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The therapeutic effect of vaccination on neuronal change in animal models with Alzheimer disease

疫苗接种对阿尔茨海默病动物模型神经元变化的治疗作用

基本信息

批准号：
12670960
负责人：
TADOKORO Mamoru
金额：
$ 1.98万
依托单位：
St. Marianna University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670960/
关键词：
Alzheimer disease amvloid plague amyloid-β-peptide model mouse

项目摘要

It has recently been reported that amyloid injection (vaccine) into PDAPD mice resulted in marked decrease of amyloid plaque deposition (APD), although it is uncertain whether or not amyloid plaque is the real cause of Alzheimer disease. Amyloid- β -peptide injection into animal models of Niemann-Pick disease type C (NPC) mice (spm, NIH) and Down syndrome (Dn) mice was projected in that whether or not such vaccination effects the brain tissue with APD and neurofibril change, APD itself is responsible for Alzheimer's etiology, and vaccine is an effective therapy. The pathological difference is only slight between NPC-spm and NPC-NIH mice, but the life span is shorter in NIH mice. We then vaccinated spm mice every 2 weeks. The clinical manifestation and life span were not different from non-vaccined mice. Neurologically, glial reaction of astrocytea was slightly affected in vaccinated mice. To evaluate the long span effect, Dn mice were vaccinated up to 10 months (8 month vaccination). Neural atrophy in cerebral cortex and hippocampus was progressive from 4 -month-old mouse to 10 -month-old mouse. Ten- month-old mouse showed calcification in pallidum and gliosis in basal forebrain. However, gliosis in cerebral subcortex of white matter, stained with GFAP was milder.

最近有报道，淀粉样蛋白注射（疫苗）到PDAPD小鼠中导致淀粉样蛋白斑块沉积（APD）显著减少，尽管淀粉样蛋白斑块是否是阿尔茨海默病的真实的原因还不确定。将β-淀粉样肽注射到C型尼曼-皮克病（NPC）小鼠（spm，NIH）和唐氏综合征（Down syndrome，Dn）小鼠动物模型中，无论这种疫苗是否影响脑组织APD和神经原纤维的变化，APD本身是阿尔茨海默病的病因，疫苗是一种有效的治疗方法。NPC-spm和NPC-NIH小鼠的病理学差异很小，但NIH小鼠的寿命较短。然后我们每两周给spm小鼠接种一次疫苗。临床表现和寿命与未接种小鼠无差异。神经学上，接种疫苗的小鼠星形胶质细胞的神经胶质反应受到轻微影响。为了评估长跨度效应，将Dn小鼠接种长达10个月（8个月接种）。从4月龄到10月龄，小鼠大脑皮层和海马的神经萎缩是进行性的。10月龄小鼠苍白球钙化，基底前脑胶质增生。脑皮质下呈白色的胶质细胞增生较轻。