The ME group received aerobic exercise intervention during the 4-week depression modeling process,and then fed naturally for 4 weeks.The DE group received 4 weeks of aerobic exercise intervention after 4 weeks of depression modeling.CUMS was used for 4 consecutive weeks.After modeling,body weight,open field,sugar water test and ELISA were used to determine the content of DA to evaluate the success of rat modeling.Morris water maze experiment was used to determine the effect of aerobic exercise intervention in different periods on spatial learning and memory of depression model rats.At the end of 8 weeks,the whole brain was severed and the frontal lobes were separated.HE staining and immunofluorescence were used to observe the structural changes of frontal lobe.Real-time PCR and western-bolting were used to detect the expression of NCAM mRNA and protein in frontal lobe,respectively.Results: 1.Modeling results:(1)body weight results: there was no significant difference in the measured body weight of the rats.After the modeling started,the body weight of the rats in each group was different on day 7,and the body weight of group D and DE was significantly lower than that of group C(P < 0.05).The ME group was significantly lower than the C group(P < 0.01).From the 14 th day to the end of modeling,group D,ME and DE were significantly lower than group C(P < 0.01).(2)open-field experiment results: the activity,average velocity,central region time,central region distance and total distance in group D were significantly lower than those in group C(P < 0.05).The indexes of open-field experiments in the ME group and the DE group were significantly higher than those in the D group(P < 0.05)(3)results of sugar water consumption experiment: there was no difference in the total consumption of rats in each group(P > 0.05).White water consumption of group D and DE was significantly higher than that of group C(P < 0.01).There were significant differences in white water consumption and sugar water consumption between ME group and DE group(P < 0.05).The consumption of sugar water in group D and DE was significantly lower than that in group C(P < 0.05).The sugar water consumption ratio of group D and DE was significantly lower than that of group C(P < 0.01),and there was a significant difference between the two groups(P < 0.01).(4)brain DA content test results: DA content in the whole brain of rats in group D was significantly lower than that in group C,ME group and DE group(P < 0.01).There was no significant difference in DA content between ME group and DE group(P > 0.05).2.Test results of spatial learning and memory ability:(1)the results of the positioning and navigation experiment showed that there was no significant difference in the time spent in the escape latency period of the first 2 days between the groups(P > 0.05).After the third day,rats in each group gradually showed different degrees of differences and the time of escape latency was shortened and gradually stabilized.On the third day of the positioning navigation experiment,the time of group D was significantly longer than that of group C,ME and DE(P < 0.01).Although there was a difference on the 4th and 5th days,the difference tended to be stable.On the 6th day of the positioning navigation experiment,the duration of escape latency in group D was significantly longer than that in group C,ME and DE(P<0.05).In the process of location-navigation experiment,there was no significant difference between ME group and DE group in the duration of escape latency(P > 0.05).(2)space exploration experiment on day 7: the number of times of group D passing through the platform was significantly lower than that of group C,ME group and DE group(P < 0.01).There was no significant difference in The Times of crossing the platform between the ME group and the DE group(P > 0.05).3.HE staining results of the frontal lobe of the rats in each group showed that the number of neurons in the frontal lobe of the rats in group C was the highest,and the neurons were arranged in order.The number of neurons in the frontal lobe of group D decreased and the arrangement was disordered.The number of frontal lobe neurons in the ME group and the DE group was significantly higher than that in the D group.Molecular biology:(1)mRNA expression of NCAM gene in group D was significantly lower than that in group C by real-time PCR(P < 0.01).MRNA expression levels of NCAM genes in ME group and DE group were significantly higher than those in D group(P < 0.01).(2)expression levels of NCAM protein in the frontal lobe detected by Western Blotting: the expression levels of histones in group D and ME were significantly lower than those in group C(P < 0.05).The histone expression levels in ME group and DE group were significantly higher than those in D group(P < 0.01).(3)immuno-fluorescence staining results of NCAM protein expression in the frontal lobe: there was clearly positive expression of NCAM in the cytoplasm of neurons around the granular layer of the frontal lobe.5.The frontal NCAM protein expression and NCAM mRNA and behavior and the correlation of the results of learning and memory: kuang regional time reduced,sugar water consumption in the centre and through the original less than to the frontal NCAM protein and frontal NCAM mRNA decreased,improve the frontal NCAM protein by aerobic exercise and the frontal NCAM mRNA expression,thus improving by CUMS stimulus to depression behavior and the ability of learning and memory.The expression of NCAM protein and NCAM mRNA in frontal lobe were positively correlated with behavior,learning and memory.Conclusion: 1.CUMS stimulation resulted in significant decreases in body weight,open field experiment related indexes(activity,average speed,central region time,central region distance and total distance),sugar water consumption ratio and whole brain DA content,which proved that the depression model was successfully constructed in rats.2.CUMS stimulation induced depression in rats,and decreased expression of NCAM in the frontal lobe of rats,resulting in decreased learning and memory ability.3.Aerobic exercise intervention can up-regulate the expression of NCAM in the frontal lobe and effectively improve the learning and memory ability of depressed rats.Therefore,NCAM is one of the neurobiological mechanisms to improve the learning and memory of depressed rats.