Chronic Stress On Spatial Learning And Memory Function In Mice And Expression Of BDNF In The Brain

With the growing competition in the world,people usually live in a circumstance with different kinds of chronic stressors.Unpredictable and uncontrollable stressful events exert powerful influences on the physiology of every organ system of the body via their impact on both the physiological and cognitive processes of the central nervous system.Many studies showed that chronic stress was harmful to health,even led to diseases,meanwhile it impacted the brain cognitive functions and leads to learning-memory impairment.Brain-derived neurotrophic factor(BDNF) is a member of the neurotrophin family.Besides its actions on neuronal survival, growth and prevention of neurodegeneration,it can enhance the connection of synapse and influence the neural plasticity and synthesis of neurotransmitters and neurotrophins,also relate with learning and memory.This study aims to investigate the effects of chronic stress on the ability of spatial learning-memory in different group mice and the role of BDNF in its mechanism in hippocampus and frontal cortex,so as to provide a new measure and idea for clinical pharmacology.In the present study,we examined the effects of chronic stress on learning-memory impairment and the expression of BDNF in hippocampus and frontal cortex of different group mice(2 month old and 15 month old).The chronic stress model in 15 days with multiple stressors(footshock,crowding and crowding+thermal stimulus,unexpectedly given to mice) was applied.The locomotion of mice was tested in open field area.The ability of spatial learning -memory of mice was measured using Morris water maze.The morphologic changes in hippocampus and frontal cortex of brain were observed by HE dye,and the expressional changes of BDNF in mice were detected by immunohistochemical method.The results of this study are as follows:1.Compared with the control group mice,except for defecation,all parameters of the young and aged stress mice such as weight,square crossing,rearing and grooming were decreased.The aged control group mice exhibited less grooming than the young control group.The aged stress group mice had more remarkable changes in square crossing and grooming than the young control group.And these parameters were still on 7days after stress.2.In water maze test,the young and aged stress group mice showed lower performance in reaching the platform in acquisition test,and they spent less time in the target quadrant in probe trials as compared with the control group mice,and 7days after stress,the impairment was still on.The aged control and stress group mice had poorer performance than the young control and stress group after stress and 7days after stress,respectively. 3.The stress group mice displayed obviously morphologic changes such as intercellular space broaden,cell imperfection,the Neis body was shallow to dye even fuse in hippocampus and frontal cortex after stress and 7days after stress.Compared with the young stress group,the aged stress group showed more cell imperfection after stress and 7days after stress.4.Immunohistochemical analysis results showed the number and sectional area of BDNF positive neurons in hippocampus and frontal cortex were significantly reduced in the stress group mice after stress,and the changes were still on 7days after stress,compared with the control group mice.The aged control and stress group mice showed lower BDNF expression in hippocampus and frontal cortex than the young control and stress mice after stress and 7days after stress.Conclusion:1.Chronic stress could induce different extent damage in weight and behavior of the young and aged group mice,the aged group mice had more serious abnormal of behavior under chronic stress.It indicates that aging is one of the important influence factors in chronic stress.2.Chronic stress could increase the escape latency and decrease the swimming time in the target quadrant in different group mice,and the aged group mice had poorer performance than the young group mice after stress and 7days after stress.It indicates that chronic stress cause the impairment of different group mice's spatial learning-memory ability,and the aged animals have more significant impairment of spatial learning-memory ability.3.Chronic stress could cause the morphology changes such as intercellular space broaden, cell imperfection,the Neis body was shallow to dye even fuse in hippocampus and frontal cortex. The aged group mice showed more seriously cell imperfection than the young group mice after stress and 7days after stress.4.Chronic stress could induce significant reduction of BDNF expression in hippocampus and frontal cortex.The aged group mice had much lower BDNF expression than the young group mice after stress and 7days after stress.In this study we found that the changes of BDNF expression in hippocampus and frontal cortex were positively correlated with the impairment of mice's spatial learning-memory ability after stress and 7days after stress.It suggested spatial learning-memory ability was persistently impaired by chronic stress,not only during stress periods but also during recovery periods and BDNF played an important role.