https://scholar.dgist.ac.kr/handle/20.500.11750/10201 Sat, 04 Apr 2026 14:13:37 GMT 2026-04-04T14:13:37Z 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/20.500.11750/59929 https://scholar.dgist.ac.kr/handle/20.500.11750/9995 Title: Hippocampal mossy cell involvement in behavioral and neurogenic responses to chronic antidepressant treatment Author(s): Oh, Seo-Jin; Cheng, Jia; Jang, Jin-Hyeok; Arace, Jeffrey; Jeong, Minseok; Shin, Chang-Hoon; Park, Jeongrak; Jin, Junghee; Greengard, Paul; Oh, Yong-Seok Abstract: Most antidepressants, including selective serotonin reuptake inhibitors (SSRIs), initiate their drug actions by rapid elevation of serotonin, but they take several weeks to achieve therapeutic onset. This therapeutic delay suggests slow adaptive changes in multiple neuronal subtypes and their neural circuits over prolonged periods of drug treatment. Mossy cells are excitatory neurons in the dentate hilus that regulate dentate gyrus activity and function. Here we show that neuronal activity of hippocampal mossy cells is enhanced by chronic, but not acute, SSRI administration. Behavioral and neurogenic effects of chronic treatment with the SSRI, fluoxetine, are abolished by mossy cell-specific knockout of p11 or Smarca3 or by an inhibition of the p11/AnxA2/SMARCA3 heterohexamer, an SSRI-inducible protein complex. Furthermore, simple chemogenetic activation of mossy cells using Gq-DREADD is sufficient to elevate the proliferation and survival of the neural stem cells. Conversely, acute chemogenetic inhibition of mossy cells using Gi-DREADD impairs behavioral and neurogenic responses to chronic administration of SSRI. The present data establish that mossy cells play a crucial role in mediating the effects of chronic antidepressant medication. Our results indicate that compounds that target mossy cell activity would be attractive candidates for the development of new antidepressant medications. © 2019, Springer Nature Limited. Sun, 31 May 2020 15:00:00 GMT https://scholar.dgist.ac.kr/handle/20.500.11750/9995 2020-05-31T15:00:00Z https://scholar.dgist.ac.kr/handle/20.500.11750/9713 Title: Effects of Silibinin Against Prothrombin Kringle-2-Induced Neurotoxicity in the Nigrostriatal Dopaminergic System In Vivo Author(s): Leem, Eunju; Oh, Yong-Seok; Shin, Won-Ho; Jin, Byung Kwan; Jeong, Jae Yeong; Shin, Minsang; Kim, Dong Woon; Jang, Jin-Hyeok; Kim, Hyung-Jun; Ha, Chang Man; Jung, Un Ju; Moon, Gyeong Joon; Kim, Sang Ryong Abstract: Parkinson's disease (PD) and Alzheimer's disease exhibit common features of neurodegenerative diseases and can be caused by numerous factors. A common feature of these diseases is neurotoxic inflammation by activated microglia, indicating that regulation of microglial activation is a potential mechanism for preserving neurons in the adult brain. Recently, we reported that upregulation of prothrombin kringle-2 (pKr-2), one of the domains that make up prothrombin and which is cleaved and generated by active thrombin, induces nigral dopaminergic (DA) neuronal death through neurotoxic microglial activation in the adult brain. In this study, we show that silibinin, a flavonoid found in milk thistle, can suppress the production of inducible nitric oxide synthase and neurotoxic inflammatory cytokines, such as interleukin-1β and tumor necrosis factor-α, after pKr-2 treatment by downregulating the extracellular signal-regulated kinase signaling pathway in the mouse substantia nigra. Moreover, as demonstrated by immunohistochemical staining, measurements of the dopamine and metabolite levels, and open-field behavioral tests, silibinin treatment protected the nigrostriatal DA system resulting from the occurrence of pKr-2-triggered neurotoxic inflammation in vivo. Thus, we conclude that silibinin may be beneficial as a natural compound with anti-inflammatory effects against pKr-2-triggered neurotoxicity to protect the nigrostriatal DA pathway and its properties, and thus, may be applicable for PD therapy. © 2019, Mary Ann Liebert, Inc. Thu, 28 Feb 2019 15:00:00 GMT https://scholar.dgist.ac.kr/handle/20.500.11750/9713 2019-02-28T15:00:00Z https://scholar.dgist.ac.kr/handle/20.500.11750/9482 Title: Obligatory roles of dopamine D1 receptors in the dentate gyrus in antidepressant action of a selective serotonin reuptake inhibitor, fluoxetine Author(s): Shuto, Takahide; Kuroiwa, Mahomi; Sotogaku, Naoki; Kawahara, Yukie; Oh, Yong-Seok; Jang, Jin-Hyeok; Shin, Chang Hun; Ohnishi, Yoshinori; Hanada, Yuuki; Miyakawa, Tsuyoshi; Kim, Yong; Greengard, Paul; Nishi, Akinori Abstract: Depression is a leading cause of disability. Current pharmacological treatment of depression is insufficient, and development of improved treatments especially for treatment-resistant depression is desired. Understanding the neurobiology of antidepressant actions may lead to development of improved therapeutic approaches. Here, we demonstrate that dopamine D1 receptors in the dentate gyrus act as a pivotal mediator of antidepressant actions in mice. Chronic administration of a selective serotonin reuptake inhibitor (SSRI), fluoxetine, increases D1 receptor expression in mature granule cells in the dentate gyrus. The increased D1 receptor signaling, in turn, contributes to the actions of chronic fluoxetine treatment, such as suppression of acute stress-evoked serotonin release, stimulation of adult neurogenesis and behavioral improvement. Importantly, under severely stressed conditions, chronic administration of a D1 receptor agonist in conjunction with fluoxetine restores the efficacy of fluoxetine actions on D1 receptor expression and behavioral responses. Thus, our results suggest that stimulation of D1 receptors in the dentate gyrus is a potential adjunctive approach to improve therapeutic efficacy of SSRI antidepressants. © 2018, The Author(s). Sun, 31 May 2020 15:00:00 GMT https://scholar.dgist.ac.kr/handle/20.500.11750/9482 2020-05-31T15:00:00Z