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Novel role of the nociceptin system as a regulator of glutamate transporter expression in developing astrocytes
Author(s) -
Meyer Logan C.,
Paisley Caitlin E.,
Mohamed Esraa,
Bigbee John W.,
Kordula Tomasz,
Richard Hope,
Lutfy Kabirullah,
SatoBigbee Carmen
Publication year - 2017
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.23210
Subject(s) - nociceptin receptor , biology , glutamate receptor , astrocyte , microbiology and biotechnology , neuroscience , downregulation and upregulation , metabotropic glutamate receptor 5 , receptor , central nervous system , metabotropic glutamate receptor , biochemistry , opioid peptide , opioid , gene
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.