Chronic Stress On The Influence Of Learning And Memory In Mice And Functional Studies In Glial Cells

Living in community, people always encounter various external stimulations, which influence people’s mood and cause different forms of pressure. The pressure is able to change people’s mood, then impact the function of cerebral cortex, and finally lead to dysfunction of the organism. Previous research showed that the stress in life is a critical element to result in various diseases. Whereas, extreme chronic stress could activate continuously physiological responses which are harmful to the organism, especially disturb the function of hippocampus. As the pivotal region regulating the stress, Hippocampus and cortex has always been the focus of the study of stress response.The glial cells, main immune cells in nervous system, play an important role in preventing brain diseases. In normal Situation, glial cells will be activated temporarily by the stress stimulus to make the central nervous system keep steady-state.However, the glial cells perform different biological functions with different stimuli. For example, after brain injury, the activated glial cells play a key role in immune regulation, tissue repair and cell repair in nervous system.Recent research indicated that long-term chronic stress poisons the hippocampus and causes the hippocampal cells atrophy and apoptosis, which correspondingly damages spatial learning and memory of rodents and humans. Finally it may be evolved into Neurodegenerative disease. However, the extent and scope of the glial cells activated by chronic stress is unknown.Our studies thus explore whether chronic stress affects the learning and cognitive ability, and further track the activation and function of the glial cells. In this research, we hope to provide new therapeutic target for Neurodegenerative disease caused by pressure.In this research, we are aimed to explore Behavioral changes, morphological changes and biological function of gliacytes after chronic stress in 3-months-old Kunming mice. Also, we design experiments to observe the functional reactivation of these mice which were raised normally with the same time span following the chronic stress. After imposing continuously 40-days different pressure treatment and immediately 40-days normal breeding on the mice, we detected the ability of spatial learning and memory of the mice and the recuperation of this ability. Subsequently, we observed the activated state of glial cells, monitored the change of mRNAs of related secreted cytokines (BDNF,GDNF,IGF-1, IL-1β,iNOs), and detected the change of GDNF,IL-1βprotein. The result shows that the ability of spatial learning and memory of the mice went to decay obviously after impressed chronic stress. However, after 40-days normal breeding, this ability was recovered to normal level or may be higher comparing with the level of before pressure. The chronic stress activated gitter cells and astrocytes from hippocampus and preforntal cortex, normal breeding made the two types of cells in hippocampus and gitter cells in preforntal cortex return to previous level. However, the astrocytes in preforntal cortex continually remained actived state. Correspondingly, in the period of chronic stress, the level of mRNA and protein of protective factor GDNF was increased. Inversely, the mRNA and protein level of inflammatory factor IL-1βwas reduced, in the period of normal breeding, in hippocampus, the GDNF mRNA and protein remained increased and IL-1βmRNA and protein remained degressive. In preforntal cortex, GDNF mRNA and protein was slightly fallen, whereas IL-1βmRNA and protein was interestingly improved.The result above revealed that chronic stress activated neurogliocyte in hippocampus and preforntal cortex and caused corresponding physiological change, which may play an important role in protecting neuron. After normal breeding following closely the pressure, the change caused by chronic stress could return to normal levels in the cells of hippocampus. Meanwhile, the protective factor may increase continually to result in enhanced protection. Interestingly, the astrocytes in preforntal cortex continually remained actived state. We hypothesized this kind of activation may associate with Neurodegenerative disease. But it needs further study whether constant activation of the astrocytes in preforntal cortex is a bridge between chronic stress and neurodegenerative disease.