| Objective1. To explore the effect of gene, age and gender on behavioral performance and possible pathophysiological mechanisms in Tg-SwDI mice.2. To study the cognitive and non-cognitive behavioral characteristics of the male Tg-SwDI mice using a variety of classical and novel behavioral domains.3. To evaluate the candidate drugs’effect on cerebral amyloid angiopathy or Alzheimer’s disease with Tg-SwDI mouse model and explore the possible mechanisms.Methods1. The behavioral phenotype in different age and different gender groups of Tg-SwDI mice and their corresponding wild-type mice were detected with nesting construction, open field, novel object recognition, Morris water maze and other behavioral paradigms. Mortality, weight and the spontaneous activity of mice in each group were observed. Gene, age and gender impacts on the results as well as the possible pathophysiological mechanisms were analyzed.2. To study male Tg-SwDI mice in order to exclude gender factors, and observe their cognitive and non-cognitive behavioral characteristics through the nesting, open field, novel object recognition, Morris water maze, novel taste neophobia, olfactory test and a series of classic and novel behavioral domains and analyze their possible pathophysiological mechanisms.3. The effects of dl-butylphthalide on Alzheimer’s disease related behavioral and pathological changes were observed in Tg-SwDI mouse model.Results1.(1)Tg-SwDI mice showed age-related decline in nesting qualities and weight.(2)Tg-SwDI mice showed age and gender-related changes in open field exploration activities.(3)Tg-SwDI mice showed cognitive and some non-cognitive function impairment at an early stage(3-4months), which may be related to the early-onset of A P in specific brain areas.(4) The female Tg-SwDI mice display a more serious behavioral abnormalities in some part of the experiment, and occurred epilepsy as well as higher mortality in old age, which may be related to more serious and more frequent brain hemorrhage.2.(1)Male Tg-SwDI transgenic mice showed hypoactivity and weight loss.(2)Male Tg-SwDI mice display symptoms of anxiety and fear associated with memory deficits.(3)Male Tg-SwDI mice were deficient in object recognition, and morris water maze.(5)They did not differ from controls in wire hang, nest-building and forced swimming.3.(1) Long-term treatment with dl-butylphthalide can improve part of the cognitive function in Tg-SwDI mice, but it can’t change their Aa burden;(2) The effective mechanism may be related to its anti-inflammatory effects.ConclusionTg-SwDI transgenic mice showed some abnormal behaviors at an early stage, which seems in accordance with the obvious Aβ deposition at an early age in this transgenic model mice. However some of these anomalies worsened with age, while some made slow progress, it indicated that different behavioral paradigms may represent amerera pathophysiological mechanisms. The same as previous clinical observations and some other related transgenic mouse model of AD, female mice’s pathological process seems to make faster progress than the male’s, suggested that attention should be payed to the gender factor for its influence on the animal model of behavior and the course of the performance. On one hand, the differences will provide good tools to study the role of gender factor on the pathogenesis of AD and CAA process. On the other hand, in some studies, such as drug curative effect evaluation research, the difference should be considered. This system behavioral study of Tg-SwDI transgenic mice found some changes never been reported before, its mechanisms still need to be further studied.This study evaluated of possible curative effect of a cerebral anti-ischemia drug, butylphthalide,which is also an antioxidant drug, in AD/CAA with this mouse model, and found certain cognitive improvement effect. The mechanism may be associated with the anti-inflammatory effects of the drug, suggested it may have application prospect in neurodegenerative diseases. |
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