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Studies on the Changes of Cdk5 and Synaptic Structural Plasticity of Infra-limbic Cortex of Rats after Conditioned Fear Extinction Training

Author: LiPeiPei
Tutor: LiMin
School: Third Military Medical University
Course: Applied Psychology
Keywords: Fears subside Edge zone of Cyclin -dependent protein kinase 5 Synaptic structure
CLC: B842.3
Type: Master's thesis
Year: 2010
Downloads: 45
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Abstract

In recent years, various disasters occur frequently, an increasing trend in the incidence of post-traumatic stress disorder (post-traumatic stress disorder, PTSD), and is currently not enough in-depth understanding of the pathogenesis of PTSD and its treatment, there are many difficulties PTSD also become a hot research scientists. Clinically, the common method of treatment of PTSD is exposure therapy, traumatic memories subsided, but the fear has faded memory and easy to reproduce, prompted subside memory retention obstacles may and difficult to treat PTSD. Previous studies have shown, is closely related to the occurrence and development of the functional status of the prefrontal cortex (prefrontal cortex, PFC) with PTSD. Under the edge of the rodent PFC cortex (infralimbic cortex, IL) is a regression of memory retention of important parts, however, about the molecular mechanisms of the area subsided memory is not fully understood. Many studies have shown that the cyclin-dependent kinase 5 (cyclin-dependent kinase 5, Cdk5) and its activator P35 widespread, Cdk5/P35 complexes can change the functional and structural plasticity in hippocampal synapses in the cerebral cortex and affect conditioned fear memory formation and regression of memory acquisition. However, in the conditioned fear subsided after training, the rats the IL District, Cdk5 and P35 protein expression, and kinase activity what changes? Process IL District of synaptic structure what changes will happen? These have not been reported. To this end, we designed two experiments. Experiment a conditioned fear subsided training the limbic area Cdk5 expression and activity changes to: investigate the training in conditioned fear subsided, of Cdk5 expression of rat IL area and activity changes. Methods: SD rats were randomly divided into subsided group, the regression of the control group and normal control group. Sound combined with plantar electric shock to the establishment of a model of conditioned fear, subsided group after 24h fear establish subside training regression of the control group does not subside training, both groups at different time points (fear establish 2,4 and 8 days) after the behavioral tests, the use of the immunohistochemistry assay rats in each group IL area Cdk5 immune reaction positive cells, Western blot detection Cdk5 and its activator P35, P25 protein expression levels, and liquid scintillation detection Cdk5 activity changes. Results: (1) subsided group and regression of the control group Jiang Li time percentage in fear after the establishment of the first 2 days and 4 days were significantly lower than the normal group (86.03 ± 8.90, P lt; 0.01); established to fear first 8 days, subsided group basically returned to normal, and the regression of the control group (36.18 ± 12.60) is still lower than the normal group (P lt; 0.01). The comparison of the different time points in the same group: progress over time, the level of fear of the two experimental groups showed a gradual downward trend (P lt; 0.01). (2) The results of immunohistochemistry: fear after the establishment of the first two days, subsided rats IL area Cdk5 immune response was no difference in the number of positive cells with the normal group subsided positive cells of the control group (429 ± 70) in the normal group (322 ± 52, P = 0.026) and subsided group (358 ± 63, P lt; 0.05); in fear after the establishment of the first four days, the the subsided group significantly reduced the number of positive cells (208 ± 30, P lt; 0.01), subsided control group returned to normal; fear after the establishment of the first eight days, subsided group also returned to normal and no significant difference between the control group and subsided. (3) the results of the Western blot was: subsided after training 1 week, subsided rats IL area Cdk5 protein expression was reduced trend: subsided after 1 and 3 days, the expression of the normal group was no significant difference to subside after seven days (1.35 ± 0.13) less than the normal group (1.89 ± 0.06, P lt; 0.05); established in fear subsided control group Cdk5 protein 4 days increased (2.94 ± 0.19), significantly than subside group (1.78 ± 0.20, P lt; 0.01) and normal group (P lt; 0.01); eight days to fear establish basically back to normal, but significantly more than subsided group (P lt; 0.01). The two groups of P35 expression with the normal group, no significant difference; two groups of P25 protein expression were significantly higher than in the normal group. Subsided after training for one week, group P25 subsided the expression gradually reduce: subsided after 7 days (1.60 ± 0.12) was significantly lower than subsided after the first day (2.14 ± 0.24, P = 0.032) and day 3 (2.17 ± 0.21 , P = 0.026); subsided control group in this process, there is an increasing trend: the fear after the establishment of the expression of two days (1.78 ± 0.16) was significantly less than four days after the fear establish (2.50 ± 0.19, P = 0.039) and 8 days (2.58 ± 0.40, P = 0.027). (4) The results of the liquid scintillation method: subsided rats the IL District, of Cdk5 the activity subsided after training and three days was significantly increased (the product radioactivity values ??were 3107.78 ± 536.42 and 3330.05 ± 597.82, P lt; 0.01), but subsided after 7 days (2179.89 ± 327.20) basically returned to normal levels (1812.08 ± 175.21); while subsided three days, the control group was significantly higher than the normal group (P lt; 0.05 or P lt; 0.01 ). Two experimental groups, two days after the establishment of the fear was no significant difference, the kinase activity subsided group fear establish and 8 days significantly lower than subsided control group (P lt; 0.05 or P lt; 0.01 ). Conclusion: IL area conditioned fear Cdk5 protein expression and activity increased, rats Jiang Li behavior more; After after subside training, of Cdk5 protein expression decreased gradually, faster return to normal activity, the fear response in rats is gradually reduced, these changes may be beneficial for memory retention subsided. Second experiment, the conditioned fear subsided training rats under the edge of synaptic number density and changes of synaptic interface structure Objective: To investigate the conditioned fear subsided after training, changes in a rat IL synaptic density and synaptic interface structure . Methods: SD rats were randomly divided into subsided group, the regression of the control group and normal control group. Sound combined with plantar electric shock to establish a model of conditioned fear subside in fear establish 24h subside training, to subsided control group does not subside training, 8 and 22 days of the two groups were established at different time points (fear) Jiang Li behavior of rats was measured, and then quickly decapitated, the IL area transmission electron microscope specimens produced by conventional methods, and observed by transmission electron microscopy, video, analysis of the number of district synaptic density and synaptic interface structure parameters, including: synaptic interface curvature , changes in the thickness of the active region length, the width of the synaptic cleft and postsynaptic dense material (postsynaptic density, PSD). Results: (1) behavior: subsided rats keep score two points in time with the normal group (91.17 ± 3.07), no significant differences; subsided control group not in fear after the establishment of the first 22 days (66.73 ± 8.75) Jiang Li for longer than eight days (38.40 ± 10.12, P = 0.021), but had significantly less than the normal group (P lt; 0.01) and regression group (P lt; 0.05 or P lt; 0.01). (2) synaptic number density: at both time points, the regression of the number of synapses in rats IL density (per unit volume, the number of synapses) were significantly higher than the control group (0.36 ± 0.06, P lt; 0.05) ; established in fear subsided control group on day 8 the number of synaptic density (0.39 ± 0.04) and normal no difference, but after the establishment in the fear of the first 22 days (0.22 ± 0.03) was significantly lower than the normal group (P = 0.038) and the subsided group (0.48 ± 0.06, P lt; 0.01). (3) the synaptic interface parameters: among the three groups show no significant difference in the synaptic interface curvature and the synaptic cleft, and the length of the active region and the thickness of PSD significant difference. Compared with the normal group, seven days subsided after training, the the subsided rats IL area PSD thickness no significant changes to subside after the first 21 days, the the PSD thickness increased (53.87 ± 11.39, P = 0.017); subsided control group at two time points showed thinning of the thickness of the PSD (P lt; 0.05 or P LT; 0.01), and the synaptic active region are less than the length of the dissipated group (P LT; 0.05 or P LT; 0.01). Conclusion: The establishment of conditioned fear the IL District, the number of synaptic density decrease in synaptic structure damage, but subsided training, the increase in the number of synaptic density in the district, enhance the efficiency of synaptic transmission, favor conditioned fear response reduction. In short, can speculate from these two experiments: the conditioned fear subside training change with IL IL District Cdk5 District synaptic structural plasticity changes there are some links, conditioned fear established rat IL Cdk5 activity and P25 expression continues to rise, persistence may reduce synaptic density to change synaptic structure and synaptic function in the area decline, the fear response in rats; however, subsided training gradually decreased P25 expression, Cdk5 activity rapid return to normal, there may be conducive to the structural plasticity of synapses, and behavioral performance in rats Jiang Li percentage of time that can be quickly returned to normal levels.

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