{"created":"2023-05-15T15:18:29.285277+00:00","id":4881,"links":{},"metadata":{"_buckets":{"deposit":"3d2e12aa-108e-4f03-80d8-08642f8eecad"},"_deposit":{"created_by":12,"id":"4881","owners":[12],"pid":{"revision_id":0,"type":"depid","value":"4881"},"status":"published"},"_oai":{"id":"oai:obihiro.repo.nii.ac.jp:00004881","sets":["6:8"]},"author_link":["6814"],"item_3_alternative_title_1":{"attribute_name":"その他（別言語等）のタイトル","attribute_value_mlt":[{"subitem_alternative_title":"Pathologic investigations on Trypanosoma equiperdum naturally infected horses and experimentally infected mice","subitem_alternative_title_language":"en"}]},"item_3_date_granted_12":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2023-03-20"}]},"item_3_degree_grantor_10":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_language":"ja","subitem_degreegrantor_name":"帯広畜産大学"}],"subitem_degreegrantor_identifier":[{"subitem_degreegrantor_identifier_name":"10105","subitem_degreegrantor_identifier_scheme":"kakenhi"}]}]},"item_3_degree_name_9":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士（獣医学）","subitem_degreename_language":"ja"}]},"item_3_description_11":{"attribute_name":"学位授与年度","attribute_value_mlt":[{"subitem_description":"2022","subitem_description_type":"Other"}]},"item_3_description_18":{"attribute_name":"フォーマット","attribute_value_mlt":[{"subitem_description":"application/pdf","subitem_description_type":"Other"}]},"item_3_description_7":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Dourine is a protozoan disease in equids caused by infection with Trypanosoma equiperdum. T. equiperdum is transmitted by coitus, and affected horses manifest various\nclinical signs during the long-term clinical course of 1-2 months to several years. Since the mortality of affected horses is more than 50%, dourine causes significant economic damage to horse industry in developing countries. However, there is lack of studies aimed to elucidate the parasite strategies of T. equiperdum and the pathogenesis of various clinical signs and lesions observed in dourine affected horses. Therefore, the pathogenesis of dourine remains largely unknown. In human sleeping sickness caused by T. brucei rhodesiense and T. b. gambiense, pathological and parasitological studies of spontaneous cases and various multi-faceted murine infection models have been contributed to elucidate the pathogenesis of human sleeping sickness. The objective of the present studies was to elucidate the pathogenesis of dourine and the parasitic strategy of T. equiperdum, which remains largely unknown.\nIn chapter I, I conducted immunohistochemical study of peripheral neuritis observed in dourine affected horses. In chapter II and III, I have established mouse infection models that reproduce some of the clinical signs and histological lesions observed in dourine affected horses. In chapter IV, I attempted to reproduce the sexual transmission of T. equiperdum in mice. In chapter I, I focused on neurological signs of dourine, which observed in late to terminal stage of infection. Previous studies suggested that the neurological signs were probably attributed to the peripheral neuritis, however, the precise pathogenesis of the neuritis remains unclear. In this chapter, I identified the types of inflammatory cells infiltrating systemic peripheral neuritis observed in 4 dourine affected horses by immunohistochemistry, and compared those immunohistochemical natures between clinical stages of the affected horses (early, late, or terminal stage). As results, the infiltrating inflammatory cells were T lymphocytes, B lymphocytes, and macrophages, regardless of the clinical stage. Among T lymphocytes, CD8+ T lymphocytes were more predominant than CD4+ T lymphocytes. In macrophages, M2 macrophages were more predominant subtype than M1 macrophages. Those results indicated that the neuritis have natures of chronic inflammation. Also, those features were identical in all affected horses classified into early, late, or terminal stage. Therefore, while the neurological signs of dourine are clinically recognized in the late or terminal stage, peripheral neuritis may have already occurred in the acute stage of infection.\nIn chapter II, I have attempted to establish a mouse infection model that reproduces clinical signs and lesions including peripheral neuritis observed in dourine affected horses. Since mice are not susceptible to almost all T. equiperdum strains, mouse infection model of dourine has not been established. I infected female mice with T. equiperdum IVM-t2 strain, which is a newly isolated from dourine affected stallion in Mongolia, by intraperitoneal administration, and examined systemic organs of infected mice histopathologically. As results, infected mice developed periodic parasitemia during the experimental period (60 days). In those infected mice, peripheral neuritis similar to that found in affected horses were not observed. However, vaginitis and dermatitis with histological features similar to those found in affected horses were observed. Based on those findings, female mice infected with T. equiperdum IVMt2 strain may be a valuable experimental model for future pathological and parasitological research.