Studies on autoantigens and pathogenesis in canine idiopathic encephalitis.

犬特发性脑炎自身抗原及发病机制的研究。

• 批准号: 16380211
• 负责人: MATSUKI Naoaki
• 金额: $ 6.34万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16380211/
• 关键词: Dogs; Autoimmunity; Necrotizing meningoencephalitis; Granulomatous meningoencephalitis; GFAP; Glutamate; EAAT; 自己抗体; グリア線維性酸性蛋白質; クローニング

1)GFAP is a common autoantigen in canine necrotizing nemingoencephalitis and granulomatous meningoencephalitis : To identify the common autoantigen(s) in canine idiopathic encephalitis, we collected cerebrospinal fluids from 40 dogs with necrotizing meningoencephalitis (NME) or granulomatous meningoencephalitis (GME). Eighty dogs with other CNS diseases were also examined. By Western blotting on canine brain proteins and MALDI-TOF-MASS, glial fibrillaly acidic protein (GFAP) was the candidate of autoantigen. In fact patients' CSFs reacted with purified bovine GFAP. These results clearly showed that GFAP is a common autoantigen in canine NME as well as in GME.2)CSFs from NME dogs inhibit glutamate uptake into normal canine astrocytes : To clarify the effect of NME or GME to glutamate homeostasis in the brain, cultured canine astrocytes were treated with CSFs from NME (GME) patients. Glutamate concentrations in the supernatants were elevated in the treated cultures, with the significant decrease in mRNAs of glutamate transporters (EAAT1 and 2). Thus, NME and GME inhibit glial glutamate uptake, which can lead to neuronal damage in the brain.

1）GFAP是犬坏死性脑膜脑炎和肉芽肿性脑膜脑炎的常见自身抗原：为了鉴定犬特发性脑炎的常见自身抗原，我们收集了40只患有坏死性脑膜脑炎（NME）或肉芽肿性脑膜脑炎（GME）的狗的脑脊液。八十只患有其他中枢神经系统疾病的狗也接受了检查。通过犬脑蛋白Western blotting和MALDI-TOF-MASS检测，胶质纤维酸性蛋白（GFAP）是候选自身抗原。事实上，患者的脑脊液与纯化的牛 GFAP 发生反应。这些结果清楚地表明，GFAP 是犬 NME 和 GME 中常见的自身抗原。2) NME 犬的 CSF 抑制正常犬星形胶质细胞摄取谷氨酸：为了阐明 NME 或 GME 对大脑中谷氨酸稳态的影响，培养犬使用 NME (GME) 患者的脑脊液处理星形胶质细胞。在处理过的培养物中，上清液中的谷氨酸浓度升高，谷氨酸转运蛋白（EAAT1和2）的mRNA显着减少。因此，NME 和 GME 会抑制胶质细胞谷氨酸的摄取，从而导致大脑神经元损伤。