Meinung Carl-Philipp, Boi Laura, Pandamooz Sareh, Mazaud David, Ghézali Grégory, Rouach Nathalie, Neumann Inga D
Department of Behavioral and Molecular Neurobiology, University of Regensburg, Regensburg, Germany.
Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Mol Psychiatry. 2025 Jun;30(6):2620-2634. doi: 10.1038/s41380-024-02870-5. Epub 2024 Dec 19.
Astrocytes are an indispensable part of signal processing within the mammalian brain. Thus, the mode of action of a neuropeptide such as oxytocin (OXT) can only be fully understood considering this integral part of the CNS. Here, we show that OXT regulates astrocytic gene expression, intracellular signaling and specific proteins both in vitro and in vivo. This translates into rapid regulation of astroglial structural and functional properties including cytoskeletal plasticity, coverage of synapses and gap-junction coupling. At the molecular level, we identify the previously undescribed Sp1-Gem signaling cascade as the key driver for these cell type-specific OXT effects. Finally at the behavioral level, we found in vivo that OXT requires astrocytes to exert its well described anxiolytic properties within the hypothalamic paraventricular nucleus. Thus, our study points to OXT receptor-expressing astrocytes as a critical component of the brain OXT system.
星形胶质细胞是哺乳动物大脑信号处理中不可或缺的一部分。因此，只有考虑到中枢神经系统的这一组成部分，才能充分理解诸如催产素（OXT）等神经肽的作用方式。在这里，我们表明OXT在体外和体内均调节星形胶质细胞的基因表达、细胞内信号传导和特定蛋白质。这转化为对星形胶质细胞结构和功能特性的快速调节，包括细胞骨架可塑性、突触覆盖和缝隙连接耦合。在分子水平上，我们确定了先前未描述的Sp1-Gem信号级联作为这些细胞类型特异性OXT效应的关键驱动因素。最后在行为水平上，我们在体内发现OXT需要星形胶质细胞来发挥其在下丘脑室旁核中众所周知的抗焦虑特性。因此，我们的研究指出表达OXT受体的星形胶质细胞是大脑OXT系统的关键组成部分。
