| As long with the aging of population, the occurrences of neurodegenerative diseases in elderly, such as Alzheimer’s disease, Parkinson’s disease and huntington’s disorder, are increasing. And these diseases severely threaten the health of the aged, furthermore more middle aged people are also in danger.Alzheimer’s disease (AD), with the highest incidence and most population of infirmities of age, is charactered by serious memory damage, progressive cognitive disorders, dystrophy and mood change. Studis showed that the most distinct pathologic feature of AD patients is the amyloid deposition and neurofibrillary tangles in brain. Until now on, the mechanism of AD is still unknown, but many hypothesizes have been suggested, including:the Amyloid Cascade Hypothesis, the Lysosomal Dysfunction Hypothesis, Oxidative stress Hypothesis and so on.After so many researches had proceeded about AD, people find that the inflammatory reaction also occur in the brain of AD patients, then it becomes a hot point that if the serious inflammatory reaction can lead the occurrence of AD. Neuroglia especially the microglia plays an important role in inflammatory reaction. Under the state of pathology, such as neurodegenerative diseases, stroke, mechanical damage, and infiltration of tumor, the microglia will be activated. It will migrate to the cell which are dead or damaged, then the cells debris will be cleared, the function of microglia seems like macrophages in periphery immune system. Besides this, after activating, pre inflammatory reaction regulatory factors will be released, such as cytokine, ROS, complement factor, Secretory neurotoxin and NO. They weaken the neurons’function and finally lead neurons dead.In this study, LPS was injected into peritoneal cavity, which will cause the chronic inflammation all over the body, then the body weight, ability of cognition of ethology, the state of microglia in hippocampus CA1 and cerebral cortex of brain and the cytokine IL-6 was detected separately in productive phase and recovery phase, and then explore the effects of peripheral chronic inflammation on mice’s cognitive ability and function of neuroglial cells.Analysis of result: 1. The measurement of the body weight of mouse indicate that comparing to the control group, the mouse which were injected LPS into peritoneal cavity lose their weight significantly (P<0.05); After the recovery phase, there was no significant different between the two groups.2. Ethology detection indicates that, in inflammatory reaction phase, assay of Morris water maze of the LPS-10 and LPS-10-2 groups is significant longer than control group (P<0.05), and LPS-5 has no significant different with control group. In recovery phase, LPS-10-2 is significant different with control in each detective point (P<0.05).3. Immunohistochemistry detection of microglia and astrocytes indicates that, at hippocampus CA1, comparing to the control group, the number of microglia in treated group increased significantly (P<0.01), the activated astrocytes in LPS-10 group and LPS-10-2 group increased significantly (P<0.05); In recovery phase, comparing to the control group, the number of microglia in LPS-10-2 increased significantly (P<0.05), number of astrocytes has no significant different. At cerebral cortex of brain, comparing to the control group, the number of microglia in treated group increased significantly (P<0.01), number of astrocytes has no significant different; In recovery phase, microglia and astrocytes in treated groups has no significant different with the control group.4. The result of Realtime-PCR and Western-blot indicates that, at hippocampus CA1, comparing to the control group, the level of IL-6, IL-1βmRNA and protein in treated groups increased significantly (P<0.05), and the expression of GDNF decreased significantly (P<0.05); In recovery phase, comparing to the control group, expression of IL-6 and IL-1βin LPS-10 group and LPS-10-2 group increased significantly (P<0.05), level GDNF increased significantly (P<0.05). At cerebral cortex of brain, comparing to the control group, the level of IL-6, IL-1βin treated groups increased significantly (P<0.05), level GDNF decreased significantly (P<0.05); In recovery phase, level of IL-6 in LPS-10 group and LPS-10-2 group increased significantly (P<0.05), level GDNF in treated groups increased significantly (P<0.01).Conclusion:1. In this study, model of inflammation all over the body was constructed by injecting LPS into peritoneal cavity, this inflammation will influence the brain, and will activate the microglia and lead the releasing of relevant cytokine.2. Inflammation all over the body with different degree will change the ability of learning and cognitive ability of mouse, and the ability of cognition will damaged by high concentration, long time and continuous inflammation. Even if the inflammation is removed, the disability of cognition cannot recover in short time.3. Level of nutritional factor of nerve cells-GDNF increased significantly in recovery phase, indicates that it may take part in the recover of neurons, but the detail mechanism is still unknown. |
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