Riluzole elevates GLT-1 activity and levels in striatal astrocytes
Carbone, M. Duty, S. Rattray, Marcus
Carbone, M.
Duty, S.
Rattray, Marcus
Publication Date
2012
End of Embargo
Supervisor
Keywords
Animals, Astrocytes, Drug effects, Metabolism, Ceftriaxone, Pharmacology, Cells, Cultured, Excitatory amino acid transporter 2, Metabolism, Glutamic acid, Metabolism, Isoxazoles, Pharmacology, Mice, Neostriatum, Cytology, Neuroprotective agents, Pharmacology, Riluzole, Up-regulation, EAAT2, Citicholine, Parkinson's disease, REF 2014
Rights
Peer-Reviewed
Open Access status
closedAccess
Accepted for publication
Institution
Department
Awarded
Embargo end date
Collections
Additional title
Abstract
Drugs which upregulate astrocyte glutamate transport may be useful neuroprotective compounds by preventing excitotoxicity. We set up a new system to identify potential neuroprotective drugs which act through GLT-1. Primary mouse striatal astrocytes grown in the presence of the growth-factor supplement G5 express high levels of the functional glutamate transporter, GLT-1 (also known as EAAT2) as assessed by Western blotting and (3)H-glutamate uptake assay, and levels decline following growth factor withdrawal. The GLT-1 transcriptional enhancer dexamethasone (0.1 or 1 muM) was able to prevent loss of GLT-1 levels and activity following growth factor withdrawal. In contrast, ceftriaxone, a compound previously reported to enhance GLT-1 expression, failed to regulate GLT-1 in this system. The neuroprotective compound riluzole (100 muM) upregulated GLT-1 levels and activity, through a mechanism that was not dependent on blockade of voltage-sensitive ion channels, since zonasimide (1 mM) did not regulate GLT-1. Finally, CDP-choline (10 muM-1 mM), a compound which promotes association of GLT-1/EAAT2 with lipid rafts was unable to prevent GLT-1 loss under these conditions. This observation extends the known pharmacological actions of riluzole, and suggests that this compound may exert its neuroprotective effects through an astrocyte-dependent mechanism.
Version
No full-text in the repository
Citation
Carbone, M., Duty, S., Rattray, M. (2012) Riluzole elevates GLT-1 activity and levels in striatal astrocytes. Neurochemistry International, 60(1), 31-38.
Link to publisher’s version
Link to published version
Link to Version of Record
Type
Article