title: Glutamate transporter expression and function in a striatal neuronal model of Huntington's disease.
abstract: Excitotoxicity may contribute to the pathogenesis of Huntington's disease. High affinity Na+ dependent glutamate transporters, residing in the plasma membrane, clear glutamate from the extracellular space and are the primary means of protection against excitotoxicity. Many reports suggest that Huntington's disease is associated with a decrease in the expression and function of glutamate transporters. We studied the expression and function of these transporters in a cellular model of Huntington's disease, STHdh(Q111/Q111) and STHdh(Q7/Q7) cells. We found that only GLT-1b and EAAC1 were expressed in these cell lines and only EAAC1 significantly contributed to the glutamate uptake. Surprisingly, there was an increase in Na+-dependent glutamate uptake in STHdh(Q111/Q111) cells accompanied by an increase in surface expression of EAAC1. We studied the influence of the Akt pathway on EAAC1 mediated uptake, since EAAC1 surface expression is influenced by Akt and previous studies have shown increased Akt expression in STHdh(Q111/Q111) cells. Glutamate uptake was inhibited by Akt pathway inhibitors in both the STHdh(Q7/Q7) and the STHdh(Q111/Q111) cell lines. We found no difference in Akt activation between the two cell lines under our conditions of culture. Therefore a difference in Akt activation does not seem to explain the increase in EAAC1 mediated uptake in the STHdh(Q111/Q111) cells.
authors.affiliation: Department of Neurology and the F.M. Kirby Neurobiology Center, Children's Hospital Boston, Boston, MA 02115, USA.
authors.forename: Geraldine T
authors.initials: GT
authors.lastname: Petr
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Bakradze
authors.forename: Natalie M
authors.initials: NM
authors.lastname: Frederick
authors.forename: Jianlin
authors.initials: J
authors.lastname: Wang
authors.forename: Wencke
authors.initials: W
authors.lastname: Armsen
authors.forename: Elias
authors.initials: E
authors.lastname: Aizenman
authors.forename: Paul A
authors.initials: PA
authors.lastname: Rosenberg
mesh_terms: D027322:Amino Acid Transport System X-AG / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
chemical_list: D027322:Amino Acid Transport System X-AG; D051057:Proto-Oncogene Proteins c-akt