https://scholar.dgist.ac.kr/handle/20.500.11750/301 2026-10-03T22:37:44Z 2026-10-03T22:37:44Z Jeong, Minseok Jang, Jin-Hyeok Oh, Seo-Jin Choi, Ji-Woong Oh, Yong-Seok https://scholar.dgist.ac.kr/handle/20.500.11750/60905 2026-09-29T06:10:15Z 2026-06-30T15:00:00Z

Title: Translational Profiling of Drd2-Expressing Populations Reveals Molecular Heterogeneity of Dentate Gyrus Mossy Cells along the Dorsoventral Axis Author(s): Jeong, Minseok; Jang, Jin-Hyeok; Oh, Seo-Jin; Choi, Ji-Woong; Oh, Yong-Seok Abstract: Hilar mossy cells (MCs) are crucial for integrating and propagating signals across the hippocampal dorsoventral axis, mediating cognitive and affective processing. While MCs exhibit profound dorsoventral differences in their projections, physiology, and behavioral roles, the molecular basis underlying this functional specialization remains largely unexplored. To address this gap, we used translating ribosome affinity purification (TRAP) in male mice to systematically compare the translatome of Drd2-expressing, MC-enriched populations along the dorsoventral axis. This analysis revealed distinct translational signatures with 1,442 genes enriched in dorsal and 1,337 genes in ventral Drd2-expressing, MC-enriched populations. Pathway analysis demonstrated significant functional segregation along the dorsoventral axis. The dorsal population is notably enriched for genes linked to neuronal connectivity and synaptic transmission, whereas the ventral counterpart shows enrichment in genes associated with energy metabolism and cellular maintenance. Specifically, we identified a subset of dorsal enriched genes, including neurotransmitter receptors, ion channels, and axon guidance regulators, contrasting with ventral enriched genes highly related to glucose/fatty acid metabolism, oxidative phosphorylation, and exocytosis. We further predicted distinct sets of upstream transcriptional regulators activated in each subpopulation, providing insights into the regulatory networks that may drive molecular divergence. Our findings provide a translatomic basis for the dorsoventral heterogeneity of Drd2-expressing neurons that include MCs, offering molecular signatures associated with their differential contributions to hippocampal function.

2026-06-30T15:00:00Z Oh, Seo-Jin Jang, Jin-Hyeok Roussarie, Jean-Pierre Jang, Kyung-un Jeong, Min-Seok Jo, Yeon Suk Shin, Chang Hun Choi, Hongsoo Lee, Kwang Yoon, Jong-Hyeok Oh, Yong-Seok https://scholar.dgist.ac.kr/handle/20.500.11750/59929 2026-09-02T01:10:14Z 2026-01-31T15:00:00Z

Title: Translational reprogramming of dentate gyrus peptidergic circuitry gates antidepressant efficacy Author(s): Oh, Seo-Jin; Jang, Jin-Hyeok; Roussarie, Jean-Pierre; Jang, Kyung-un; Jeong, Min-Seok; Jo, Yeon Suk; Shin, Chang Hun; Choi, Hongsoo; Lee, Kwang; Yoon, Jong-Hyeok; Oh, Yong-Seok 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.

2026-01-31T15:00:00Z Sugiyama, Keita Kuroiwa, Mahomi Shuto, Takahide Hwang, Sehyeon Oh, Yong-Seok Nishi, Akinori https://scholar.dgist.ac.kr/handle/20.500.11750/58491 2025-07-25T02:45:15Z 2025-06-30T15:00:00Z

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 Park, Jeongrak Kang, Seongtak Lee, Yaebin Choi, Ji-Woong Oh, Yong-Seok https://scholar.dgist.ac.kr/handle/20.500.11750/58442 2025-07-25T02:44:23Z 2023-12-31T15:00:00Z

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