한빛사
>
한빛사논문
한빛사논문
1
- 조회746
Nature, 23 April 2025 | https://doi.org/10.1038/s41586-025-08880-9
Psychedelic control of neuroimmune interactions governing fear
Elizabeth N. Chung 1,2,8, Jinsu Lee 1,2,8, Carolina M. Polonio 1,2, Joshua Choi 1,2, Camilo Faust Akl 1,2, Michael Kilian 1,2, Wiebke M. Weiß 1,2, Georgia Gunner 3, Mingyu Ye 4, Tae Hyun Heo 1,2, Sienna S. Drake 1,2, Liu Yang 1,2, Catarina R. G. L. d’Eca 1,2, Joon-Hyuk Lee 1,2, Liwen Deng 3, Daniel Farrenkopf 1,2, Anton M. Schüle 1,2, Hong-Gyun Lee 1,2, Oreoluwa Afolabi 1,2, Sharmin Ghaznavi 5,6, Stelios M. Smirnakis 4, Isaac M. Chiu 3, Vijay K. Kuchroo 1,2,7, Francisco J. Quintana 1,2,7 & Michael A. Wheeler 1,2,*
1The Gene Lay Institute of Immunology and Inflammation, Brigham and Women’s Hospital, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
2Ann Romney Center for Neurologic Diseases, Brigham and Women’s Hospital, Boston, MA, USA.
3Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
4Department of Neurology, Brigham and Women’s Hospital and Jamaica Plain Veterans Administration Hospital, Harvard Medical School, Boston, MA, USA.
5Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
6Center for the Neuroscience of Psychedelics, Massachusetts General Hospital, Boston, MA, USA.
7Broad Institute of MIT and Harvard, Cambridge, MA, USA.
8These authors contributed equally: Elizabeth N. Chung, Jinsu Lee
2Ann Romney Center for Neurologic Diseases, Brigham and Women’s Hospital, Boston, MA, USA.
3Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
4Department of Neurology, Brigham and Women’s Hospital and Jamaica Plain Veterans Administration Hospital, Harvard Medical School, Boston, MA, USA.
5Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
6Center for the Neuroscience of Psychedelics, Massachusetts General Hospital, Boston, MA, USA.
7Broad Institute of MIT and Harvard, Cambridge, MA, USA.
8These authors contributed equally: Elizabeth N. Chung, Jinsu Lee
*Corresponding author: correspondence to Michael A. Wheeler
Abstract
Neuroimmune interactions—signals transmitted between immune and brain cells—regulate many aspects of tissue physiology, including responses to psychological stress, which can predispose individuals to develop neuropsychiatric diseases. Still, the interactions between haematopoietic and brain-resident cells that influence complex behaviours are poorly understood. Here, we use a combination of genomic and behavioural screens to show that astrocytes in the amygdala limit stress-induced fear behaviour through epidermal growth factor receptor (EGFR). Mechanistically, EGFR expression in amygdala astrocytes inhibits a stress-induced, pro-inflammatory signal-transduction cascade that facilitates neuron–glial crosstalk and stress-induced fear behaviour through the orphan nuclear receptor NR2F2 in amygdala neurons. In turn, decreased EGFR signalling and fear behaviour are associated with the recruitment of meningeal monocytes during chronic stress. This set of neuroimmune interactions is therapeutically targetable through the administration of psychedelic compounds, which reversed the accumulation of monocytes in the brain meninges along with fear behaviour. Together with validation in clinical samples, these data suggest that psychedelics can be used to target neuroimmune interactions relevant to neuropsychiatric disorders and potentially other inflammatory diseases.
논문정보
- Research article
- 2025년 04월 (BRIC 등록일 2025-04-25)
- 국외 연구진
- 생명과학 > 면역학
댓글 작성 로그인
팝업 닫기관련 링크
연구자 키워드
소속기관 논문보기
관련분야 논문보기
해당논문 저자보기