\nIn Chapter III, I focused on male genital lesions in mice infected with T. equiperdum IVM-t2 strain intraperitoneally, and examined the reproductive organs of infected male mice histopathologically. Also, since anemia is one of the characteristic clinical signs of dourine, I also examined the hematocrit value of infected mice. As results, infected mice were persistently anemic throughout the experimental period (38 days). Histopathologically,  epididymitis with histological features similar to those in dourine affected stallions were observed in infected mice. Many trypanosomes were detected in the epididymal interstitium, and few were detected within the lumen of epididymal ducts. A large number of M1 and M2 macrophages infiltrated into the interstitium, and positive reactions for TNF-α, which is cytokine from M1 macrophages, was detected multifocally by immunofluorescence in those foci. Also, the apoptotic epithelial cells were increased in number. The aggregation of apoptotic epithelial cells was frequently associated with the loss of stainability for ZO-1, a major protein that forms tight junctions between epididymal epithelial cells. Also, the formation of sperm granuloma was observed in some infected mice. Trypanosomes in the epididymal interstitium is needed to invade the lumen for sexual transmission. The present results suggest that trypanosomes in the interstitium induce the infiltration of macrophages that secrete TNF-α, and may impair the tight\n junctions of epididymal ducts by using the function of TNF-α, which induce apoptosis.\n In chapter IV, to reproduce the sexual transmission of T. equiperdum between equids, I\n attempted sexual transmission of trypanosomes from male mice to female mice. Unfortunately, sexual transmission of the parasite between mice was not established. Thus, at this time, intraperitoneal administration is the most effective method to infect mice with T. equiperdum.\nIn conclusion, the present study revealed the part of the pathogenesis of peripheral neuritis observed in dourine affected horses by immunohistochemical investigations of spontaneous cases. Also, we established a mouse infection model that can reproduce some of the clinical signs and histological lesions observed in dourine affected horses. Additionally, histopathological examinations of epididymitis in infected male mice revealed new insights of the parasitic and transmission strategies of T. equiperdum.","subitem_description_language":"en","subitem_description_type":"Abstract"}]},"item_3_description_8":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"博士学位論文\n大学院畜産学研究科 獣医学専攻\nDoctoral Program of Veterinary Science","subitem_description_language":"ja","subitem_description_type":"Other"}]},"item_3_dissertation_number_13":{"attribute_name":"学位授与番号","attribute_value_mlt":[{"subitem_dissertationnumber":"甲第127号"}]},"item_3_publisher_5":{"attribute_name":"公開者","attribute_value_mlt":[{"subitem_publisher":"帯広畜産大学","subitem_publisher_language":"ja"}]},"item_3_rights_14":{"attribute_name":"権利","attribute_value_mlt":[{"subitem_rights":"田中　佑典","subitem_rights_language":"ja"}]},"item_3_subject_20":{"attribute_name":"日本十進分類法","attribute_value_mlt":[{"subitem_subject":"649","subitem_subject_scheme":"NDC"}]},"item_3_version_type_19":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_abf2"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"田中, 佑典","creatorNameLang":"ja"}],"nameIdentifiers":[{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2023-04-24"}],"displaytype":"detail","filename":"Tanaka.pdf","filesize":[{"value":"49.3 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"全文　Full text","objectType":"fulltext","url":"https://obihiro.repo.nii.ac.jp/record/4881/files/Tanaka.pdf"},"version_id":"0b5b8e3a-42ae-4500-8bd4-1f015546fc64"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2023-04-24"}],"displaytype":"detail","filename":"Abstract(Tanaka).pdf","filesize":[{"value":"155.1 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"全文の要旨　Abstract","url":"https://obihiro.repo.nii.ac.jp/record/4881/files/Abstract(Tanaka).pdf"},"version_id":"ec467036-3b33-48fe-bc24-254dbee67728"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2023-04-24"}],"displaytype":"detail","filename":"Evaluation(Tanaka).pdf","filesize":[{"value":"190.7 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"審査の要旨　Evaluation","url":"https://obihiro.repo.nii.ac.jp/record/4881/files/Evaluation(Tanaka).pdf"},"version_id":"c30e1cdc-f093-4c58-976e-c4a720ece902"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"jpn"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"doctoral thesis","resourceuri":"http://purl.org/coar/resource_type/c_db06"}]},"item_title":"Trypanosoma equiperdum ⾃然感染⾺および実験感染マウスに関する病理学的研究","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Trypanosoma equiperdum ⾃然感染⾺および実験感染マウスに関する病理学的研究","subitem_title_language":"ja"}]},"item_type_id":"3","owner":"12","path":["8"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2023-04-24"},"publish_date":"2023-04-24","publish_status":"0","recid":"4881","relation_version_is_last":true,"title":["Trypanosoma equiperdum ⾃然感染⾺および実験感染マウスに関する病理学的研究"],"weko_creator_id":"12","weko_shared_id":-1},"updated":"2024-01-18T08:14:25.552531+00:00"}