Nordlund M L, Rizvi T A, Brannan C I, Ratner N
Department of Cell Biology, Neurobiology and Anatomy, University of Cincinnati College of Medicine, OH 45267-0521, USA.
J Neuropathol Exp Neurol. 1995 Jul;54(4):588-600. doi: 10.1097/00005072-199507000-00013.
Patients with type 1 neurofibromatosis (NF1) have mutations in the gene encoding the protein neurofibromin. Immunocytochemistry on sections of cortex and cerebellum of unaffected and NF1 individuals and wild-type and NF1-deficient mice showed that the distribution of neurofibromin was similar to that reported for rat. However, dystrophic neurofibromin-expressing neurons were found in human but not rodent brain. Intensity of anti-neurofibromin reactivity was reduced in NF1-deficient mice but not in human brains. GFAP was upregulated in three NF1 brains studied by immunocytochemistry; a 4-18-fold increase in GFAP levels was documented by Western blot analysis in three brains. GFAP content/cell and the number of GFAP-immunoreactive astrocytes was increased in NF1 brains as compared to the controls. These results suggest that mutations in the NF1 gene do not grossly alter the pattern of neurofibromin expression, but activation of astrocytes may be common in NF1. Presence of degenerative debris in one of two brains using the cupric silver method suggests that degeneration is not always detectable in NF1 brains.
1型神经纤维瘤病（NF1）患者的神经纤维瘤蛋白编码基因发生了突变。对未受影响个体和NF1个体以及野生型和NF1缺陷型小鼠的皮质和小脑切片进行免疫细胞化学分析，结果显示神经纤维瘤蛋白的分布与大鼠的报道相似。然而，在人类大脑中发现了表达营养不良性神经纤维瘤蛋白的神经元，而在啮齿动物大脑中未发现。在NF1缺陷型小鼠中，抗神经纤维瘤蛋白反应的强度降低，但在人类大脑中未降低。通过免疫细胞化学分析，在研究的三个NF1大脑中，胶质纤维酸性蛋白（GFAP）上调；通过蛋白质印迹分析，在三个大脑中记录到GFAP水平增加了4至18倍。与对照组相比，NF1大脑中GFAP含量/细胞以及GFAP免疫反应性星形胶质细胞的数量增加。这些结果表明，NF1基因的突变不会严重改变神经纤维瘤蛋白的表达模式，但星形胶质细胞的激活在NF1中可能很常见。使用铜银法在两个大脑中的一个中发现了退行性碎片，这表明在NF1大脑中并不总是能检测到退变。
