Taguchi Ayako, Hara Akira, Saito Kuniaki, Hoshi Masato, Niwa Masayuki, Seishima Mitsuru, Mori Hideki
Department of Tumor Pathology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, Japan.
Brain Res. 2008 Jun 27;1217:78-85. doi: 10.1016/j.brainres.2008.02.067. Epub 2008 Mar 4.
Indoleamine 2,3-dioxygenase (IDO) is the rate-limiting enzyme in the kynurenine pathway that converts L-tryptophan to L-kynurenine. Transient forebrain ischemia initiates a series of cellular events that lead to the delayed neuronal degeneration of several brain regions. The goal of this study was to determine the localization of IDO in gerbil brain, and analyze the spatiotemporal expression of IDO in a transient forebrain ischemic model. Expression of IDO in the normal gerbil brain was observed by using immunohistochemistry. Time-course of the expression of IDO following transient forebrain ischemic gerbils was examined by immunohistochemistry, combined with hematoxylin and eosin staining for morphological analysis, and in situ terminal dUTP-biotin nick end labeling of DNA fragments (TUNEL) method. In normal gerbils, IDO immunostaining was observed in thalamus, hypothalamus and amygdaloid nucleus. IDO expression was negative in the cingulate cortex, hippocampal CA1 region and parietal cortex. Following transient ischemia, we observed a time-dependent increase of IDO expression in CA1, cingulate cortex and hypothalamus. The peak of IDO expression in CA1 and cingulate cortex occurred at 48 h after ischemic insult and diminished by 2 weeks. TUNEL staining was observed only in the CA1 region at 72 and 96 h after transient ischemia. Thus, IDO protein is present in specific regions in gerbil brain, and dynamic changes of IDO expression was observed in some neurons following transient ischemia.
吲哚胺2,3-双加氧酶（IDO）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。短暂性前脑缺血引发一系列细胞事件，导致多个脑区出现延迟性神经元变性。本研究的目的是确定IDO在沙鼠脑中的定位，并分析IDO在短暂性前脑缺血模型中的时空表达。通过免疫组织化学观察IDO在正常沙鼠脑中的表达。采用免疫组织化学、苏木精-伊红染色进行形态学分析以及DNA片段原位末端脱氧尿苷三磷酸生物素缺口末端标记（TUNEL）法，检测短暂性前脑缺血沙鼠中IDO表达的时间进程。在正常沙鼠中，在丘脑、下丘脑和杏仁核中观察到IDO免疫染色。在扣带回皮质、海马CA1区和顶叶皮质中，IDO表达为阴性。短暂性缺血后，我们观察到CA1区、扣带回皮质和下丘脑中IDO表达呈时间依赖性增加。CA1区和扣带回皮质中IDO表达的峰值在缺血损伤后48小时出现，并在2周时减弱。短暂性缺血后72小时和96小时，仅在CA1区观察到TUNEL染色。因此，IDO蛋白存在于沙鼠脑的特定区域，并且在短暂性缺血后，一些神经元中观察到IDO表达的动态变化。
