アクセス数 : ?
ダウンロード数 : ?
ID 110886
タイトル別表記
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
著者
森垣, 龍馬 徳島大学大学院医科学教育部(医学専攻) 徳島大学 教育研究者総覧 KAKEN研究者をさがす
キーワード
olfactory type G-protein a subunit
dopamine
striatum
Parkinson’s disease
L-DOPA-induced dyskinesia
資料タイプ
学位論文
抄録
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.
掲載誌名
Frontiers in Cellular Neuroscience
ISSN
16625102
出版者
Frontiers Media S.A.
11
開始ページ
26
発行日
2017-02-10
備考
内容要旨・審査要旨・論文本文の公開
本論文は, 著者Ryoma Morigakiの学位論文として提出され, 学位審査・授与の対象となっている。
権利情報
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.
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第3097号
学位記番号
医第1341号
学位授与年月日
2017-07-27
学位名
博士(医学)
学位授与機関
徳島大学
部局
医学系
病院