Glucocorticoid regulation of GLT-1 glutamate transporter isoform expression in the rat hippocampus.
BACKGROUND
In the rat hippocampus, the predominate glutamate transporters are GLT-1 and its recently identified isoform, GLT-1b. Chronic restraint stress increases GLT-1b expression throughout the hippocampus while more selectively increasing GLT-1 expression in the CA3 region. These studies suggest that GLT-1b expression is regulated by stress levels of glucocorticoids (GCs) and GLT-1 expression is regulated by stress-induced increases in extracellular glutamate levels in the CA3 region.


METHODS
In order to differentiate between the actions of GCs and glutamate, we examined GLT-1 isoform expression in adrenalectomized (ADX) rats and rats exposed to stress levels of GCs.


RESULTS
ADX rats revealed no significant differences in GLT-1b mRNA or protein levels compared to sham-operated controls or ADX rats given GC replacement. However, rats exposed to stress levels of GCs exhibited increases in GLT-1b protein expression in the CA3 region and the dentate gyrus. GLT-1 mRNA expression was increased by ADX, increases that were inhibited by GC replacement. Similarly, stress levels of GCs increased GLT-1 protein expression throughout the hippocampus.


CONCLUSIONS
Taken together, these data indicate that GLT-1b protein expression is regulated by stress levels of GCs while the regulation of GLT-1 mRNA and protein expression provides another example of the biphasic actions of GCs in the central nervous system.
Autry
Anita E
AE
Department of Pharmacology, Physiology and Neuroscience, School of Medicine, University of South Carolina, Columbia, SC 29208, USA.
Grillo
Claudia A
CA
Piroli
Gerardo G
GG
Rothstein
Jeffrey D
JD
McEwen
Bruce S
BS
Reagan
Lawrence P
LP
D000315:Adrenalectomy; D000818:Animals; D027342:Excitatory Amino Acid Transporter 2 / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000097:blood; D006624:Hippocampus / Q000378:metabolism*; D006854:Hydrocortisone / Q000097:blood*; D008297:Male; D020033:Protein Isoforms / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000378:metabolism*
D027342:Excitatory Amino Acid Transporter 2; D005938:Glucocorticoids; D020033:Protein Isoforms; D012333:RNA, Messenger; D006854:Hydrocortisone