Brain slice culture for analysis of developmental brain disorders with special reference to congenital cytomegalovirus infection.
Brain slice culture for analysis of developmental brain disorders with special reference to congenital cytomegalovirus infection.
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DOI：
10.1111/j.1741-4520.2003.tb01034.x
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发表时间：
2003-06-01
影响因子：
1.3
通讯作者：
Tsutsui, Yoshihiro
中科院分区：
文献类型：
--
作者：
Kawasaki, Hideya;Tsutsui, Yoshihiro
巨细胞病毒（CMV）是中枢神经系统（CNS）先天性异常的最重要的感染性原因，从致命的巨细胞包涵体疾病到功能性脑疾病。脑疾病的表型和程度取决于发育阶段的感染时间、毒力、感染途径和细胞的病毒易感性。中枢神经系统CMV感染的发病机制似乎与神经迁移、神经死亡、脑细胞组成和免疫系统密切相关。为了了解这种疾病的复杂机制，我们使用了器官型脑切片培养。在脑切片培养系统中，观察到CMV感染的神经元细胞的迁移，这反映了体内的感染动力学。脑室下区和边缘区的神经前体细胞或神经胶质未成熟细胞对小鼠巨细胞病毒（MCMV）感染最敏感。随着年龄的增长，未成熟胶质细胞的数量减少，敏感性下降。在脑片培养中，未成熟的胶质细胞在长时间孵育期间增殖，并且对MCMV感染的易感性也随着这些细胞的增殖而增加。在任何长时间孵育期间，来自免疫受损小鼠（Beige-SCID小鼠）的脑切片意外地显示出比免疫活性小鼠更低的易感性。这些结果表明，未成熟胶质细胞的数量可能决定了CMV感染的易感性，独立于免疫系统。我们从脑切片培养的角度回顾了CMV感染脑的最新研究结果，以及该系统可能成为研究脑先天性异常机制的有用方法的可能性。
Cytomegalovirus (CMV) is the most significant infectious cause of congenital abnormalities of the central nervous system (CNS) with variation from the fatal cytomegalic inclusion disease to functional brain disorder. The phenotype and degree of the brain disorder depends on infection time during the developing stage, virulence, route of infection and the viral susceptibility of the cells. The pathogenesis of the CMV infection to the CNS seems to be strongly related to neural migration, neural death, cellular compositions and the immune system of the brain. To understand the complex mechanism of this disorder, we used organotypic brain slice cultures. In the brain slice culture system, migration of CMV-infected neuronal cells was observed, which reflects infectious dynamics in vivo. Neural progenitor cells or glial immature cells in the subventricular zone and marginal area are most susceptible to murine cytomegalovirus (MCMV) infection in this system. The susceptibility declined as the number of immature glial cells decreased with age. The immature glial cells proliferated in brain slice cultures during prolonged incubation, and the susceptibility to MCMV infection also increased in association with the proliferation of these cells. The brain slice from an immunocompromised mouse (Beige-SCID mouse) unexpectedly showed lower susceptibility than that of an immunocompetent mouse during any prolonged incubation. These results suggest that the number of immature glial cells might determine the susceptibility of CMV infection to the brain, independent of the immune system. We reviewed recent findings of CMV infection to the brain from the perspective of brain slice cultures and the possibility that this system could be a useful method to investigate mechanisms of congenital anomaly of the brain.