https://scholar.dgist.ac.kr/handle/20.500.11750/299 2026-04-04T12:48:18Z https://scholar.dgist.ac.kr/handle/20.500.11750/59929 Title: Translational reprogramming of dentate gyrus peptidergic circuitry gates antidepressant efficacy Author(s): Seo-Jin Oh; Jin-jyeok Jang; Jean-Pierre Roussarie; Gyeong-un Jang; Min-seok Jeong; Yeon Suk Jo; Chang-Hoon Shin; Hongsoo Choi; Kwang Lee; Yoon, Jong-Hyeok; Yong-Seok Oh Abstract: Selective serotonin reuptake inhibitors (SSRIs) exhibit delayed therapeutic effects despite rapid serotonin elevation, suggesting their dependence on slow neuroplastic adaptations. Here, we demonstrate that antidepressant actions require cell type-specific translational regulation of the peptidergic signaling in the dentate gyrus (DG). Chronic, but not acute, treatment with an SSRI fluoxetine (FLX) selectively enhances translational activity in hilar mossy cells (MCs), with no detectable changes in neighboring granule cells (GCs). Combining Translating Ribosome Affinity Purification (TRAP) with RNA sequencing revealed distinct baseline translatomes between these two glutamatergic neurons and identified FLX-induced remodeling of peptidergic pathways in the DG. Crucially, we discovered MC-specific enrichment of the neuropeptide PACAP, which undergoes translation-dependent upregulation by chronic FLX treatment. This PACAP induction mediates neuroadaptive plasticity in PAC1 receptor-expressing GCs and drives behavioral responses prominently in female mice during prolonged FLX administration. Our findings establish cell type-specific translational reprogramming as a novel mechanistic framework for antidepressant action. https://scholar.dgist.ac.kr/handle/20.500.11750/59851 Title: 파킨슨 환자의 LID 발병 예측을 위한 정보제공방법 Author(s): 이예빈; 장진혁; 박정락; 오용석; 강성탁; 최지웅 Abstract: 본 발명은 본 발명은 토닉 도파민(tonic dopamine) 농도로부터 레보도파의 도파민 전환 속도를 확인하는 단계를 포함하는 파킨슨 환자의 레보도파 유발 운동이상증(L-DOPA-induced-dyskinesia, LID) 발병 예측을 위한 정보제공방법에 관한 것으로, 본 발명의 연구자들은 고급 FSCV(Fast Scan Cyclic Voltammetry) 기술을 활용하여 LID의 진행과정에서 레보도파 투여 후 도파민(DA) 동태를 성공적으로 측정하여 LID의 진행과정에서 레보도파의 약동학적 이상조절 현상 및 메커니즘을 확인하였으며, 이를 통한 파킨슨 환자의 LID 발병 예측을 위한 정보제공방법을 제공할 수 있다. https://scholar.dgist.ac.kr/handle/20.500.11750/58491 Title: Subregion-specific suppression of dopamine D1 receptor expression prevents L-DOPA-induced dyskinesia in a mouse model of Parkinson's disease Author(s): Sugiyama, Keita; Kuroiwa, Mahomi; Shuto, Takahide; Hwang, Sehyeon; Oh, Yong-Seok; Nishi, Akinori 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. © 2025 Elsevier B.V. 2025-06-30T15:00:00Z https://scholar.dgist.ac.kr/handle/20.500.11750/58442 Title: Continuous long-range measurement of tonic dopamine with advanced FSCV for pharmacodynamic analysis of levodopa-induced dyskinesia in Parkinson’s disease Author(s): Park, Jeongrak; Kang, Seongtak; Lee, Yaebin; Choi, Ji-Woong; Oh, Yong-Seok Abstract: Levodopa, a dopamine prodrug, alleviates the motor symptoms of Parkinson’s disease (PD), but its chronic use gives rise to levodopa-induced dyskinesia (LID). However, it remains unclear whether levodopa pharmacodynamics is altered during the progressive onset of LID. Using in vivo fast-scan cyclic voltammetry and second-derivative-based background drift removal, we continuously measured tonic dopamine levels using high temporal resolution recording over 1-h. Increases to tonic dopamine levels following acute levodopa administration were slow and marginal within the naïve PD model. However, these levels increased faster and higher in the LID model. Furthermore, we identified a strong positive correlation of dyskinetic behavior with the rate of dopamine increase, but much less with its cumulative level, at each time point. Here, we identified the altered signature of striatal DA dynamics underlying LID in PD using an advanced FSCV technique that demonstrates the long-range dynamics of tonic dopamine following drug administration. © 2024 Park, Kang, Lee, Choi and Oh. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). 2023-12-31T15:00:00Z