马萨诸塞州总医院Michael A. Wheeler研究组报道了控制恐惧的神经免疫相互作用的迷幻控制。2025年4月23日，国际知名学术期刊《自然》发表了这一成果。

该团队将基因组和行为筛选相结合，表明杏仁核中的星形胶质细胞通过表皮生长因子受体（EGFR）限制应激诱导的恐惧行为。从机制上讲，杏仁核星形胶质细胞中的EGFR表达抑制应激诱导的促炎信号转导级联，该级联通过杏仁核中的孤儿核受体NR2F2促进神经元-胶质串扰和应激诱导的恐惧行为。反过来，EGFR信号的减少和恐惧行为与慢性应激期间脑膜单核细胞的募集有关。这组神经免疫相互作用可以通过迷幻化合物的施用进行治疗，这种化合物可以逆转脑膜中单核细胞的积累以及恐惧行为。结合临床样本的验证，这些数据表明，迷幻药可以以神经精神疾病和潜在的其他炎症性疾病相关的神经免疫相互作用为主题。

据介绍，神经免疫相互作用-免疫细胞和脑细胞之间传递的信号-调节组织生理学的许多方面，包括对心理压力的反应，这可能使个体易患神经精神疾病。然而，造血细胞和脑驻留细胞之间影响复杂行为的相互作用尚不清楚。

附：英文原文

Title: Psychedelic control of neuroimmune interactions governing fear

Author: Chung, Elizabeth N., Lee, Jinsu, Polonio, Carolina M., Choi, Joshua, Akl, Camilo Faust, Kilian, Michael, Wei, Wiebke M., Gunner, Georgia, Ye, Mingyu, Heo, Tae Hyun, Drake, Sienna S., Yang, Liu, dEca, Catarina R. G. L., Lee, Joon-Hyuk, Deng, Liwen, Farrenkopf, Daniel, Schle, Anton M., Lee, Hong-Gyun, Afolabi, Oreoluwa, Ghaznavi, Sharmin, Smirnakis, Stelios M., Chiu, Isaac M., Kuchroo, Vijay K., Quintana, Francisco J., Wheeler, Michael A.

Issue&Volume: 2025-04-23

Abstract: Neuroimmune interactions—signals transmitted between immune and brain cells—regulate many aspects of tissue physiology1, including responses to psychological stress2,3,4,5, which can predispose individuals to develop neuropsychiatric diseases6,7,8,9. 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.

DOI: 10.1038/s41586-025-08880-9

Source: https://www.nature.com/articles/s41586-025-08880-9