| BackgroundAlzheimer's disease (AD), also called Alzheimer disease, senile dementia of the Alzheimer type, primary degenerative dementia of the Alzheimer's type, or simply Alzheimer's, is the most common form of dementia. AD is characterised by loss of neurons and synapses in the cerebral cortex and certain subcortical regions. Both amyloid plaques and neurofibrillary tangles are clearly visible by microscopy in brains of those afflicted by AD. AD is a highly debilitating neurodegenerative disorder characterized by progressive cognitive impairment and memory loss. Its prevalence rate increases with the age, so the harm of AD to human health has become increasingly prominent. AD is less common in aspirin users than non-users, and there are plausible biological mechanisms whereby aspirin might slow the progression of Alzheimer-type pathology.ObjectiveIn this study, the animal model of AD is established by injecting amyloid-beta protein 25-35 into the lateral cerebral ventricle of rats, and treated by continuous feeding with aspirin dissolved in drinking water. The escape latency of the rats is tested in Morris water maze, and the level of IL-6,IL-1β,TNFαin the brain is detected by enzyme linked immunosorbent assay (ELISA) method, while NF-κB and iNOS protein by Western Blot. And the hippocampus CA1 area is observed through optical microscope. And then, we assess the benefits of aspirin in the animal model of AD, and its probable mechanism.MethodsThe experiment techniques in this study include Morris water maze, intragastric gavage, lateral cerebral ventricle injection, ELISA method and Western Blot method.50 rats were equally randomized into 5 groups: (1) High dose aspirin treatment group: the animals were fed with drinking water with 2mg/ml of aspirin dissolved in it for 3 weeks. And then 5μl solution of amyloid-beta protein was injected with a microinjector into the lateral cerebral ventricle. And the animals were fed with drinking water with 2mg/ml of aspirin dissolved in it for another 3 weeks. (2) Middle dose aspirin treatment group: the animals were fed with drinking water with 1mg/ml of aspirin dissolved in it for 3 weeks. And then 5μl solution of amyloid-beta protein was injected with a microinjector into the lateral cerebral ventricle. And the animals were fed with drinking water with 1mg/ml of aspirin dissolved in it for another 3 weeks. (3) Low dose aspirin treatment group: the animals were fed with drinking water with 0.5mg/ml of aspirin dissolved in it for 3 weeks. And then 5μl solution of amyloid-beta protein was injected with a microinjector into the lateral cerebral ventricle. And the animals were fed with drinking water with 0.5mg/ml of aspirin dissolved in it for another 3 weeks. (4) The control group: the animals were fed with drinking water with no aspirin dissolved in it for 3 weeks. And then 5μl solution of amyloid-beta protein was injected with a microinjector into the lateral cerebral ventricle. And the animals were fed with drinking water with no aspirin dissolved in it for another 3 weeks. (5)Sham group: the animals were fed with drinking water with no aspirin dissolved in it for 3 weeks. And then 5μl saline was injected with a microinjector into the lateral cerebral ventricle. And the animals were fed with drinking water with no aspirin dissolved in it for another 3 weeks. At the end of the sixth week, the escape latency of the rats was tested in Morris water maze. And then, the level of IL-6,IL-1β,TNFαin the brain is detected by ELISA method, while NF-κB and iNOS protein by Western Blot. The hippocampus tissue was observed by microscopy.Results1, the mean escape latency of the control group was longer than sham group, respective 42.96±17.51s and 27.21±13.23s. And the mean escape latency of high,middle or low aspirin treatment group was shoter than the control group. 2, biospy showed that aspirin keeped the structure of nerve cells around hippocampus CA1 area normal. 3, injecting of 5μl solution of amyloid-beta protein into the lateral cerebral ventricle, may arise the expression of protein of NF-κB, and could increase the levels of IL-1β, TNFα.. 4, And each group of high,middle or low aspirin treatment group chould deccrease the levels of IL-1β, TNFα.ConclusionThe study demonstrates that Aβ25-35 could cause loss of short-term learning and memory ability, and aspirin could lighten these changes. The effect of aspirin in these changes may be through inhibition of NF-κB activation, which may reduce IL-1β, IL-6, and TNFα's level.
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