近日，哈佛医学院Michael E. Greenberg及其小组的最新研究提出了星形胶质细胞糖皮质激素受体信号传导限制神经元可塑性。相关论文发表在2026年5月20日出版的《自然》杂志上。

在这里，课题组人员通过配对单细胞转录组和染色质可及性测序，研究了出生后发育中无主次初级视觉皮层的经验依赖性成熟。除了确定每种皮质细胞类型中出现的活性依赖基因程序外，该课题组人员还发现光照射通过细胞类型特异性的糖皮质激素受体（由Nr3c1编码）募集到染色质来驱动星形胶质细胞成熟。星形胶质细胞糖皮质激素受体信号传导激活了一个广泛的基因调控程序，该程序在人类大脑发育中部分保守，并促进了可能调节关键时期关闭的成熟过程。

总的来说，这些发现表明星形胶质细胞糖皮质激素受体信号传导限制了神经元的可塑性。糖皮质激素对星形胶质细胞成熟的调节也可能对整个大脑的早期生活压力产生影响，而这一过程的破坏可能会增加对神经精神疾病的易感性。

据悉，在出生后发育的关键时期，感觉体验改善了神经回路。虽然课题组人员知道神经元的活动能够协调构成这一过程的神经回路，但在动物成熟过程中，抑制发育可塑性的环境线索却不太清楚。

附：英文原文

Title: Astrocyte glucocorticoid receptor signalling restricts neuronal plasticity

Author: Gegenhuber, Bruno, Sonoda, Takuma, Traunmller, Lisa, Davis, Christopher P., Koren, Shon A., Griffith, Eric C., Chen, Chinfei, Greenberg, Michael E.

Issue&Volume: 2026-05-20

Abstract: Sensory experience refines neural circuits during critical periods of postnatal development1,2,3. Although neuronal activity is known to orchestrate the circuit wiring that underlies this process4,5, the environmental cues that restrain developmental plasticity as animals mature are less clear. Here we examine the experience-dependent maturation of the mouse primary visual cortex across postnatal development using paired single-cell transcriptomic and chromatin accessibility sequencing. In addition to identifying the activity-dependent gene programs that emerge within each cortical cell type, we find that light exposure drives astrocyte maturation through cell-type-specific recruitment of the glucocorticoid receptor (encoded by Nr3c1) to chromatin. Astrocyte glucocorticoid receptor signalling activates an extensive gene regulatory program that is partially conserved in human brain development and promotes maturation processes that may regulate critical period closure. Collectively, these findings reveal that astrocyte glucocorticoid receptor signalling restricts neuronal plasticity. Glucocorticoid regulation of astrocyte maturation may also contribute to the effects of early-life stress across the brain, and the disruption of this process may increase susceptibility to neuropsychiatric disease.

DOI: 10.1038/s41586-026-10512-9

Source: https://www.nature.com/articles/s41586-026-10512-9