Effects Of Acute And Chronic Stress On Expression Of HIF-1? In Brain Of Mice And Its Relationship With Learning And Memory

Objective and methods:In this study,an acute stress model of animal was established by foot shock and seven stressors were fasting,hathpace,lighting through the night,water deprivation,clod water swimming,oblique cage,foot shock for 2 weeks and 4 weeks respectively,and chronic stress animal models were established.The changes of behavior in mice were detected by tail suspension test and open field test.The spatial learning and memory ability of mice was tseted by Morris water maze.HE staining and immunohistochemistry were used to detect the morphological changes and HIF-1? expression in prefrontal cortex(PFC)and CA1,CA3,DG of hippocampus of mice.The aim of this study was to find out the effects of acute and chronic stress on the behavior and spatial learning and memory ability of mice of different months and the changes of HIF-1? in the brain.Results:1.After 2 and 4 weeks of chronic stress,the weight increase of the mice in the young stress group was slow and the difference was significant compared with the control group.There was no significant difference between the old mice.2.In the tail suspension test,the first immobility time and accumulated immobility time of young stress group mice had no significant difference compared with the control group after 2 weeks of chronic stress;and the first immobility time in young stress group mice was significantly reduced,the accumulated immobility time was significantly prolonged after 4 weeks of chronic stress.The trend in aged mice was samed as young group.After 2 weeks of chronic stress,the first immobility time of aged stress group mice were significantly decreased than the young stress group mice,while the accumulated immobility time had no significant difference.After 4 weeks of chronic stress,the first immobility time in aged stress mice was significantly reduced than the young stress group mice,and the accumulative immobility time also increased significantly.3.In Open field test,the defecation of young stress group mice increased significantly,other indexes had no significant difference compared with the control group after 2 weeks of chronic stress;the rearing and crossing numbers in young stress group mice was significantly reduced,the central residence time increased significantly,and there was no significant difference between other indicators after 4 weeks of chronic stress.In aged stress group,the number of rearing and the crossing decreased significantly,the central grid residence time increased significantly,and there was no significant difference in other indicators after 2 weeks of chronic stress.The trend of the change was consistent with young stress group after 4 weeks.After 2 weeks of chronic stress,the central grid residence time in aged stress group was increased significantly compared with the young stress group,after 4 weeks of chronic stress,the crossing number of aged stress group was decreased significantly compared with the young group,and the central grid residence time was increased significantly.4.In the test of Morris water maze:(1)the escape latency and the total distance: the escape latency and the total distance had no significant difference in young stress group compared with the young control group,the spatial learning ability has no obvious change after 2 weeks of chronic stress;both the escape latency and total distance of young stress group mice were prolonged after 4 weeks of chronic stress;the escape latency and the total distance in aged stress group mice were significantly longer than their control group by chronic stress for 2 weeks and 4 weeks respectively,the spatial learning ability was decreased.After 2 weeks of chronic stress,the escape latency and total distance in four training cycles of aged stress group mice increased significantly compared with the young stress group,while 4 weeks after chronic stress,the trend was consistent with that of 2 weeks after chronic stress and even more obvious.(2)Residence time in target quadrant: the residence time in the target quadrant of young and aged stress group mice were shorter than their control group mice respectively,and there was no significant difference compared with the other 3 quadrants.In the aged stress group,the residence time of target quadrant was shortened but there was no significant difference was found in the 2 and 4 weeks of chronic stress than young stress group.5.HE staining experiment: the neuron morphology in brain of young control group mice was complete after chronic stress for 2 weeks,and it also did not have significantly change in young stress group mice compared to the control group;young stress group mice neurons arranged loosely,atrophy and deformation,uneven staining after 4 weeks of chronic stress;the neuron morphology of aged control group did not change significantly but the number is less;and loosely arranged,aged stress group mice injury more obvious compared with young stress group.6.Immunohistochemical staining experiment: the expression of HIF-1? in DG area of hippocampal increased significantly compared with the control group after 2 weeks of chronic stress;the expression of HIF-1? in each brain area of young stress group was significantly reduced compared with control group after 4 weeks of chronic stress.After 2 weeks of chronic stress,the expression of HIF-1? in hippocampus of aged stress group was significantly lower than that of control group.But after 4 weeks of chronic stress,the expression of HIF-1? both in PFC and hippocampus was significantly lower than that in control group.The expression of HIF-1? in the aged group was significantly lower than that of the corresponding young group.7.In the acute stress experiment,the first immobility time of young stress group mice in tail suspension test was prolonged,and the accumulated immobility time was significantly reduced.In the open field test,the rearing and crossing number and grooming times in young stress group mice increased significantly,the number of defecation decreased significantly.In the Morris water maze test,the escape latency of young stress group mice,compared with the control group,was significantly shortened in each training cycle,and the target quadrant time was increased significantly,compared with the control group.After acute stress,expression of HIF-1? in PFC and CA1,DG area of hippocampal was significantly increased,while the morphology of neuron in prefrontal cortex and hippocampus did not change.Conclusions:1.Chronic stress can cause open field weakening,anxiety and despair behavior in mice,impairs spatial learning and memory ability,the injury is more significant in aged mices;acute stress can cause mice open field behavior significantly improved,enhance spatial learning and memory ability.2.The expression of HIF-1? in all brain regions was significantly decreased with the extension of chronic stress,and the change in aged mice was more obvious.While after acute stress,the expression of HIF-1? increased significantly in hippocampus and forebrain cortex.3.The changes in behavior and learning and memory ability of mice after stress and age related are closely related to the expression of HIF-1? in the brain.