Saito Y, Oka A, Mizuguchi M, Motonaga K, Mori Y, Becker L E, Arima K, Miyauchi J, Takashima S
Department of Clinical Laboratory, National Center Hospital for Mental, Nervous and Muscular Disorders, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.
Acta Neuropathol. 2000 Dec;100(6):654-64. doi: 10.1007/s004010000230.
We studied the expression of Down's syndrome cell adhesion molecule (DSCAM) in Down's syndrome (DS) and control brains, using antisera against peptide fragments of DSCAM. On Western blots of human, mouse and rat brain homogenates, the antisera recognized a product at approximately 200 kDa. In the brain of a 2-year-old patient with DS, Western blotting revealed an overexpression of DSCAM compared to an age-matched control. Immunohistochemistry demonstrated DSCAM in the cerebral and cerebellar white matter of both control and DS subjects, in accordance with the temporal and spatial sequence of myelination. In DS brains, immunoreactivity for DSCAM, compared to that for controls, was enhanced in the Purkinje cells at all ages, and in the cortical neurons during adulthood. In demented DS patients, DSCAM immunoreactivity was observed in the core and periphery of senile plaques. The pattern of DSCAM expression suggests that it may play a role as an adhesion molecule regulating myelination. The overexpression of DSCAM may also play a role in the mental retardation and the precocious dementia of DS patients, although the mechanism of neuronal dysfunction is undetermined.
我们使用针对唐氏综合征细胞粘附分子（DSCAM）肽段的抗血清，研究了唐氏综合征（DS）患者及对照者大脑中DSCAM的表达情况。在人、小鼠和大鼠脑匀浆的蛋白质免疫印迹分析中，该抗血清识别出一条约200 kDa的条带。在一名2岁DS患者的大脑中，蛋白质免疫印迹分析显示与年龄匹配的对照相比，DSCAM表达上调。免疫组织化学显示，对照者和DS患者的大脑和小脑白质中均有DSCAM表达，与髓鞘形成的时间和空间顺序一致。在DS患者大脑中，与对照相比，各年龄段的浦肯野细胞以及成年期的皮质神经元中DSCAM的免疫反应性均增强。在患有痴呆症的DS患者中，在老年斑的核心和周边观察到DSCAM免疫反应性。DSCAM的表达模式表明，它可能作为一种调节髓鞘形成的粘附分子发挥作用。尽管神经元功能障碍的机制尚不清楚，但DSCAM的过表达可能也在DS患者的智力发育迟缓及过早出现的痴呆中起作用。
