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The study of neuropathogenesis in the developing brain disorders induced by viral infection

病毒感染引起的脑部疾病的神经发病机制研究

基本信息

批准号：
12470054
负责人：
TSUTSUI Yoshihiro
金额：
$ 7.36万
依托单位：
Hamamatsu University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12470054/
关键词：
viral encephalopathy cytomegalovirus transgenic mice brain slice culture brain disorder neural progenitor cells neural stem cells トランスゲニックマウス

项目摘要

We investigated the effects of murine cytomegalovirus (MCMV) infection on the developing mouse brain in terms of susceptible cells and age-related resistance. Mouse brain slices at different development stages were infected with recombinant MCMV in which the lacZ gene was inserted into a late gene. The ventricular zone (VZ) and cortical marginal region were the sites most susceptible to MCMV infection, and the susceptibility declined with the development of the brain. Immunohistochemical staining showed that the virus-susceptible cells were positive for GFAP, nestin and Musashi-1, suggesting the susceptible cells in the VZ are glial progenitor cells. These results suggest that the amount of immature glial cells in the developing brain may be closely associated with the susceptibility of the brain to CMV infection in humans.We examined the reactivation of latent murine CMV (MCMV) infection in the mouse brain by their transfer to brain slice culture. We infected neonatal and young adult mice intracerebrally with recombinant MCMV. The brains were removed 6 months after infection, and used to prepare brain slices that were then cultured for up to 4 weeks. X-Gal-positive cells were observed in marginal regions of the brains or immature neural cells in the ventricular walls. Immunohistochemical staining showed that the X-Gal-positive reactivated cells were neural stem/progenitor cells. These results suggest that brain disorders may occur long after infection by reactivation of latent infection in the immature neural cells.

我们从易感细胞和与年龄相关的抵抗力方面研究了小鼠巨细胞病毒(MCMV)感染对发育中的小鼠脑的影响。用重组MCMV感染不同发育阶段的小鼠脑片，将LacZ基因插入到晚期基因中。脑室带(VZ)和皮质边缘区是MCMV感染的易感部位，且随着大脑发育，易感性下降。免疫组织化学染色显示病毒易感细胞GFAP、Nestin和Musashi-1阳性，提示VZ内的易感细胞为神经胶质前体细胞。这些结果表明，发育中脑内未成熟胶质细胞的数量可能与人脑对CMV感染的易感性密切相关。我们通过将小鼠潜伏的CMV(MCMV)转移到脑片培养上，研究了小鼠脑内潜伏的CMV感染的重新激活。用重组MCMV脑内感染新生小鼠和幼年小鼠。感染6个月后取出大脑，用来准备脑片，然后培养长达4周。X-Gal阳性细胞见于脑边缘区域或脑室壁未成熟神经细胞。免疫组织化学染色显示X-Gal阳性再激活细胞为神经干/祖细胞。这些结果表明，脑部疾病可能在感染后很长一段时间内通过重新激活未成熟神经细胞中的潜伏感染而发生。