Riluzole elevates GLT-1 activity and levels in striatal astrocytes, 2012, Carbone et al

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Riluzole elevates GLT-1 activity and levels in striatal astrocytes

Carbone, Marica; Duty, Susan; Rattray, Marcus

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 H-3-glutamate uptake assay, and levels decline following growth factor withdrawal. The GLT-1 transcriptional enhancer dexamethasone (0.1 or 1 mu M) 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 mu M) 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, COP-choline (10 mu M-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

Web | DOI | PMC | PDF | Neurochemistry International

 

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Seems potentially interesting, found while looking around astrocytes and glutamine. Also see this thread on glutamate and fatigue

 

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Also see

Glutamate Transporter EAAT2: A New Target For The Treatment Of Neurodegenerative Diseases, 2012, Lin et al

Spoiler: Authors

Lin, Chien-Liang Glenn; Kong, Qiongman; Cuny, Gregory D; Glicksman, Marcie A

Abstract
Glutamate is the primary excitatory amino acid neurotransmitter in the CNS. The concentration of glutamate in the synaptic cleft is tightly controlled by interplay between glutamate release and glutamate clearance. Abnormal glutamate release and/or dysfunction of glutamate clearance can cause overstimulation of glutamate receptors and result in neuronal injury known as excitotoxicity.

The glial glutamate transporter EAAT2 plays a major role in glutamate clearance. Dysfunction or reduced expression of EAAT2 has been documented in many neurodegenerative diseases. In addition, many studies in animal models of disease indicate that increased EAAT2 expression provides neuronal protection.

Here, we summarize these studies and suggest that EAAT2 is a potential target for the prevention of excitotoxicity. EAAT2 can be upregulated by transcriptional or translational activation. We discuss current progress in the search for EAAT2 activators, which is a promising direction for the treatment of neurodegenerative diseases.

Web | DOI | PMC | PDF | Future Medicinal Chemistry

 

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May not be a great fit as they talk about neuronal injury and excitotoxicity in neurodegenerative conditions, which isn’t quite what we’re looking for, but some if the ideas and mechanisms may be useful.

 

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Regardless of whether it could be a treatment for ME, it is another tool for probing the workings of the brain. If it does have the claimed effect on the brain, but doesn't affect ME symptoms, that at least reduces the research options to fund. Negative findings are useful.