Developmental changes revealed by immunohistochemical markers in human cerebral cortex

Developmental changes revealed by immunohistochemical markers in human cerebral cortex
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DOI:
10.1093/cercor/6.6.794
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发表时间:
1996-11-01
期刊:
影响因子:
3.7
通讯作者:
Shatz, CJ
Shatz, CJ
中科院分区:
医学2区
文献类型:
--
作者:
Honig, LS;Herrmann, K;Shatz, CJ

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发育中的人类大脑皮层有一个特别宽的基底区,这是一个短暂的区域,关键的细胞间相互作用在其中发生。为了进一步了解亚板在人脑发育中的作用,我们研究了孕14周至产后9个月发育中的视觉皮层中某些神经元(GAP-43、MAP-2、小白蛋白)和星形胶质(vimentin、GFAP)标志物的免疫组织化学表达。在14-22周时,对GAP-43(一种参与轴突生长的蛋白)的免疫反应在基底区和边缘区以及靠近心室区的辐射纤维中最为突出;22-42周时,成熟皮质板中可见GAP-43免疫反应纤维。微管相关蛋白MAP-2的免疫反应性在14周时出现在分化的皮质板中,但在22-42周时在分化神经元的体细胞和树突中最为突出,特别是边缘区的Cajal-Retzius神经元、亚板神经元和形成皮质层的神经元5。小白蛋白免疫反应性直到26周才出现,染色的神经元在第6层和上亚板中呈稀疏的细胞带。Vimentin和GFAP对分化的神经细胞无染色作用。Vimentin免疫反应性在神经上皮细胞和放射状胶质细胞中早期出现,在35周后下降,同时在放射状胶质细胞和成熟星形细胞中GFAP免疫反应性增加。我们的研究结果表明,尽管发育中的人类新皮层具有更大的复杂性,但分子标记的时空表达模式与非人类灵长类动物、食肉动物和啮齿动物相似。这些蛋白质标记物应该在发育分期中被证明是有用的,并为检查先天性大脑发育障碍提供了一个框架。
The developing human cerebral cortex is distinguished by a particularly wide subplate, a transient zone in which crucial cell-cell interactions occur. To further understand the role of the subplate in human brain development, we have studied the immunohistochemical expression of certain neuronal (GAP-43, MAP-2, parvalbumin) and astroglial (vimentin, GFAP) markers in the developing visual cortex from gestational ages of 14 weeks to 9 months post-term. At 14-22 weeks, immunoreactivity to GAP-43, a protein involved in axonal outgrowth, was most prominent in the subplate and marginal zone neuropil and in the fibers of the radiations running near the ventricular zone; at 22-42 weeks, GAP-43 immunoreactive fibers were observed in the maturing cortical plate. Immunoreactivity for the microtubule-associated protein MAP-2 was present in the differentiating cortical plate at 14 weeks, but at 22-42 weeks was most prominent in the somata and dendrites of differentiated neurons, particularly the Cajal-Retzius neurons of the marginal zone, in neurons of the subplate and in those forming cortical layer 5. Parvalbumin immunoreactivity did not appear until 26 weeks, when stained neurons were in a sparse band of cells in layer 6 and upper subplate. Vimentin and GFAP did not stain differentiated neuronal cells. Vimentin immunoreactivity appeared early in neuroepithelial and radial glial cells, decreasing after 35 weeks, with a concomitant increase in GFAP immunoreactivity in radial glial and maturing astrocytic cells. Our results show that despite the greater complexity of the developing human neocortex, molecular markers are expressed in spatial and temporal patterns similar to those observed in non-human primates, carnivores and rodents. These protein markers should prove useful in developmental staging, and in providing a framework in which to examine congenital disorders of cerebral development.