拉瓦尔大学Caroline Menard研究小组近日取得一项新成果。经过不懈努力，他们提出了星形胶质细胞大麻素受体1通过抑制应激诱导的血脑屏障改变来促进恢复力。相关论文于2025年2月27日发表于国际顶尖学术期刊《自然—神经科学》杂志上。

在这里，研究组报道了成年雄性小鼠的伏核（NAc）壳中星形细胞大麻素受体1 （CB1）的高表达，特别是在末端足鞘血管中，与慢性社会压力下的恢复能力有关。NAc壳星形胶质细胞中病毒介导的Cnr1的过表达导致雄性小鼠的基线抗焦虑作用，并抑制应激诱导的焦虑和抑郁样行为。它促进血管相关基因的表达，减少星形胶质细胞炎症反应和白细胞介素-6免疫挑战后的形态变化，这与应激易感性和情绪障碍有关。体育锻炼和抗抑郁治疗增加雄性小鼠血管周围区域星形细胞Cnr1的表达。在重度抑郁症男性供体的人体组织中，该课题组研究人员观察到NAc星形胶质细胞中CNR1的缺失。他们的发现表明星形细胞内源性大麻素系统通过调节血脑屏障在应激反应中起作用。

据悉，血脑屏障（BBB）的改变有助于应激易感性和抑郁行为的发展。相比之下，神经血管适应的压力恢复能力仍不清楚。

附：英文原文

Title: Astrocytic cannabinoid receptor 1 promotes resilience by dampening stress-induced blood–brain barrier alterations

Author: Dudek, Katarzyna A., Paton, Sam E. J., Binder, Luisa Bandeira, Collignon, Adeline, Dion-Albert, Laurence, Cadoret, Alice, Lebel, Manon, Lavoie, Olivier, Bouchard, Jonathan, Kaufmann, Fernanda Neutzling, Clavet-Fournier, Valerie, Manca, Claudia, Guzmn, Manuel, Campbell, Matthew, Turecki, Gustavo, Mechawar, Naguib, Flamand, Nicolas, Lavoie-Cardinal, Flavie, Silvestri, Cristoforo, Di Marzo, Vincenzo, Menard, Caroline

Issue&Volume: 2025-02-27

Abstract: Blood–brain barrier (BBB) alterations contribute to stress vulnerability and the development of depressive behaviors. In contrast, neurovascular adaptations underlying stress resilience remain unclear. Here we report that high expression of astrocytic cannabinoid receptor 1 (CB1) in the nucleus accumbens (NAc) shell, particularly in the end-feet ensheathing blood vessels, is associated with resilience during chronic social stress in adult male mice. Viral-mediated overexpression of Cnr1 in astrocytes of the NAc shell results in baseline anxiolytic effects and dampens stress-induced anxiety- and depression-like behaviors in male mice. It promotes the expression of vascular-related genes and reduces astrocyte inflammatory response and morphological changes following an immune challenge with the cytokine interleukin-6, linked to stress susceptibility and mood disorders. Physical exercise and antidepressant treatment increase the expression of astrocytic Cnr1 in the perivascular region in male mice. In human tissue from male donors with major depressive disorder, we observe loss of CNR1 in the NAc astrocytes. Our findings suggest a role for the astrocytic endocannabinoid system in stress responses via modulation of the BBB.

DOI: 10.1038/s41593-025-01891-9

Source: https://www.nature.com/articles/s41593-025-01891-9