徳島大学 教育・研究者情報データベース(EDB)

1. 森垣 龍馬([徳島大学.大学院医歯薬学研究部.医学域.共同研究講座.先端脳機能研究開発]/[徳島大学.病院.診療科.脳·神経·精神科.脳神経外科])

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2. (英) Okita Shinya

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3. 後藤 惠

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(英) Dopamine-Induced Changes in G olf Protein Levels in Striatonigral and Striatopallidal Medium Spiny Neurons Underlie the Genesis of l-DOPA-Induced Dyskinesia in Parkinsonian Mice.

(英) 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 subunit (G olf), 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 G olf 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 G olf 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 G olf protein levels serve as a determinant of cAMP signal-dependent activity in striatal MSNs, we suggest that l-DOPA-induced changes in striatal G olf levels in the dopamine-depleted striatum could be a key event in generating LID.

1. (英) Article.ELocationID: 10.3389/fncel.2017.00026

2. (英) Article.PublicationTypeList.PublicationType: Journal Article

3. (英) KeywordList.Keyword: L-DOPA-induced dyskinesia

4. (英) KeywordList.Keyword: Parkinson disease

5. (英) KeywordList.Keyword: dopamine

6. (英) KeywordList.Keyword: olfactory type G-protein subunit

7. (英) KeywordList.Keyword: striatum