| Alzheimer's disease is the most common cause of dementia in elderly people. It refers to a primary degenerative neurological disease, which onset at the old age or pre-old age people. It is a continuous high-level neurological function disorder that includes memory, thinking, analytically, visual & space recognition, emotional impairment, but absence of the state of consciousness. Research advances have enabled detailed understanding of the molecular pathogenesis of the hallmarks of the disease—i.e., plaques, composed of amyloidβ(Aβ), and tangles, composed of hyper-phosphorylated tau. The number of Aβplaques in the brain and is closely related to the degree of dementia. So far, treatment of the cognitive impairment caused by AD are mainly restricted to improve symptoms and slow disease progression, there is no effective drug can significantly improve cognitive function and reverse the disease process.The Aβdeposition AD rat model created by infusion Aβinto hippocampus of rat imitated the pathological changes of AD to a certain extent, that is associated with neuronal Aβdeposition and cognitive dysfunction mainly refers to memory impairment. The model has made a great contribution to the research of pathogenesis of AD, as well as to treatment methods and drugs for AD. Polyene phosphatidyl choline (PPC) is a commonly drug used in clinical liver disease's adjuvant therapy. It is a phosphatidyl choline that the triglycerides skeleton of the lecithin containing unsaturated fatty acid named docosahexaenoic acid (DHA) and arachidonic acid (AA). There has been results show that DHA has a protective effect on Aβtoxicity and phosphorylation of tau; AA has a protective effect on mobility of membrane in aging hippocampal neurons, and help to increase the plasticity of synapses.Based on the backgrounds indicated above, in this study, we prepared rat models of AD, apply Polyene phosphatidyl choline to treatment, observed by water maze to test the effects of Polyene phosphatidyl choline on AD rat model's cognitive changes of behavior; by morphology and immunohistochemical staining to observe the effects of Polyene phosphatidyl choline on morphological changes of Aβlevels, glial cell activation and the impact of changes in synaptic structure in brain of AD model rats. Further evaluate the therapeutic effects and possible therapeutic mechanism. So as to provide a theoretical basis for the method of treat AD with Polyene phosphatidyl choline.The main results are as follows:1. Behavioral changes in Morris water maze test:①location navigation test (memory training test): the time of the rats to find hidden underwater platform from four quadrants was used to evaluate. The memory acquisition capability of Aβinfusion model rats was improved by PPC treatment②. Spatial probe test (memory retention test): to analysis swim time and length in the target quadrant ones was placed the platform to evaluate the space exploration capabilities of rats in every group. PPC treatment can improve their memory retention capacity after injury by Aβinfusion.2. The morphology of the hippocampus Nissl staining: Compared with normal control group and sham control group,the Aβmodel group show obvious increasing amount of Nissl body in target area of needle penetration and infusion;the neuronal death and loss were especially obvious in the CA1 region of hippocampus. Compared with Aβmodel group,the PPC treatment group indicate significant decreasing of the number of Nissl body in the same area,and amount of neuronal death and loss were markedly reduced.3. Aβimmunohistochemistry staining of hippocampal infusion area: compared with normal control group and sham control group,the Aβmodel group show obvious increasing amount ofβ-amyloid deposits close to the area of needle penetration and infusion;the neuronal death and loss were especially obvious in the same area. Compared with Aβmodel group,the PPC treatment group indicate significant decreasing of the number ofβ-amyloid deposits in the same area,and amount of neuronal death and loss were remarkably reduced.4. Changes of glial cell activation: in the hippocampus CA1 area after injection of Aβ1-40, showing that the regional proliferation of astrocytes was activated, showing GFAP-positive astrocytes cells significantly increased, larger cell bodies, neuritis growing thicken and longer; the activation of astrocytes reduced after PPC treatment. Around the Infusion area show the proliferation of activated microglia. Showed by immune fluorescence, the Iba1-positive microglia cells significantly increased, as dense granular. PPC treatment reduced the activation of microglia around the infusion area.5. synapse ultrastructure changes in transmission electron microscope: microstructure in the hippocampal CA1 area of normal rats was clear to see, synaptic structure was normal, the presynaptic membrane, postsynaptic membrane, synaptic cleft and synaptic vesicles visible; after infusion of Aβ1-40, CA1 zone microstructure was fuzzy, normal synaptic was damaged, breakdown and disappearance of synaptic vesicle; after given PPC, the chaos of the microstructure in CA1 area return to normal, we can see clearly the presynaptic membrane, postsynaptic membrane, synaptic cleft and synaptic vesicles.Overall, our study confirmed the Polyene phosphatidyl choline to some extent reduce the AD model rats infusion ofβ-amyloid protein on behavior and morphology. Our study is the first time to introduce PPC—a clinical drugs treat liver disease into the treatment area of AD research. Although the mechanism of to follow what the specific PPC can be used to treat AD model rats is still unclear, but viewing from the results,PPC is indeed a certain drug can treat and attenuate AD. Through what channels PPC reduces and reverses the behavior and the pathological changes of AD will be a subject with significant value. About the research in the future we will further from neurological behavior,β-amyloid pathway, neuronal loss, neural immune, mechanisms of neurogenesis and other aspects. Expect to provide further theoretical and experimental basis for the clinical treatment of AD. |
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