Development of murine models for aging brain, Senescence-Accelerated Mouse (SAM)

开发大脑老化小鼠模型——衰老加速小鼠（SAM）

基本信息

批准号：
02507002
负责人：
TAKEDA Toshio
金额：
$ 22.59万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Developmental Scientific Research (A)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1992
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02507002/
关键词：
Senescence-Accelerated Mouse (SAM)Animal model Senescence Deficits in learning & memory Brain atrophy 脳萎縮

项目摘要

1. Neuroaxonal dystrophic changes were observed in the nuclei fasciculi dorsalis of medulla oblongata in SAM-P/8 mice. The changes appeared earlier and progressed more rapidly in SAM-P/8 than did in SAM-R/U. beta/A4 protein-like immunoreactivity was observed in the form of granular structures(beta-LIGS) in various regions,including the medial septum, cerebral cortex, hippocampu and so on. beta-LIGS increased in number with aging, predominantly in SAM-P/8 with deficits in learning and memory.2. The vacuolization in SAM-P/8 was marked in magnocellular reticula formation (MGRF). The severity of deficits in learning and memory closely correlated with the total area and number of vacuoles in MGRF of brain stem. Furthermore, MGRF lesioned SAM-R/1 mice showed a severe deterioration in passive avoidance tasks and an impairment in the acquisition stage of active avoidance performance. These results strongly suggest that a pathogenic role of the spongiform degeneration in brain stem in deficits in learning and memory in SAM-P/8.3. An inbred SAM-P/10 strain has been established as a model of agerelated brain atrophy. Morphometrical studies showed that frontal cortex including prefrontal cortex, other neocortical regions, posterior piriform cortex, entorhinal cortex anterior olfactory nucleus, amygdala, and caudate putamen were atrophy-prone regions Shrinkage of the neuronal somata and loss of large neurons with age are unique for SAM-P/10, both of which bring about age-relate atrophy in cerebral cortex in SAM-P/10.

1. SAM-P/8小鼠延髓背束核观察到神经轴突营养不良的改变。与 SAM-R/U 相比，SAM-P/8 中的变化出现得更早，进展也更快。在内隔、大脑皮层、海马等多个区域均观察到以颗粒结构（β-LIGS）形式存在的β/A4蛋白样免疫反应性。 beta-LIGS数量随年龄增长而增加，主要存在于学习记忆缺陷的SAM-P/8中。2． SAM-P/8 中的空泡化在大细胞网状结构 (MGRF) 中被标记。学习记忆缺陷的严重程度与脑干MGRF中空泡的总面积和数量密切相关。此外，MGRF 损伤的 SAM-R/1 小鼠在被动回避任务中表现出严重恶化，并且在主动回避表现的获得阶段受到损害。这些结果强烈表明，脑干海绵状变性在 SAM-P/8.3 学习和记忆缺陷中发挥致病作用。近交系 SAM-P/10 菌株已被建立作为年龄相关性脑萎缩的模型。形态测量研究表明，额叶皮层（包括前额叶皮层、其他新皮层区域、梨状皮层后部、内嗅皮层前嗅核、杏仁核和尾壳核）是萎缩的易发区域。随着年龄的增长，神经元体体萎缩和大神经元丧失是 SAM 所特有的-P/10，两者都会导致大脑皮层的年龄相关性萎缩SAM-P/10。