Arai Y, Uchida Y, Takashima S
Department of Mental Retardation and Birth Defect Research; National Institute of Neuroscience; National Center of Neurology and Psychiatry; Tokyo, Japan.
Pediatr Neurol. 1997 Sep;17(2):134-8. doi: 10.1016/s0887-8994(97)00085-4.
Growth inhibitory factor, a new metallothioneinlike protein, was investigated at postmortem examination in the brains of 18 patients with Down syndrome ranging in age from 18 weeks gestation to 50 years of age and in 20 age-matched normal controls by developmental immunohistochemistry. In the frontal cortex of both Down syndrome patients and controls, growth inhibitory factor immunoreactivity was localized in the cell bodies and processes of protoplasmic astrocytes from 18 weeks gestation, and these immunoreactive processes formed so dense a meshwork in the gray matter that they outlined neuronal perikarya as negative contours in the brain at age more than 16 years. The number of growth inhibitory factor-immunoreactive astrocytes exhibited a greater increase in layer 3 than in layer 2 in controls from 37 weeks gestation to 7 months of age, although there was no difference in the growth inhibitory factor-positive cell number between layers 2 and 3 in young Down syndrome patients. Therefore, growth inhibitory factor in astrocytes may be correlated with dendritic maturation of neurons. On the other hand, growth inhibitory factor-immunoreactive astrocytes in layer 2, where senile plaques are abundant, were smaller than those in layer 3 in adult Down syndrome patients from age 32 years. When senile plaques began to immunoreact with the amyloid precursor protein, the number of growth inhibitory factor-immunoreactive astrocytes decreased around senile plaques in elderly Down syndrome brains with the Alzheimer type of dementia. On the contrary, the number of glial fibrillary acidic protein-immunoreactive astrocytes around senile plaques increased. This loss of growth inhibitory factor around senile plaques may be correlated with neuronal loss or degeneration and lead to sprouting responses which may be involved in the formation of senile plaques.
生长抑制因子是一种新的类金属硫蛋白，我们通过发育免疫组织化学方法，对18例年龄从妊娠18周至50岁的唐氏综合征患者及20例年龄匹配的正常对照者的大脑进行了尸检研究。在唐氏综合征患者和对照者的额叶皮质中，从妊娠18周起，生长抑制因子免疫反应性就定位于原浆性星形胶质细胞的胞体和突起中，在16岁以上的大脑灰质中，这些免疫反应性突起形成了如此密集的网络，以至于它们将神经元胞体勾勒为负轮廓。在妊娠37周龄至7月龄的对照者中，生长抑制因子免疫反应性星形胶质细胞的数量在第3层的增加比在第2层的更大，尽管在年轻的唐氏综合征患者中，第2层和第3层之间的生长抑制因子阳性细胞数量没有差异。因此，星形胶质细胞中的生长抑制因子可能与神经元的树突成熟有关。另一方面，在32岁的成年唐氏综合征患者中，富含老年斑的第2层中的生长抑制因子免疫反应性星形胶质细胞比第3层中的小。当老年斑开始与淀粉样前体蛋白发生免疫反应时，在患有阿尔茨海默型痴呆的老年唐氏综合征患者大脑中，老年斑周围的生长抑制因子免疫反应性星形胶质细胞数量减少。相反，老年斑周围的胶质纤维酸性蛋白免疫反应性星形胶质细胞数量增加。老年斑周围生长抑制因子的这种丧失可能与神经元的丧失或退化有关，并导致可能参与老年斑形成的发芽反应。
