Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, School of Medicine, Richmond, Virginia.
Department of Anatomy and Neurobiology, Virginia Commonwealth University, School of Medicine, Richmond, Virginia.
Glia. 2017 Dec;65(12):2003-2023. doi: 10.1002/glia.23210. Epub 2017 Sep 14.
Our previous results showed that oligodendrocyte development is regulated by both nociceptin and its G-protein coupled receptor, the nociceptin/orphanin FQ receptor (NOR). The present in vitro and in vivo findings show that nociceptin plays a crucial conserved role regulating the levels of the glutamate/aspartate transporter GLAST/EAAT1 in both human and rodent brain astrocytes. This nociceptin-mediated response takes place during a critical developmental window that coincides with the early stages of astrocyte maturation. GLAST/EAAT1 upregulation by nociceptin is mediated by NOR and the downstream participation of a complex signaling cascade that involves the interaction of several kinase systems, including PI-3K/AKT, mTOR, and JAK. Because GLAST is the main glutamate transporter during brain maturation, these novel findings suggest that nociceptin plays a crucial role in regulating the function of early astrocytes and their capacity to support glutamate homeostasis in the developing brain.
我们之前的研究结果表明，孤啡肽及其 G 蛋白偶联受体孤啡肽/孤啡肽受体（NOR）调节少突胶质细胞的发育。本研究的体外和体内结果表明，孤啡肽在调节人类和啮齿动物大脑星形胶质细胞中谷氨酸/天冬氨酸转运体 GLAST/EAAT1 的水平方面发挥着至关重要的保守作用。这种孤啡肽介导的反应发生在一个关键的发育窗口，与星形胶质细胞成熟的早期阶段相吻合。孤啡肽通过 NOR 介导 GLAST/EAAT1 的上调，并且涉及多个激酶系统的相互作用，包括 PI-3K/AKT、mTOR 和 JAK，从而参与下游的复杂信号级联反应。因为 GLAST 是大脑成熟过程中主要的谷氨酸转运体，这些新发现表明孤啡肽在调节早期星形胶质细胞的功能及其在发育中的大脑中维持谷氨酸稳态的能力方面发挥着关键作用。
