Riluzole elevates GLT-1 activity and levels in striatal astrocytes
Publication date
2012Keyword
AnimalsAstrocytes
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
Open Access status
closedAccess
Metadata
Show full item recordAbstract
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 repositoryCitation
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 Version of Record
https://doi.org/10.1016/j.neuint.2011.10.017Type
Articleae974a485f413a2113503eed53cd6c53
https://doi.org/10.1016/j.neuint.2011.10.017