{"created":"2023-07-27T06:55:04.990971+00:00","id":50751,"links":{},"metadata":{"_buckets":{"deposit":"eace7409-6377-4924-a412-53579844895c"},"_deposit":{"created_by":18,"id":"50751","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"50751"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00050751","sets":["2812:2813:2826"]},"author_link":["85518","40"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2009-03","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"4p.","bibliographicVolumeNumber":"2005-2007","bibliographic_titles":[{"bibliographic_title":"平成19(2007)年度 科学研究費補助金 基盤研究(B) 研究成果報告書"},{"bibliographic_title":"2007 Fiscal Year Final Research Report","bibliographic_titleLang":"en"}]}]},"item_9_creator_33":{"attribute_name":"著者別表示","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{}],"nameIdentifiers":[{},{}]}]},"item_9_description_21":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"近年、精神疾患に対する再生医療が望まれており、そのために神経変性および再生医療の効果判定指標を明らかにする必要がある。本研究では、まず偏側神経破壊パーキンソン病モデルラットを用い、発症過程にみられる脳内ドーパミン神経機能変化をPET製剤投与により解析した。線条体のD2レセプターおよびドーパミン動態は急性期から変化し、これらは行動薬理試験や免疫染色の結果とも相関しており、発症過程の先行指標になり得ると考えられた(Neurosci. Lett., 389: 30-34, 2005)。加えて、再生医療の効果判定を目的として、同パーキンソン病モデルラットの破壊側線条体に胎仔中脳を移植した移植モデルを作成し、神経機能回復過程における内因性因子の経時的変化を評価した。その結果、胎仔脳移植群では、発現が低下した転写制御因子FosとZif268の濃度が回復することが明らかとなった(Synapse, 62: 920-926, 2008)。\n一方、SPECTへの応用を計画し、我々が開発した新規放射性ヨウ素標識アミノ酸を用いて同様に評価した結果、特にドーパ脱炭酸酵素活性では急性期より低下する傾向が認められ、早期診断への応用が期待された。また、核医学画像診断薬は、速やかに尿中排泄されるものが望ましい。既に、上記標識アミノ酸の尿排泄に有機酸輸送系(OAT)など複数の輸送蛋白が関与していることを確認し(Nucl. Med. Biol., 30: 31-37, 2003)、腎尿細管輸送機構を明らかにした(Ann. Nucl. Med., 18: 227-234, 263-270, 2004)。今回、Fanconi症候群モデルマウスの腎尿細管輸送特性を解析し、アミノ酸再吸収機能の特異的評価法を確立した(Ann. Nucl. Med., 20: 175-181, 2006)。さらに、腎尿細管分泌に関与するOATの一過性阻害により、標的組織移行性を向上させ得ることを示した(Nucl. Med. Biol., 34: 1003-1008, 2007)。\n以上より、処置後早期より変化する神経機能を検出し得たことから、これらを先行指標としたパーキンソン病あるいは再生医療効果判定の早期画像診断の可能性が示唆された。","subitem_description_type":"Abstract"},{"subitem_description":"We studied the PET tracer distributions of ligands for dopamine D_1 receptors ([^<11>C]SCH23390) and D_2 receptors ([^<11>C]raclopride) and of the dopamine precursor analog ([^<18>F]FDOPA) after 6-hydroxydopamine (6-OHDA) lesions of the medial forebrain bundle in rats. The brains of 6-OHDA treated rats were analyzed by tissue dissection at 3 days (acute stage) or 3 weeks (chronic stage) postlesion. [^<11>C] Raclopride, but not [^<11>C]SCH23390, showed a higher accumulation in the striatum on the lesion side compared with that on the intact side both 3 days and 3 weeks postlesion. On the other hand, a lower accumulation of [^<18>F]FDOPA was found in the striatum on the lesion side 3 days postlesion, and both in the striatum and cerebral cortex on the lesion side 3 weeks postlesion. An increase in raclopride and a decrease in FDOPA uptake in the denervated striatum is evident even at 3 days following the 6-OHDA lesions when the degree of methamphetamine (MAP)-induced rotation is not esta blished. Therefore the combination of D_2 antagonist and FDOPA may provide a potentially useful method for assessing the effects of dopamine depletion in Parkinson's disease.\nIn addition, we examined the topological specificity of MAP-induced activation of the immediate-early gene proteins, Fos and Zif268, in the nigrostriatal system in a unilateral 6-OHDA rat model of Parkinson's disease with or without intrastriatal grafts of fetal ventral mesencephalon. The differential expression of Fos and Zif268 was observed among the three regions of the nigrostriatal system following MAP in the 6-OHDA rats. This may suggest that Fos and Zif268 therefore possess gene-specific and region-specific functions in the basal ganglia nuclei.