https://scholar.dgist.ac.kr/handle/20.500.11750/1212 Tue, 27 Oct 2026 07:54:50 GMT 2026-10-27T07:54:50Z 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. Fri, 31 Jul 2026 15:00:00 GMT https://scholar.dgist.ac.kr/handle/20.500.11750/60961 2026-07-31T15:00:00Z https://scholar.dgist.ac.kr/handle/20.500.11750/60854 Title: Light-activated tetanus neurotoxin for conditional proteolysis and inducible synaptic inhibition in vivo Author(s): Roh, Heegwang; Kim, Dongwook; Kim, Byeongchan; Jeon, Younghyeon; Malhotra, Shreya; Kim, Hyeonho; Kim, Yeonghye; Jacko, Martin; Klein, Peter M.; Lin, Chang; Xu, Fei; Soltesz, Ivan; Um, Ji Won; Ting, Alice Y. Abstract: The light chain of tetanus neurotoxin (TeNT) is a metalloprotease that potently inhibits synaptic transmission by cleaving the endogenous vesicle fusion protein VAMP2, but its constitutive activity prevents spatiotemporal precision. To address this, we engineered light-activated TeNT (LATeNT) by inserting the light-sensitive LOV domain into an allosteric site and optimizing dynamic range via directed evolution. LATeNT's activity is undetectable in the dark, but the protease turns on after 10-20 min of weak blue-light exposure to potently inhibit synapses in vivo. Here we show that LATeNT works across multiple brain regions and at long-range axonal projections, with its effects reversible in 24 h. LATeNT enabled us to discover a hippocampal interneuron population that regulates anxiety-like behaviors and demonstrate the importance of postsynaptic endocannabinoid exocytosis for depolarization-induced suppression of inhibition in vivo. Beyond neuroscience, LATeNT regulated endogenous insulin secretion from pancreatic beta cells and converted drug exposure, elevated Ca2+ or receptor activation into transgene expression or reporter secretion in HEK293T cells. With a large dynamic range, high light sensitivity and sustained effect, LATeNT enables versatile, spatiotemporally resolved proteolysis across diverse biological systems. Fri, 31 Jul 2026 15:00:00 GMT https://scholar.dgist.ac.kr/handle/20.500.11750/60854 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. Fri, 31 Jul 2026 15:00:00 GMT https://scholar.dgist.ac.kr/handle/20.500.11750/60850 2026-07-31T15:00:00Z https://scholar.dgist.ac.kr/handle/20.500.11750/60598 Title: Loss of astrocytic Bmal1 promotes blood-brain barrier disruption and synaptic dysfunction during systemic inflammation Author(s): Lee, Changjun; Lee, Yelin; Jeong, Woo Chan; Hwang, Inhwa; Bae, Harin; Shim, Do-Wan; Jung, Hyeji; Um, Ji Won; Yu, Je-Wook Abstract: Circadian rhythm disruption has been associated with the exaggerated inflammatory responses in peripheral tissues; however, its impact on neuroinflammation and blood-brain barrier (BBB) integrity remains unclear. Here, we identify the astrocytic circadian clock as a key regulator of BBB homeostasis during systemic inflammation. In a mouse model, circadian rhythm disruption for three weeks markedly increased BBB permeability in male mice, as evidenced by Evans blue leakage and myeloid cell infiltration into the brain parenchyma following lipopolysaccharide (LPS) challenge. Transcriptomic analyses using public datasets revealed that astrocytes exhibit the highest expression of core circadian clock genes among brain cell types. Accordingly, we generated tamoxifen-inducible, astrocyte-specific Bmal1-knockout (KO) mice. Deletion of Bmal1 in astrocytes significantly enhanced BBB leakage, astrogliosis and pericyte loss after LPS administration. Mechanistically, Bmal1-deficient astrocytes produced elevated levels of the chemokine CXCL5, which promoted CXCR2-dependent neutrophil recruitment into the brain. Pharmacological blockade of CXCR2 with SB225002 restored pericyte coverage and attenuated BBB disruption in astrocytic Bmal1 KO mice. Functionally, these mice exhibited impaired excitatory synaptic transmission following systemic inflammation, suggesting that astrocytic Bmal1 loss compromises neurovascular and synaptic integrity. Taken together, our findings demonstrate that astrocytic Bmal1 maintains BBB integrity and synaptic stability under inflammatory stress. This work also highlights astrocyte-intrinsic circadian regulation as a critical mechanism linking chemokine production to neurovascular vulnerability. Thu, 30 Apr 2026 15:00:00 GMT https://scholar.dgist.ac.kr/handle/20.500.11750/60598 2026-04-30T15:00:00Z