한빛사논문
- 조회1,267
Young-Min Han1, Min Sun Kim1, Juyeong Jo1, Daiha Shin1, Seung-Hae Kwon1, Jong Bok SEO1, Dongmin Kang2, Byoung Dae Lee3, Hoon Ryu4, Eun Mi Hwang5, Jae-Min Kim6, Paresh D. Patel7, David M. Lyons8, Alan F. Schatzberg8, Song Her1
1 Seoul Centre, Korea Basic Science Institute, Seoul, South Korea 2 Department of Life Science, Ewha Womans University, Seoul, South Korea 3 Department of Physiology, School of Medicine, Kyung Hee University, Seoul, South Korea 4 Neuroscience Centre, Korea Institute of Science and Technology, Seoul, South Korea 5 Center for Functional Connectomics, Korea Institute of Science and Technology, Seoul, South Korea 6 Department of Psychiatry, Chonnam National University Medical School, Seoul, South Korea 7 Department of Psychiatry, Molecular and Behavioral Neuroscience Institute, University of Michigan Medical Centre, Ann Arbor, MI, USA 8 Departments of Psychiatry, Stanford University Medical Centre, Stanford, CA, USA
Correspondence to Song Her.
Abstract
The fine-tuning of neuroinflammation is crucial for brain homeostasis as well as its immune response. The transcription factor, nuclear factor-κ-B (NFκB) is a key inflammatory player that is antagonized via anti-inflammatory actions exerted by the glucocorticoid receptor (GR). However, technical limitations have restricted our understanding of how GR is involved in the dynamics of NFκB in vivo. In this study, we used an improved lentiviral-based reporter to elucidate the time course of NFκB and GR activities during behavioral changes from sickness to depression induced by a systemic lipopolysaccharide challenge. The trajectory of NFκB activity established a behavioral basis for the NFκB signal transition involved in three phases, sickness-early-phase, normal-middle-phase, and depressive-like-late-phase. The temporal shift in brain GR activity was differentially involved in the transition of NFκB signals during the normal and depressive-like phases. The middle-phase GR effectively inhibited NFκB in a glucocorticoid-dependent manner, but the late-phase GR had no inhibitory action. Furthermore, we revealed the cryptic role of basal GR activity in the early NFκB signal transition, as evidenced by the fact that blocking GR activity with RU486 led to early depressive-like episodes through the emergence of the brain NFκB activity. These results highlight the inhibitory action of GR on NFκB by the basal and activated hypothalamic-pituitary-adrenal (HPA)-axis during body-to-brain inflammatory spread, providing clues about molecular mechanisms underlying systemic inflammation caused by such as COVID-19 infection, leading to depression.
논문정보
- Research article
- 2021년 01월 (BRIC 등록일 2021-01-28)
- 국내(교신)+국외 연구진
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