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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Meyer, LC; Paisley, CE; Mohamed, E; Bigbee, JW; Kordula, T; Richard, H; Lutfy, K; Sato-Bigbee, C

Published Date

  • December 2017

Published In

Volume / Issue

  • 65 / 12

Start / End Page

  • 2003 - 2023

PubMed ID

  • 28906039

Pubmed Central ID

  • PMC5766282

Electronic International Standard Serial Number (EISSN)

  • 1098-1136

International Standard Serial Number (ISSN)

  • 0894-1491

Digital Object Identifier (DOI)

  • 10.1002/glia.23210

Language

  • eng