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Please use this identifier to cite or link to this item: http://hdl.handle.net/10271/3145

Title: Aberrant fetal macrophage/microglial reactions to cytomegalovirus infection
Other Titles: サイトメガロウイルス感染に対する胎生期マクロファージ/ミクログリア異常反応
Authors: Suzuki, Makiko
鈴木, 万幾子
Issue Date: 28-Jul-2014
Publisher: American Neurological Association
Abstract: Objective: Congenital cytomegalovirus (CMV) infection is the leading viral cause of neurodevelopmental disorders in humans, with the most severe and permanent sequelae being those affecting the cerebrum. As the fetal immune reactions to congenital CMV infection in the brain and their effects on cerebral development remain elusive, our aim was to investigate primitive innate immunity to CMV infection and its effects on cerebral corticogenesis in a mouse model for congenital CMV infection using a precise intraplacental inoculation method. Methods: At 13.5 embryonic days (E13.5), pregnant C57BL/6 mice were intraplacentally infected with murine CMV (MCMV). Placentas and fetal organs were collected at 1, 3, and 5 days postinfection and analyzed. Results: MCMV antigens were found frequently in perivascular macrophages, and subsequently in neural stem/progenitor cells (NSPCs). With increased expression of inducible nitric oxide synthase and proinflammatory cytokines, activated macrophages infiltrated into the infectious foci. In addition to the infected area, the numbers of both meningeal macrophages and parenchymal microglia increased even in the uninfected areas of MCMV-infected brain due to recruitment of their precursors from other sites. A bromodeoxyuridine (BrdU) incorporation experiment demonstrated that MCMV infection globally disrupted the self-renewal of NSPCs. Furthermore, BrdU-labeled neurons, particularly Brn2+ neurons of upper layers II/III in the cortical plate, decreased in number significantly in the MCMV-infected E18.5 cerebrum. Interpretation: Brain macrophages are crucial for innate immunity during MCMV infection in the fetal brain, while their aberrant recruitment and activation may adversely impact on the stemness of NSPCs, resulting in neurodevelopmental disorders.
Description: 浜松医科大学学位論文 医博第723号(平成28年3月14日)
URI: http://hdl.handle.net/10271/3145
DOI: Info:doi/10.1002/acn3.88
PubMed ID: info:pmid/25356429
Academic Degrees and number: 13802甲第723号
Degree-granting date: 2016-03-14
Degree name: 博士(医学)
Degree-granting institutions: 浜松医科大学
Appears in Collections:2010 博士(論文)

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