Indoleamine 2,3-dioxygenase 1 is upregulated in activated microglia in mice cerebellum during acute viral encephalitis
Indoleamine 2,3-dioxygenase 1 is upregulated in activated microglia in mice cerebellum during acute viral encephalitis
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DOI：
10.1016/j.neulet.2014.01.051
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发表时间：
2014-04-03
影响因子：
2.5
通讯作者：
Hara, Akira
中科院分区：
文献类型：
--
作者：
Taguchi, Ayako;Niwa, Masayuki;Hara, Akira
吲哚胺2，3-双加氧酶1（IDO 1）是犬尿氨酸途径中将L-色氨酸转化为L-犬尿氨酸的限速酶。脑心肌炎病毒（Encephalomyocarditis virus，EMCV）可引起包括小鼠在内的多种动物的急性心肌炎。此前，IDO 1已被报道在免疫相关疾病中具有重要的免疫调节功能。然而，IDO 1在中枢神经系统急性病毒感染后的病理生理作用尚未完全了解。我们观察到急性EMCV感染导致小鼠小脑高度可重复的神经元变性。本研究的目的是确定IDO 1的组织/细胞特异性和时间依赖性的表达在急性EMCV感染小鼠小脑。IDO 1在小胶质细胞中上调，这被认为是激活形态和阳性的离子钙结合衔接分子1（Iba-1），蛋白质表达的小胶质细胞，在EMCV诱导的小脑病变显示神经元变性，虽然非常弱的表达IDO 1只在浦肯野细胞的细胞质中检测。在EMCV诱导的小脑病变中没有观察到GFAP免疫染色，尽管病毒接种后10天病变周围的许多反应性星形胶质细胞显示GFAP免疫染色强阳性。因此，IDO 1表达可能影响EMCV诱导的小脑神经元变性。(C)2014爱思唯尔爱尔兰有限公司版权所有。
Indoleamine 2,3-dioxygenase1 (IDO1) is the rate-limiting enzyme in the kynurenine pathway that converts L-tryptophan to L-kynurenine. Encephalomyocarditis virus (EMCV) can cause acute myocarditis in various animals including mice. Previously, IDO1 has been reported to have an important immunomodulatory function in immune-related diseases. However, the pathophysiological roles of IDO1 following acute viral infection of central nervous system are not fully understood. We observed that acute EMCV infection leads to a highly reproducible neuronal degeneration in mouse cerebellum. The goal of this study is to determine tissue/cell-specific and time-dependent expressions of IDO1 during acute EMCV infection in mouse cerebellum. IDO1 was up-regulated in microglia, which was recognized to be activated morphologically and positive for ionized calcium-binding adapter molecule 1 (Iba-1), a protein expressed in microglia, within EMCV-induced cerebellar lesions showing neuronal degeneration although the very weak expression of IDO1 is detected only in cytoplasm of Purkinje cells. No GFAP immunostaining was observed in EMCV-induced cerebellar lesions although many reactive astrocytes surrounding the lesions showed strongly positive immunostaining for GFAP 10 days after the viral inoculation. Thus, IDO1 expression may affect EMCV-induced neuronal degeneration in cerebellum. (C) 2014 Elsevier Ireland Ltd. All rights reserved.