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Glia. 2017 Dec;65(12):2003-2023. doi: 10.1002/glia.23210. Epub 2017 Sep 14.

Novel role of the nociceptin system as a regulator of glutamate transporter expression in developing astrocytes.

Author information

1
Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, School of Medicine, Richmond, Virginia.
2
Department of Anatomy and Neurobiology, Virginia Commonwealth University, School of Medicine, Richmond, Virginia.
3
Department of Pathology, Virginia Commonwealth University, School of Medicine, Richmond, Virginia.
4
Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, California.

Abstract

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.

KEYWORDS:

GLAST; astrocytes; brain development; glutamate transporters; nociceptin

PMID:
28906039
PMCID:
PMC5766282
DOI:
10.1002/glia.23210
[Indexed for MEDLINE]
Free PMC Article

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