DOI
https://doi.org/10.25772/SFCG-MK34
Author ORCID Identifier
0000-0003-4790-7251
Defense Date
2017
Document Type
Thesis
Degree Name
Master of Science
Department
Biochemistry
First Advisor
Dr. Carmen Sato-Bigbee
Abstract
Our previous results showed that oligodendrocyte development is regulated by both nociceptin and its G-protein coupled receptor, the nociceptin/orphanin FQ receptor (NOPR). The present in vitro and in vivo findings show that nociceptin plays a crucial conserved role in both human and rodent brain astrocytes, regulating the levels of the glutamate/aspartate transporter GLAST/EAAT1. This nociceptin-mediated response takes place during a critical developmental window that coincides with astrocyte maturation and synapse formation. GLAST/EAAT1 upregulation by nociceptin is mediated by NOPR 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.
Rights
© Logan Claire Meyer
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
6-21-2017