Mechanism of neuronal cell death in the developing mouse brain after intrauterine infection with cytomegalovirus

巨细胞病毒宫内感染后发育中小鼠大脑神经元细胞死亡的机制

• 批准号: 10670284
• 负责人: TSUTSUI Yoshihiro
• 金额: $ 2.3万
• 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 (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670284/
• 关键词: Cytomegalovirus; Apoptosis; neuronal cell death; Intrauterine infection

Cytomegalovirus (CMV) is the most common cause of congenital infection, resulting in birth defects such as microcephaly. In this study, we found that apoptosis is induced in the developing mouse brain infected with murine cytomegalovirus (MCMV) in an association with neuronal cell loss. With the combination of the terminaldeoxynucleotidyl transferase-mediated dUTP nick edn labeling (TUNEL) technique and immunohistochemical staining. A few percent TUNEL-positive cells were double-labeled with neuronal glial markers, while more than 30% of microglial cells were turned into apoptosis, presumably the consequence of engulfment of the neuronal apoptotic cells. In the primary neuronal cultures, MCMV infection inhibited the induction of apoptosis either by serum deprivation or glutamate treatment. The induction and blocking of neuronal apoptosis by virus infection may be important for morphological and functional disorders in the congenital CMV infection.

巨细胞病毒（CMV）是先天性感染的最常见原因，导致出生缺陷，如小头畸形。在这项研究中，我们发现，细胞凋亡是诱导小鼠大脑发育感染鼠巨细胞病毒（MCMV）与神经细胞损失。采用末端脱氧核苷酸转移酶介导的dUTP缺口标记（TUNEL）技术和免疫组化染色相结合的方法。少数百分比的TUNEL阳性细胞与神经胶质细胞标记物双标记，而超过30%的小胶质细胞变成凋亡，推测是神经元凋亡细胞吞噬的结果。在原代神经元培养中，MCMV感染抑制了血清剥夺或谷氨酸处理诱导的细胞凋亡。病毒感染诱导和阻断神经细胞凋亡可能对先天性CMV感染的形态和功能障碍具有重要意义。

项目成果

筒井祥博: "サイトメガロウイルスによる脳発達障害の発生機序"病理と臨床17臨時増刊号-日本人の病気と病理学. 17. 332 (1999)

Yoshihiro Tsutsui：“巨细胞病毒引起的脑发育障碍的发展机制”病理学和临床研究 17 特刊 - 日本疾病和病理学 17. 332 (1999)。

Tsutsui Y., Li R-Y, Baba S., Kosugi I., Shinmura Y.: "A mouse model of congenital cytomegalovirus infection"The 3rd China-Japan International Congress of Virology. (1999)

Tsutsui Y.，Li R-Y，Baba S.，Kosugi I.，Shinmura Y.：“先天性巨细胞病毒感染的小鼠模型”第三届中日国际病毒学大会。

筒井祥博: "Latent Infection Pathology(LIP)第4巻"菜根出版(in press).

Yoshihiro Tsutsui：“潜伏感染病理学 (LIP) 第 4 卷”Nane Publishing（正在印刷中）。

Aiba-Masago S., Baba S., Li R-Y, Shinmura Y., Kosugi I., Arai Y., Nishimura M., Tsutsui Y.: "Murine cytomegalovirus immediate-early promoter directs astrocyte-specific expression in transgenic mice"American Journal of Pathology. 154(3). 735-743 (1999)

Aiba-Masago S.、Baba S.、Li R-Y、Shinmura Y.、Kosugi I.、Arai Y.、Nishimura M.、Ttsutsui Y.：“鼠巨细胞病毒立即早期启动子指导转基因小鼠中星形胶质细胞特异性表达”美国

Kosugi I., Shinmura Y., Kawasaki H., Arai Y., Li R-Y, Baba S., Tsutsui Y.: "Cytomegalovirus infection suppresses growth of the central nervous system stem cells from mouse embryos and inhibits their neuronal differentiation in vitro"Laboratory Investigati

Kosugi I.、Shinmura Y.、Kawasaki H.、Arai Y.、Li R-Y、Baba S.、Ttsutsui Y.：“巨细胞病毒感染抑制小鼠胚胎中枢神经系统干细胞的生长，并抑制其体外神经元分化”