明尼苏达大学Alfonso Araque小组近日取得一项新成果。经过不懈努力，他们揭示了不同的内源性大麻素特异性地向成年小鼠海马的星形胶质细胞或神经元发出信号。2025年12月30日，国际知名学术期刊《自然—神经科学》发表了这一成果。

在这里，小组发现2-AG选择性地向神经元发出信号，引起完全由神经元机制介导的抑制。相反，AEA向星形胶质细胞发出信号，诱导侧突触增强。

此外，AEA（而不是2-AG）和星形胶质细胞介导的信号传导是海马峰时间依赖性长期增强所必需的。因此，当2-AG选择性地向神经元发出信号时，AEA特异性地向星形胶质细胞发出信号，引起突触传递和可塑性的对比调节现象。这些结果揭示了不同的细胞类型特异性信号通路，包括独特的eCBs选择性地向神经元或星形胶质细胞发出信号。

据介绍，内源性大麻素（eCB）系统参与脑功能的许多过程。eCBs通过直接激活突触前CB1受体（CB1Rs）抑制突触传递，并通过激活星形细胞CB1Rs间接增强相邻突触。与其他神经递质系统相比，脑eCB系统涉及两种内源性配体，2-花生四烯醇甘油（2-AG）和阿南达胺（AEA），以及受体CB1R。这种特殊性的意义尚不清楚。

附：英文原文

Title: Distinct endocannabinoids specifically signal to astrocytes or neurons in the adult mouse hippocampus

Author: Noriega-Prieto, Jose Antonio, Falcn-Moya, Rafael, Noeker, Jacob A., Cai, Ruyi, Fundazuri, Unai B., Eraso-Pichot, Abel, Cai, Shangxuan, Guttipatti, Pavan, Belisle, Lindsey, Rodrguez-Moreno, Antonio, van der Stelt, Mario, Li, Yulong, Cheer, Joseph F., Marsicano, Giovanni, Kofuji, Paulo, Araque, Alfonso

Issue&Volume: 2025-12-30

Abstract: The endocannabinoid (eCB) system is involved in many processes in brain function. eCBs depress synaptic transmission by directly activating presynaptic CB1 receptors (CB1Rs), and they indirectly potentiate adjacent synapses by activating astrocytic CB1Rs. In contrast to other neurotransmitter systems, the brain eCB system involves two endogenous ligands, 2-arachidonoylglycerol (2-AG) and anandamide (AEA), and the receptor CB1R. The meaning of this particularity remains unknown. Here we show that 2-AG selectively signals to neurons, eliciting the depression, which is mediated exclusively by neuronal mechanisms. By contrast, AEA signals to astrocytes, inducing lateral synaptic potentiation. Moreover, AEA, but not 2-AG, and astrocyte-mediated signaling are required for hippocampal spike-timing-dependent long-term potentiation. Hence, while 2-AG selectively signals to neurons, AEA specifically signals to astrocytes, evoking contrasting regulatory phenomena of synaptic transmission and plasticity. These results reveal distinct cell-type-specific signaling pathways that involve unique eCBs selectively signaling to either neurons or astrocytes.

DOI: 10.1038/s41593-025-02148-1

Source: https://www.nature.com/articles/s41593-025-02148-1