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Department of Chemitry

International Journal

Neuroscience Letters
년도 2025
학술지명 Neuroscience Letters
논문명 Subregion-specific suppression of dopamine D1 receptor expression prevents L-DOPA-induced dyskinesia in a mouse model of Parkinson’s disease
게재권/집
수록페이지
저자명 Keita Sugiyama, Mahomi Kuroiwa, Takahide Shuto, Sehyeon Hwang, Yong-Seok Oh, Akinori Nishi
Link 관련링크 https://doi.org/10.1016/j.neulet.2025.138273 9356회 연결
Abstract

L-DOPA-induced dyskinesia (LID) is a debilitating motor complication that develops following prolonged L-DOPA therapy in patients with Parkinson’s disease (PD). Aberrant activation of dopamine D1 receptor (DRD1) signaling in D1-type/direct pathway medium spiny neurons (MSNs) of the striatum plays a critical role in the pathophysiology of LID. We previously characterized DRD1 signaling in seven striatal subregions and found that upregulation of DRD1 signaling in the intermediate/caudal part (IC) is associated with LID in a mouse model of PD. Here, we investigated whether DRD1 expression in the IC plays a causal role in LID development. Using an adeno-associated virus (AAV) expressing a short hairpin RNA against Drd1 (AAV-shDrd1), we selectively knocked down DRD1 expression in the IC of male mice. In unilateral 6-hydroxydopamine-lesioned mice, DRD1 knockdown in the IC significantly attenuated LID after acute and chronic L-DOPA treatment. In contrast, knockdown in either the rostral or intermediate/rostral part, previously identified as the LID-unrelated subregion, did not affect LID. These findings highlight the essential role of DRD1 and its signaling in the IC in LID development, providing valuable insights for developing novel therapeutic approaches.