Dopamine denervation of the prefrontal cortex increases expression of the astrocytic glutamate transporter GLT-1.

Vollbrecht PJ, Simmler LD, Blakely RD, Deutch AY
J Neurochem. 2014 130 (1): 109-14

PMID: 24611756 · PMCID: PMC4065617 · DOI:10.1111/jnc.12697

Both dopamine and glutamate are critically involved in cognitive processes such as working memory. Astrocytes, which express dopamine receptors, are essential elements in the termination of glutamatergic signaling: the astrocytic glutamate transporter GLT-1 is responsible for > 90% of cortical glutamate uptake. The effect of dopamine depletion on glutamate transporters in the prefrontal cortex (PFC) remains unknown. In an effort to determine if astrocytes are a locus of cortical dopamine-glutamate interactions, we examined the effects of chronic dopamine denervation on PFC protein and mRNA levels of glutamate transporters. PFC dopamine denervation elicited a marked increase in GLT-1 protein levels, but had no effect on levels of other glutamate transporters; high-affinity glutamate transport was positively correlated with the extent of dopamine depletion. GLT-1 gene expression was not altered. Our data suggest that dopamine depletion may lead to post-translational modifications that result in increased expression and activity of GLT-1 in PFC astrocytes. The glutamate transporter GLT-1 is expressed by astrocytes, which also express dopamine receptors. Regulation of prefrontal cortical (PFC) GLT-1 potentially offers a novel treatment approach to the cognitive deficits of schizophrenia. Partial PFC dopamine deafferentation increased membrane expression of GLT-1 protein and glutamate uptake, but did not alter levels of the other two neocortical glutamate transporters, GLAST and EAAC1.

© 2014 International Society for Neurochemistry.

MeSH Terms (11)

Animals Astrocytes Denervation Dopamine Excitatory Amino Acid Transporter 2 Gene Expression Regulation Male Prefrontal Cortex Protein Binding Rats Rats, Sprague-Dawley

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