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1	Riluzole elevates GLT-1 activity and levels in striatal astrocytes Carbone, M., Duty, S., Rattray, Marcus January 2012 (has links) No / 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. 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

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Riluzole elevates GLT-1 activity and levels in striatal astrocytes