The Asymmetric Effects Of Chronic Stress On The Hippocampal Function And Structure

Objective: To establish the chronic multiple stress rat model, systematically explore chronicstress asymmetricly impact on hippocampus (function and structure) from function (mainly arebehaviors), structure and expression of functional protein, and to further explore its possiblemechanism.Methods: Male Sprague-Dawley rats, screened indistinguishably into control group (n=12) andchronic stress group (n=12), Using5weeks chronic unpredictable mild stress (CUMS) methodsto establish the rat model of chronic stress. Observing the body weight of the two group ratsduring experiment process and using the Open-field test to observe the anxiety level, activityability of rats, then evaluate the model whether to establish successfully. Using Morris watermaze and Y maze examine the hippocampal spatial cognitive function, investigate chronic stressimpact on the capability of acquire, retain and retrieval spatial clue. After the behavior tests,further study chronic stress impact on bilateral hippocampus, mainly are the changes ofmorphology and number of neuron, and using Immunohistochemical analysis to detect theautophagic level of neuron. And the changes of functional protein Gap-43in bilateralhippocampus was observed by Western blotting analysis.Results:1. Effects of chronic stress on spatial cognitive function: weight growth of model groupis restrained, in open-field test compared with the control group, the model group of thehorizontal move distance, the number of rearing and through the inner zone were significantlyreduced, indicating that the chronic multiple stress rat model establish successfully. In Morriswater maze test, compared with the control group, the model group latency delayed in reversallearning stage, and stayed time in purpose quadrant significantly reduced, average distance topurpose location significantly increase. In Y maze experiment, compared with the control group,the model group stayed time in novel arm and the number of pass the novel arm significantlyreduced.2. The impact of chronic stress on the hippocampal structure: in control group, thehippocampal CA1pyramidal cells were clear and complete, the distribution were tight and order,while model rats hippocampal CA1area pyramidal cells layer is thinner, dendritic atrophy, cellgap widened, the cell body shrink, arrangement sparse, cell number reduce. The hippocampalCA3pyramidal cells of control group arranged in order, the cytoplasm stained deep, while inmodel group, hippocampal CA3pyramidal cells, arrangement were sparsely scattered, cell gap widened, cell loss, cytoplasmic staining were light. The control group of rats hippocampalgranule cells in DG area clear and complete, the distribution of area were large and dense, whilethe model group of rat hippocampal DG area granular cell except some slightly modifiedexternal, most of all have no difference compared with the control group. Compared with controlgroup, the number of neurons of model group, hippocampal CA3reduced, and the number ofright hippocampi was significantly less than the left. And the number of CA1area neurons ofmodel group significantly decreased, both the left and right hippocampus CA1area comparedwith control group. However, compared with control group, the number of granule cells indentate gyrus had no significant change.3. Effects of chronic stress on the expression of Gap-43in hippocampus: compared with thecontrol group, the Gap-43protein up-regulated expression in right hippocampi of model grouprats while the Gap-43protein expression level in left hippocampi has no significantly change.And the protein expression level of right hippocampi significantly higher than the left.Conclusion:1. Impairment of chronic stress on rat spatial learning and memory cognize function, relatedto the change of morphology and number of neuron cells in hippocampus.2. Chronic stress induced morphology and number of neuron cells in hippocampus CA3asymmetric change, indicate chronic stress may cause right hippocampus Specific–damage.3.Chronic stress induced model group hippocampus CA1and CA3areas neurons autophagyactivate, indicate the change of morphology and number of neuron cells in hippocampus CA1and CA3subregion related to autophagy, however did not present asymmetric phenomenon.4. Gap-43protein involved in the process chronic stress impaired model grouphippocampus CA1and CA3subregion neurons, and present asymmetric phenomenon.