Kakizaki Masatoshi, Watanabe Rihito
Department of Bioinformatics, Graduate School of Engineering, Soka University, Hachioji, Tokyo, Japan.
Neuropathology. 2017 Oct;37(5):398-406. doi: 10.1111/neup.12386. Epub 2017 May 11.
The apoptosis of pyramidal neurons in CA2 and CA3 subregions of the hippocampus is induced after infection with Mu-3 virus (Mu-3), a neuropathogenic strain of the JHM virus (JHMV), at 4-5 days post-inoculation (dpi). The viral antigens in the hippocampus are mainly found in the CD11b-positive cells distributed in the stratum oriens located outside the pyramidal layer, and only a few pyramidal neurons are infected. Furthermore, the apoptotic cells, indicated as showing caspase 3 (Cas3) activation, consist of a high number of uninfected cells. Therefore, it is considered that the apoptotic lesions occur through the indirect effects of infection, and not as a result of direct infection with Mu-3, similar to the reported neuronal apoptosis in the hippocampus after other types of infection. The apoptosis in the pyramidal neurons is accompanied by various types of proinflammatory cytokines depending on the causative agents. Thus, the local expression of proinflammatory cytokines was studied, revealing no correlation in the distribution of cytokine expression with the subregions showing apoptosis. However, the anti-inflammatory cytokine IL-10 was produced by pyramidal neurons of CA2 and CA3 at 3 dpi when there is no destructive change or viral invasion in the hippocampus.
接种后4 - 5天,感染穆-3病毒(Mu-3)(JHM病毒(JHMV)的一种神经致病株)会诱导海马体CA2和CA3亚区锥体细胞凋亡。海马体中的病毒抗原主要存在于分布在锥体细胞层外的原层中的CD11b阳性细胞中,只有少数锥体细胞被感染。此外,显示半胱天冬酶3(Cas3)激活的凋亡细胞由大量未感染细胞组成。因此,人们认为凋亡性病变是通过感染的间接作用发生的,而不是Mu-3直接感染的结果,这与其他类型感染后海马体中报道的神经元凋亡情况类似。锥体细胞的凋亡伴随着取决于病原体的各种促炎细胞因子。因此,研究了促炎细胞因子的局部表达,结果显示细胞因子表达的分布与出现凋亡的亚区之间没有相关性。然而,在接种后3天,当海马体没有破坏性变化或病毒入侵时,CA2和CA3的锥体细胞会产生抗炎细胞因子IL-10。