Dopamine-Induced Changes in Gαolf Protein Levels in Striatonigral and Striatopallidal Medium Spiny Neurons Underlie the Genesis of L-DOPA-Induced Dyskinesia in Parkinsonian Mice

• Material Type: 博士論文
• Title: Dopamine-Induced Changes in Gαolf Protein Levels in Striatonigral and Striatopallidal Medium Spiny Neurons Underlie the Genesis of L-DOPA-Induced Dyskinesia in Parkinsonian Mice
• Author/Editor: Morigaki, Ryoma; Okita, Shinya; Goto, Satoshi
• Author Heading: Morigaki, Ryoma; Okita, Shinya; Goto, Satoshi
• Publication, Distribution, etc.: Frontiers Media S.A.
• Publication Date: 2017-02-10
• Publication Date (W3CDTF): 2017-02-10
• Alternative Title: 線条体から黒質、淡蒼球に投射する中型有棘細胞のGαolfタンパクの発現はドパミン投与によって変化し、パーキンソン病モデルマウスにおけるL-ドーパ誘発性ジスキネジア発症に関与する; Striatal Gaolf Levels in L-DOPA-Induced Dyskinesia
• Periodical title: Frontiers in Cellular Neuroscience
• No. or year of volume/issue: 11
• Volume: 11
• Pages: 26-
• ISSN (Periodical Title): ISSN : 1662-5102
• Degree grantor/type: 徳島大学
• Date Granted: 2017-07-27
• Dissertation Number: 甲第3097号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: olfactory type G-protein a subunit; dopamine; striatum; Parkinson’s disease; L-DOPA-induced dyskinesia
• Target Audience: 一般
• Note (General): The dopamine precursor, L-3,4-dihydroxyphenylalanine (L-DOPA), exerts powerful therapeutic effects but eventually generates L-DOPA-induced dyskinesia (LID) in patients with Parkinson’s disease (PD). LID has a close link with deregulation of striatal dopamine/cAMP signaling, which is integrated by medium spiny neurons (MSNs). Olfactory type G-protein a subunit (Gaolf), a stimulatory GTP-binding protein encoded by the GNAL gene, is highly concentrated in the striatum, where it positively couples with dopamine D1 (D1R) receptor and adenosine A2A receptor (A2AR) to increase intracellular cAMP levels in MSNs. In the striatum, D1Rs are mainly expressed in the MSNs that form the striatonigral pathway, while D2Rs and A2ARs are expressed in the MSNs that form the striatopallidal pathway. Here, we examined the association between striatal Gaolf protein levels and the development of LID. We used a hemi-parkinsonian mouse model with nigrostriatal lesions induced by 6-hydroxydopamine (6-OHDA). Using quantitative immunohistochemistry (IHC) and a dual-antigen recognition in situ proximity ligation assay (PLA), we here found that in the dopamine-depleted striatum, there appeared increased and decreased levels of Gaolf protein in striatonigral and striatopallidal MSNs, respectively, after a daily pulsatile administration of L-DOPA. This leads to increased responsiveness to dopamine stimulation in both striatonigral and striatopallidal MSNs. Because Gaolf protein levels serve as a determinant of cAMP signal-dependent activity in striatal MSNs, we suggest that L-DOPA-induced changes in striatal Gaolf levels in the dopamine-depleted striatum could be a key event in generating LID.
• Format (IMT): application/pdf
• Access Restrictions: インターネット公開
• Rights (production): Copyright © 2017 Morigaki, Okita and Goto. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution and reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
• Related Material (DOI): 10.3389/fncel.2017.00026
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 徳島大学 : 徳島大学機関リポジトリ

Table of Contents

https://repo.lib.tokushima-u.ac.jp/files/public/11/110886/20171106121134596183/k3097_abstract_review.pdf fulltext

https://repo.lib.tokushima-u.ac.jp/files/public/11/110886/20171106160211547402/k3097_fulltext.pdf fulltext