PDF(Pubmed)
Abstract：
Aquaporin-4 (AQP4) expression is associated with the development of congenital hydrocephalus due to its structural role in the ependymal membrane. Gene expression analysis of periaqueductal tissue in AQP4-knockout (KO) mice at 11 days of age (P11) showed a modification in ependymal cell adhesion and ciliary protein expression that could alter cerebrospinal fluid homeostasis. A microglial subpopulation of CD11c+ cells was overexpressed in the periaqueductal tissue of mice that did not develop hydrocephalus, suggesting a possible protective effect. Here, we verified the location of this CD11c+ expression in the corpus callosum (CC) and cerebellum of AQP4-KO mice and analysed its time course. Immunofluorescence labelling of the CD11c protein in the CC and cerebellum of WT and KO animals at P3, P5, P7 and P11 confirmed an expanded presence of these cells in both tissues of the KO animal; CD11c+ cells appeared at P3 and reached a peak at P11, whereas in the WT animal, they appeared at P5, reached their peak at P7 and were undetectable by P11. The gene expression analysis in the CC samples at P11 confirmed the presence of CD11c+ microglial cells in this tissue. Among the more than 4000 overexpressed genes, Spp1 stood out with the highest differential gene expression (≅600), with other genes, such as Gpnmb, Itgax, Cd68 and Atp6v0d2, also identified as overexpressed. Therefore, CD11c+ cells appear to be necessary for normal corpus callosum development during postnatal life, and the absence of AQP4 prolonged its expression in this tissue.
摘要：
水通道蛋白4（AQP4）的表达与先天性脑积水的发展有关，因为它在室管膜中具有结构作用。在11日龄（P11）的AQP4敲除（KO）小鼠中，导水管周围组织的基因表达分析显示，室管膜细胞粘附和睫状蛋白表达发生变化，可以改变脑脊液稳态。CD11c+细胞的小胶质细胞亚群在未发生脑积水的小鼠的导水管周围组织中过表达，表明可能的保护作用。这里,我们验证了AQP4-KO小鼠call体（CC）和小脑中CD11c表达的位置，并分析了其时程。在P3，P5，P7和P11时，WT和KO动物的CC和小脑中CD11c蛋白的免疫荧光标记证实了这些细胞在KO动物的两个组织中的扩增存在；CD11c细胞出现在P3并在P11达到峰值，而在WT动物中，它们出现在P5，在P7达到峰值，P11检测不到。在P11的CC样品中的基因表达分析证实了该组织中CD11c+小胶质细胞的存在。在4000多个过表达基因中，Spp1以最高的差异基因表达脱颖而出（600），与其他基因，例如Gpnmb，伊加克斯,Cd68和Atp6v0d2也被鉴定为过表达。因此,CD11c+细胞似乎是出生后正常call体发育所必需的，AQP4的缺失延长了其在该组织中的表达。
