Ciliary Neurotrophic Factor Protects Striatal Neurons against Excitotoxicity by Enhancing Glial Glutamate UptakeReportar como inadecuado




Ciliary Neurotrophic Factor Protects Striatal Neurons against Excitotoxicity by Enhancing Glial Glutamate Uptake - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Ciliary neurotrophic factor CNTF is a potent neuroprotective cytokine in different animal models of glutamate-induced excitotoxicity, although its action mechanisms are still poorly characterized. We tested the hypothesis that an increased function of glial glutamate transporters GTs could underlie CNTF-mediated neuroprotection. We show that neuronal loss induced by in vivo striatal injection of the excitotoxin quinolinic acid QA was significantly reduced by ∼75% in CNTF-treated animals. In striatal slices, acute QA application dramatically inhibited corticostriatal field potentials FPs, whose recovery was significantly higher in CNTF rats compared to controls ∼40% vs. ∼7%, confirming an enhanced resistance to excitotoxicity. The GT inhibitor dl-threo-β-benzyloxyaspartate greatly reduced FP recovery in CNTF rats, supporting the role of GT in CNTF-mediated neuroprotection. Whole-cell patch-clamp recordings from striatal medium spiny neurons showed no alteration of basic properties of striatal glutamatergic transmission in CNTF animals, but the increased effect of a low-affinity competitive glutamate receptor antagonist γ-d-glutamylglycine also suggested an enhanced GT function. These data strongly support our hypothesis that CNTF is neuroprotective via an increased function of glial GTs, and further confirms the therapeutic potential of CNTF for the clinical treatment of progressive neurodegenerative diseases involving glutamate overflow.



Autor: Corinne Beurrier, Mathilde Faideau, Khaled-Ezaheir Bennouar, Carole Escartin, Lydia Kerkerian-Le Goff, Gilles Bonvento, Paolo Gub

Fuente: http://plos.srce.hr/



DESCARGAR PDF




Documentos relacionados