AXONAL DEGENERATION PROMOTES ABNORMAL ACCUMULATION OF AMYLOID BETA-PROTEIN IN ASCENDING GRACILE TRACT OF GRACILE AXONAL DYSTROPHY (GAD) MOUSE
AXONAL DEGENERATION PROMOTES ABNORMAL ACCUMULATION OF AMYLOID BETA-PROTEIN IN ASCENDING GRACILE TRACT OF GRACILE AXONAL DYSTROPHY (GAD) MOUSE
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DOI：
10.1016/0006-8993(95)00729-a
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发表时间：
1995-10-16
期刊：
影响因子：
2.9
通讯作者：
KIKUCHI, T
中科院分区：
文献类型：
--
作者：
ICHIHARA, N;WU, J;KIKUCHI, T
GAD小鼠是一种自发性神经系统突变体，在延髓和脊髓的薄束中具有轴突营养不良。用免疫组织化学方法检测了正常和广泛性焦虑症小鼠薄束和背根神经节中淀粉样前体蛋白（APP-IR）和淀粉样β蛋白（A β P-IR）的免疫反应性。在4、9、18和32周龄时对小鼠进行研究。这些时期在临床上分别对应于疾病的初始、进行性、临界和终末阶段。在GAD小鼠的薄束核中，早在4周龄时，轴突和胶质细胞中的APP-IR就已增强到较高水平。GAD小鼠背根神经节APP-IR也明显增高。GAD小鼠腰髓水平背根神经节内几乎所有的初级神经元的APP免疫反应均强于正常小鼠。大约第9周，显示淀粉样β蛋白免疫反应性的细胞在薄核的轴突和胶质细胞中呈阳性，随后A β P-LR按颈、胸和腰脊髓的顺序增加。这些结果表明，GAD小鼠的初始特征是由轴突营养不良诱导的淀粉样前体蛋白的积累，然后导致淀粉样β蛋白沉积在薄束中轴突和胶质细胞的细胞质内。
The GAD mouse is a spontaneous neurological mutant with axonal dystrophy in the gracile tract of the medulla oblongata and spinal cord. The immunoreactivity of amyloid precursor protein (APP-IR) and amyloid beta-protein (A beta P-IR) was examined in the gracile tract and the dorsal root ganglia of normal and GAD mice. The mice were studied at 4, 9, 18, and 32 weeks of age. These periods correspond clinically to the initial, progressive, critical, and terminal stages of the disease, respectively. The APP-IR in both axons and glial cells was already accentuated to a higher level as early as 4 weeks of age in the gracile nucleus of GAD mouse. Similarly there was increase in APP-IR of GAD mouse in the dorsal root ganglia. Almost all of the primary neurons in the dorsal root ganglia at the lumbar cord level of GAD mouse revealed stronger APP-IR than those of normal mouse throughout all stages. The cells showing immunoreactivity for amyloid beta-protein became positive in axons and glial cells in the gracile nucleus by approximately the 9th week, and followed by an increase of A beta P-LR in order of the cervical, thoracic and lumbar spinal cords. These results suggest that the initial feature in GAD mouse is an accumulation of amyloid precursor protein induced by axonal dystrophy which then leads to a deposition of amyloid beta-protein within the cytoplasm of both axons and glial cells in the gracile tract.