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dc.contributor.authorCarbone, M.
dc.contributor.authorDuty, S.
dc.contributor.authorRattray, Marcus
dc.date.accessioned2014-04-25T12:29:12Z
dc.date.available2014-04-25T12:29:12Z
dc.date.issued2012
dc.identifier.citationCarbone, M., Duty, S., Rattray, M. (2012) Riluzole elevates GLT-1 activity and levels in striatal astrocytes. Neurochemistry International, 60(1), 31-38.
dc.identifier.urihttp://hdl.handle.net/10454/5907
dc.description.abstractDrugs 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.
dc.relation.isreferencedbyhttp://dx.doi.org/10.1016/j.neuint.2011.10.017
dc.subjectAnimals;
dc.subjectAstrocytes; Drug effects; Metabolism;
dc.subjectCeftriaxone; Pharmacology;
dc.subjectCells; Cultured;
dc.subjectExcitatory amino acid transporter 2; Metabolism;
dc.subjectGlutamic acid; Metabolism;
dc.subjectIsoxazoles; Pharmacology;
dc.subjectMice;
dc.subjectNeostriatum; Cytology;
dc.subjectNeuroprotective agents; Pharmacology;
dc.subjectRiluzole;
dc.subjectUp-regulation; EAAT2; Citicholine; Parkinson's disease;
dc.subjectREF 2014
dc.titleRiluzole elevates GLT-1 activity and levels in striatal astrocytes
dc.typeArticle


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