https://scholar.dgist.ac.kr/handle/20.500.11750/1206 2026-10-27T07:04:29Z https://scholar.dgist.ac.kr/handle/20.500.11750/60961 Title: Somatostatin-induced modulation of microglial activity contributes to mitigating Alzheimer's disease pathology Author(s): Jung, Hyeji; Hyun, Gaeun; Kim, Seunghye; Jeon, Younghyeon; Han, Kyung Ah; Lee, Kea Joo; Ko, Jaewon; Um, Ji Won Abstract: Somatostatin (SST) is a neuropeptide widely expressed in the central nervous system, known to exert inhibitory effects through the activation of G protein-coupled somatostatin receptors (SSTRs). Although its synaptic and network-level functions have been implicated in various neurological disorders, the direct peptidergic actions of SST-particularly on microglia-remain poorly understood. Given that SST levels are reduced in Alzheimer's disease (AD) and that microglia predominantly express SSTR2, we hypothesized that SST modulates microglial function in both physiological and AD-related contexts. In this study, we demonstrate that SST treatment enhances phagocytic capacity and suppresses pro-inflammatory cytokine release in cultured microglia. Furthermore, SST overexpression in an AD mouse model reduced microglial density and amyloid-beta plaque burden and improved hippocampus-dependent cognitive performance, indicating a protective effect mediated through microglial modulation. Our findings reveal a previously unrecognized role of SST in regulating microglial behavior and highlight the therapeutic potential of targeting the SST-SSTR signaling axis in neuroinflammatory and neurodegenerative diseases. 2026-07-31T15:00:00Z https://scholar.dgist.ac.kr/handle/20.500.11750/60850 Title: Cytokine-mediated immune-to-brain signaling in neural circuit disorders Author(s): Lee, Yelin; Ko, Jaewon; Um, Ji Won Abstract: Neuroinflammation has emerged as a fundamental driver of neural circuit dysfunctions across a spectrum of neurodevelopmental and psychiatric disorders. Beyond classical neuroimmune pathologies, accumulating evidence indicates that systemic inflammatory states - including those elicited by infection, metabolic dysfunction, stress, or peripheral immune activation - induce profound and long-lasting alterations in brain development and function. Cytokines act as critical molecular mediators of this peripheral-to-central immune communication, precisely orchestrating microglial activation in a spatiotemporally restricted manner. Inflammasome-dependent signaling, particularly NLRP3 activation and subsequent cytokine release, has a central role in shaping microglial states during neuroinflammation. Here, we integrate current evidence linking systemic inflammation to microglial cytokine signaling programs and discuss how these cascades shape synaptic development, refinement, and circuit function. Although synapse pruning and cytokine-mediated microglial signaling jointly contribute to circuit remodeling, we highlight cytokine-driven microglial state amplification as a central mechanism linking systemic inflammation to neural circuit instability. We also highlight that specific cytokines can exert direct effects on neuronal populations - independent of microglial intermediates - to context-dependently modulate synaptic efficacy and circuit excitability. Finally, we evaluate the mechanisms linking systemic inflammation to brain dysfunction and highlight emerging translational opportunities, including the therapeutic repurposing of cytokine-targeting and immunomodulatory agents for neuropsychiatric interventions. 2026-07-31T15:00:00Z https://scholar.dgist.ac.kr/handle/20.500.11750/60358 Title: Juvenile-to-adult refinement of thalamic reticular circuits via LRRTM3 enables high-resolution sensory encoding Author(s): Lee, Dongsu; Han, Kyung Ah; Jeong, Hyeonyeong; Ha, Go Eun; Lee, Hyeongjin; Kim, Beom Soo; Park, Chanmi; Piao, Yao; Lee, Haeun; Kim, Joon; Yoon, Taek Han; Kim, Seungjoon; Kim, Byeongchan; Shin, Jungsu; Cho, Yujin; Kang, Sunghyun; Park, Han-Eol; Um, Ji Won; Sohn, Chang Ho; Huguenard, John R.; Ko, Jaewon; Cheong, Eunji Abstract: Sensory processing enables adaptive behavior by accurately encoding dynamic environmental stimuli. Within thalamocortical (TC) circuits, the thalamic reticular nucleus (TRN) functions as a key inhibitory gate that regulates cortical access to sensory input. While classical models posit that sensory circuits stabilize after early critical periods, we uncover a previously unrecognized phase of synaptic refinement in TRN circuitry extending from the juvenile period into adulthood. This late-stage remodeling is driven by a progressive reduction in corticothalamic (CT) excitatory input and is essential for enhancing sensory gain, response linearity, and stimulus discriminability. We identify LRRTM3, a TRN-enriched synaptic adhesion molecule, as a molecular gatekeeper of this process. TRN-specific deletion of LRRTM3 disrupts CT–TRN refinement, elevates TRN-mediated inhibition, and impairs fine tactile discrimination. These findings revise canonical views of sensory circuit maturation, revealing that LRRTM3-mediated juvenile-to-adult TRN plasticity is essential for the emergence of high-resolution sensory encoding in the adult brain. 2026-03-31T15:00:00Z https://scholar.dgist.ac.kr/handle/20.500.11750/60207 Title: A decade of progress in understanding LRRTM and Slitrk synaptic cell-adhesion molecules Author(s): Kim, Dongwook; Kim, Byeongchan; Um, Ji Won; Ko, Jaewon Abstract: For over a decade, synaptic cell-adhesion molecules (CAMs) have been recognized as fundamental determinants of neural circuit specificity and diversity. Among the CAMs, leucine-rich repeat (LRR)-containing transmembrane proteins have been established as crucial regulators of synaptic properties across diverse cell-types and brain regions. This minireview focuses on two families of LRR-containing CAMs: leucine-rich repeat transmembrane proteins (LRRTMs) and the Slit and Trk-like family (Slitrks). We provide a comprehensive synthesis of significant findings on LRRTMs and Slitrks since their initial characterization more than 15 years ago. Furthermore, we outline key unresolved questions to stimulate future studies on their functional mechanisms in neural circuit assembly and their pathophysiological roles in various neurological disorders. 2026-02-28T15:00:00Z