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Pathological and genetic studies of cerebral degeneration in senescence-accelerated mouse

加速衰老小鼠大脑变性的病理和遗传学研究

基本信息

批准号：
13670238
负责人：
SHIMADA Atsyoshi
金额：
$ 0.9万
依托单位：
Aichi Human Service Center, Institute for Developmental Research
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670238/
关键词：
senescence-accelerated mouse brain aging genetics inclusion neurodegeneration ubiquitin QTL タウ

项目摘要

Following findings were obtained through the studies using SAMP 10 (senescence-accelerated mouse), a spontaneous model of cerebral degeneration.1. Ubiquitinated intraneuronal inclusions that affects chiefly the limbic structuresMany neurons had ubiquitinated inclusions in the brains of aged SAMP10 mice. These inclusions were different from those previously reported, but showed a similar pattern of distribution as that of neurofibrillary tangles.2. Age-related neuronal intranuclear DNA damagesTUNEL positivity of neuronal nuclei increased with advancing age in the prefrontal cortex and limbic structures in SAMP 10 mice. These TUNEL positive neurons were not apoptotic. This DNA damage was considered as a manifestation of degenerative changes associated with neuronal atrophy.3. Synaptic loss with agingRegional specificity of degenerative changes in the neuropil of SAMP10 mice was determined by quantifying synapse-related proteins. Synapses were lost from the frontal cortex by more than 50% in aged SAMP10 mice.4. Age-related changes in the dendritic complexity of prefrontal neuronsApical but not basal dendrites of the prefrontal neurons in SAMP10 mice gradually retracted toward the somata with relative preservation of dendritic complexity. The dendritic spines were lost as well.5. Creation of a large-scale colony of cross-bred miceSAMP10 mice were cross bred with SAMR1 mice, and F_1 and F_2 mice were raised up to age 16 months. Learning and memory function and brain morphology were evaluated in all of these mice. Microsatellite markers were proven to be useful to perform QTL anaysis.

通过对自发性脑变性模型SAMP 10（衰老加速小鼠）的研究，得到以下结果：主要影响边缘结构的泛素化的神经元内包涵体在老年SAMP10小鼠的大脑中，许多神经元具有泛素化的包涵体。这些包涵体与先前报道的不同，但表现出与神经原纤维缠结相似的分布模式。年龄相关性神经元核内DNA损伤samp10小鼠前额叶皮层和边缘结构神经元核unel阳性随年龄增长而增加。TUNEL阳性神经元未发生凋亡。这种DNA损伤被认为是与神经元萎缩相关的退行性改变的表现。通过定量突触相关蛋白测定SAMP10小鼠神经皮层退行性变化的区域特异性。老年SAMP10小鼠额叶皮层突触丢失超过50%。年龄相关的前额叶神经元树突复杂性变化SAMP10小鼠前额叶神经元的树突逐渐向体细胞内收缩，树突复杂性相对保留。树突棘也消失了。将amp10小鼠与SAMR1小鼠进行杂交，将F_1和F_2小鼠饲养至16月龄。对所有小鼠的学习记忆功能和脑形态进行了评估。微卫星标记可用于QTL分析。