Dearth of glutamate transporters contributes to striatal excitotoxicity

Experimental Neurology
Tatiana BrustovetskyJanet M Dubinsky

Abstract

Since excitotoxicity is hypothesized to contribute to cell death in Huntington's disease (HD), we examined the susceptibility of striatal and hippocampal neurons to glutamate-induced cell death. Striatal cultures were more susceptible to glutamate-triggered toxicity than sister hippocampal cultures. Dose-response curves were equivalent when secondary toxicity was blocked with application of the NMDA receptor antagonist, MK801, or enhanced with the pan-specific glutamate transport blocker, TBOA, following excitotoxin removal. TBOA failed to alter the dose-response characteristics of striatal excitotoxicity, ruling out reverse operation of glutamate transporters. Striatal cultures expressed less EAAC1 and less membrane-associated EAAC1, GLT1, and GLAST than hippocampal cultures. Antisense down-regulation of EAAC1 increased the sensitivity of hippocampal cultures to glutamate, indicating that this transporter can act as an important neuroprotectant. Thus, the relative expression levels of glutamate transporters, even in parts of the brain where they are considered adequately expressed, appear to influence the sensitivities of different neuronal populations to excitotoxicity.

Citations

Aug 18, 2009·Journal of Molecular Neuroscience : MN·Veronica I BritoEva Küppers
Sep 9, 2006·BMC Neuroscience·Wenqi ZengJames F Gusella
Feb 12, 2014·Proceedings of the National Academy of Sciences of the United States of America·Barak RotblatPoul H Sorensen
Jan 18, 2012·Neurobiology of Disease·Matthew K BrittainNickolay Brustovetsky
Feb 1, 2011·Free Radical Biology & Medicine·Daniela SalveminiWilliam L Neumann
Jun 26, 2007·Journal of the Neurological Sciences·Josef VymazalJan Roth
May 23, 2007·Neurochemistry International·Amanda L Sheldon, Michael B Robinson
Apr 17, 2013·The European Journal of Neuroscience·Geraldine T PetrPaul A Rosenberg
Dec 28, 2011·Biochimica Et Biophysica Acta·Kali JanesDaniela Salvemini
Mar 17, 2007·Neuroscience·J LipskiD Donnelly
Jul 24, 2012·Neuropharmacology·Matthew K BrittainNickolay Brustovetsky
Apr 27, 2007·The Journal of Biological Chemistry·Elisa A WaxmanMichael B Robinson
Sep 2, 2017·Journal of Neuroscience Research·Etidal Al-SuwailemAfaf El-Ansary
Nov 20, 2008·Archives of Biochemistry and Biophysics·Daniela Salvemini

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