Taguchi Ayako, Niwa Masayuki, Hoshi Masato, Saito Kuniaki, Masutani Teruaki, Hisamatsu Kenji, Kobayashi Kazuhiro, Hatano Yuichiro, Tomita Hiroyuki, Hara Akira
Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu, Japan.
Medical Science Division, United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu, Japan.
Neurosci Lett. 2014 Apr 3;564:120-5. doi: 10.1016/j.neulet.2014.01.051. Epub 2014 Feb 12.
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.
吲哚胺2,3-双加氧酶1（IDO1）是犬尿氨酸途径中的限速酶，该途径可将L-色氨酸转化为L-犬尿氨酸。脑心肌炎病毒（EMCV）可在包括小鼠在内的多种动物中引起急性心肌炎。此前，据报道IDO1在免疫相关疾病中具有重要的免疫调节功能。然而，IDO1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明确。我们观察到急性EMCV感染会导致小鼠小脑出现高度可重复的神经元变性。本研究的目的是确定在小鼠小脑急性EMCV感染期间IDO1的组织/细胞特异性和时间依赖性表达。在EMCV诱导的显示神经元变性的小脑病变中，小胶质细胞中IDO1上调，小胶质细胞在形态上被识别为活化，且对离子钙结合衔接分子1（Iba-1，一种在小胶质细胞中表达的蛋白质）呈阳性，尽管仅在浦肯野细胞的细胞质中检测到非常微弱的IDO1表达。在病毒接种10天后，EMCV诱导的小脑病变中未观察到GFAP免疫染色，尽管病变周围的许多反应性星形胶质细胞对GFAP呈强阳性免疫染色。因此，IDO1表达可能会影响EMCV诱导的小脑神经元变性。