\nFor SPECT application, radioiodinated derivatives of dopamine biosynthesis precursor, [^<123>I]I-IMT and [^<123>I]I-FTM, were evaluated as diagnosis agents for early detection of neurodegeneration. In the biodistribution study, I-IMT accumulation in the striatum on the lesion side 3 days postlesion increased, then decreased in 2 weeks postlesion, compared with the intact side. On the other hand, I-FTM showed a lower accumulation in the striatum on the lesion side compared with that on the intact side both 3 days and 2 weeks postlesion. I-FTM, with an affinity to the final enzyme of dopamine biosynthesis, was sensitive for detection of neurodegeneration in acute stage. Thus, both I-IMT and I-FTM may be new candidates of sensitive radiopharmaceuticals in detecting function of cerebral dopaminergic neuron.","subitem_description_type":"Abstract"}]},"item_9_description_22":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"研究課題/領域番号:17390329, 研究期間(年度):2005-2007","subitem_description_type":"Other"},{"subitem_description":"出典：「脳内神経変性疾患に対する再生医療効果判定を可能にする新規放射性診断薬の開発」研究成果報告書　課題番号17390329\n  (KAKEN：科学研究費助成事業データベース（国立情報学研究所）)\n　　　本文データは著者版報告書より作成","subitem_description_type":"Other"}]},"item_9_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.24517/00057059","subitem_identifier_reg_type":"JaLC"}]},"item_9_publisher_17":{"attribute_name":"公開者","attribute_value_mlt":[{"subitem_publisher":"金沢大学医薬保健研究域保健学系"}]},"item_9_relation_28":{"attribute_name":"関連URI","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/search/?qm=30204663"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/search/?qm=30204663","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17390329/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17390329/","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-17390329/173903292007kenkyu_seika_hokoku_gaiyo/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-17390329/173903292007kenkyu_seika_hokoku_gaiyo/","subitem_relation_type_select":"URI"}}]},"item_9_version_type_25":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_ab4af688f83e57aa","subitem_version_type":"AM"}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2020-02-21"}],"displaytype":"detail","filename":"ME-PR-KAWAI-K-keken 2009-4p.pdf","filesize":[{"value":"228.4 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"ME-PR-KAWAI-K-keken 2009-4p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/50751/files/ME-PR-KAWAI-K-keken 2009-4p.pdf"},"version_id":"e7182f18-1955-41f7-9dce-b9f3f01e0ff2"}]},"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":"research report","resourceuri":"http://purl.org/coar/resource_type/c_18ws"}]},"item_title":"脳内神経変性疾患に対する再生医療効果判定を可能にする新規放射性診断薬の開発","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"脳内神経変性疾患に対する再生医療効果判定を可能にする新規放射性診断薬の開発"},{"subitem_title":"Development of novel radiopharmaceuticals for early stage diagnosis of cerebral neurodegeneration and functional recoverry after intrastriatal grafts","subitem_title_language":"en"}]},"item_type_id":"9","owner":"18","path":["2826"],"pubdate":{"attribute_name":"公開日","attribute_value":"2020-02-21"},"publish_date":"2020-02-21","publish_status":"0","recid":"50751","relation_version_is_last":true,"title":["脳内神経変性疾患に対する再生医療効果判定を可能にする新規放射性診断薬の開発"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2023-07-27T14:23:44.170512+00:00"}