Repository Community: null
http://hdl.handle.net/20.500.11750/1211
2024-03-29T13:21:26Z
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Slitrk3 및 Nlgn2 억제제를 포함하는 불안장애 예방 또는 치료용 약학적 조성물
http://hdl.handle.net/20.500.11750/46301
Title: Slitrk3 및 Nlgn2 억제제를 포함하는 불안장애 예방 또는 치료용 약학적 조성물
Author(s): 김동욱; 엄지원; 고재원
Abstract: 본 발명은 Slitrk3 및 Nlgn2를 표적하여 불안장애를 치료할 수 있는 기술에 관한 것으로, 보다 구체적으로는 Slitrk3 및 Nlgn2 억제제를 유효성분으로 포함하는 불안장애 예방 또는 치료용 약학적 조성물 및 상기 조성물을 포함하는 약학 제제에 관한 것이다. 본 발명에 따르면 전전두엽 신경회로의 구조 및 활성을 조절하는 억제성 시냅스의 특성을 선택적으로 제어함으로써 불안증상에 관여하는 신경회로에 대한 지식을 제공하며, 상기 Slitrk3 및 Nlgn2 유전자는 불안증세 및 행 동을 조절할 수 있는 신약 개발을 위한 치료표적으로써 유용하게 이용될 수 있을 것으로 기대된다.
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Intracellular signaling mechanisms that shape postsynaptic GABAergic synapses
http://hdl.handle.net/20.500.11750/46133
Title: Intracellular signaling mechanisms that shape postsynaptic GABAergic synapses
Author(s): Jung, Hyeji; Kim, Seungjoon; Ko, Jaewon; Um, Ji Won
Abstract: Postsynaptic GABAergic receptors interact with various membrane and intracellular proteins to mediate inhibitory synaptic transmission. They form structural and/or signaling synaptic protein complexes that perform a variety of postsynaptic functions. In particular, the key GABAergic synaptic scaffold, gephyrin, and its interacting partners govern downstream signaling pathways that are essential for GABAergic synapse development, transmission, and plasticity. In this review, we discuss recent researches on GABAergic synaptic signaling pathways. We also outline the main outstanding issues that need to be addressed in this field and highlight the association of dysregulated GABAergic synaptic signaling with the onset of various brain disorders. © 2023 Elsevier Ltd
2023-07-31T15:00:00Z
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LPS induces microglial activation and GABAergic synaptic deficits in the hippocampus accompanied by prolonged cognitive impairment
http://hdl.handle.net/20.500.11750/45876
Title: LPS induces microglial activation and GABAergic synaptic deficits in the hippocampus accompanied by prolonged cognitive impairment
Author(s): Jung, Hyeji; Lee, Dongsu; You, Heejung; Lee, Myungha; Kim, Hyeonho; Cheong, Eunji; Um, Ji Won
Abstract: Neuroinflammation impacts the brain and cognitive behavior through microglial activation. In this study, we determined the temporal sequence from microglial activation to synaptic dysfunction and cognitive behavior induced by neuroinflammation in mice. We found that LPS injection activated microglia within a short period, followed by impairments in GABAergic synapses, and that these events led to long-term cognitive impairment. We demonstrated that, 3days after LPS injection, microglia in the hippocampus were significantly activated due to the LPS-induced inflammation in association with alterations in cellular morphology, microglial density, and expression of phagocytic markers. GABAergic synaptic impairments were detected at 4-6days after LPS treatment, a time when microglia activity had returned to normal. Consequently, memory impairment persisted for 6days after injection of LPS. Our results suggest that neuroinflammation induces microglia activation, GABAergic synaptic deficits and prolonged memory impairment over a defined temporal sequence. Our observations provide insight into the temporal sequence of neuroinflammation-associated brain pathologies. Moreover, the specific loss of inhibitory synapses accompanying the impaired inhibitory synaptic transmission provides mechanistic insight that may explain the prolonged cognitive deficit observed in patients with neuroinflammation. Thus, this study provides essential clues regarding early intervention strategies against brain pathologies accompanying neuroinflammation. © 2023. The Author(s).
2023-03-31T15:00:00Z
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Differential Regional Vulnerability of the Brain to Mild Neuroinflammation Induced by Systemic LPS Treatment in Mice
http://hdl.handle.net/20.500.11750/17366
Title: Differential Regional Vulnerability of the Brain to Mild Neuroinflammation Induced by Systemic LPS Treatment in Mice
Author(s): Jung, Hyeji; Lee, Hyojeong; Kim, Dongwook; Cheong, Eunji; Hyun, Young-Min; Yu, Je-Wook; Um, Ji Won
Abstract: Background: Peripheral inflammation-triggered mild neuroinflammation impacts the brain and behavior through microglial activation. In this study, we performed an unbiased analysis of the vulnerability of different brain areas to neuroinflammation induced by systemic inflammation. Methods: We injected mice with a single low dose of LPS to induce mild inflammation and then analyzed microglial activation in 34 brain regions by immunohistochemical methods and whole-brain imaging using multi-slide scanning microscopy. We also conducted quantitative RT-PCR to measure the levels of inflammatory cytokines in selected brain regions of interest. Results: We found that microglia in different brain regions are differentially activated by mild, LPS-induced inflammation relative to the increase in microglia numbers or increased CD68 expression. The increased number of microglia induced by mild inflammation was not attributable to infiltration of peripheral immune cells. In addition, microglia residing in brain regions, in which a single lowdose injection of LPS produced microglial changes, preferentially generated pro-inflammatory cytokines. Conclusion: Our results suggest that mild neuroinflammation induces regionally different microglia activation, producing proinflammatory cytokines. Our observations provide insight into induction of possible region-specific neuroinflammation-associated brain pathologies through microglial activation. © 2022 Jung et al.
2022-04-30T15:00:00Z