title: Chronic restraint stress up-regulates GLT-1 mRNA and protein expression in the rat hippocampus: reversal by tianeptine.
abstract: Excitatory amino acids play a key role in stress-induced remodeling of dendrites in the hippocampus as well as in suppression of neurogenesis in the dentate gyrus. The regulation of extracellular glutamate levels has been suggested as a potential mechanism through which repeated stress causes dendritic remodeling of CA3 pyramidal neurons. Accordingly, the current study examined the distribution and regulation of the glia glutamate transporter GLT-1 and the recently identified GLT isoform, GLT-1b, in the hippocampus of rats subjected to chronic restraint stress (CRS). We also examined the ability of the antidepressant tianeptine, which blocks CRS-induced dendritic remodeling, to modulate CRS-mediated changes in GLT-1 and GLT-1b expression. CRS increased GLT-1 mRNA expression in the dentate gyrus and CA3 region of Ammon's horn, increases that were inhibited by tianeptine. CRS more selectively increased GLT-1 protein levels in the subregion where dendritic remodeling is most prominent, namely the CA3 region, increases that were also inhibited by tianeptine administration. In contrast, GLT-1b mRNA expression was not modulated in the hippocampus in any of these groups, but CRS increased GLT-1b protein levels in all hippocampal subfields examined, increases that were unaffected by tianeptine treatment. These results point to the importance of understanding the mechanism for the differential and subregional regulation of GLT-1 isoforms in neuronal and glial compartments in the hippocampus as a basis for understanding the effects of chronic stress on structural plasticity as well as the neuroprotective properties of agents such as tianeptine.
authors.affiliation: Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA. lpreagan@gw.med.sc.edu
authors.forename: Lawrence P
authors.initials: LP
authors.lastname: Reagan
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Rosell
authors.forename: Gwendolyn E
authors.initials: GE
authors.lastname: Wood
authors.forename: Michael
authors.initials: M
authors.lastname: Spedding
authors.forename: Carmen
authors.initials: C
authors.lastname: Muñoz
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Rothstein
authors.forename: Bruce S
authors.initials: BS
authors.lastname: McEwen
mesh_terms: D000818:Animals; D002908:Chronic Disease; D027342:Excitatory Amino Acid Transporter 2 / Q000235:genetics*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000235:genetics*; D013841:Thiazepines / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D027342:Excitatory Amino Acid Transporter 2; D020033:Protein Isoforms; D012333:RNA, Messenger; D013841:Thiazepines; C050504:tianeptine