Ciliary neurotrophic factor protects striatal neurons against excitotoxicity by enhancing glial glutamate uptake.

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 under...

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Autores principales:	Corinne Beurrier, Mathilde Faideau, Khaled-Ezaheir Bennouar, Carole Escartin, Lydia Kerkerian-Le Goff, Gilles Bonvento, Paolo Gubellini
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/92ed0c11fe5141daa8a890d2e8315783
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spelling	oai:doaj.org-article:92ed0c11fe5141daa8a890d2e83157832021-11-25T06:26:58ZCiliary neurotrophic factor protects striatal neurons against excitotoxicity by enhancing glial glutamate uptake.1932-620310.1371/journal.pone.0008550https://doaj.org/article/92ed0c11fe5141daa8a890d2e83157832010-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20062544/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Ciliary 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 approximately 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 (approximately 40% vs. approximately 7%), confirming an enhanced resistance to excitotoxicity. The GT inhibitor DL-threo-beta-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 (gamma-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.Corinne BeurrierMathilde FaideauKhaled-Ezaheir BennouarCarole EscartinLydia Kerkerian-Le GoffGilles BonventoPaolo GubelliniPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 1, p e8550 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Corinne Beurrier Mathilde Faideau Khaled-Ezaheir Bennouar Carole Escartin Lydia Kerkerian-Le Goff Gilles Bonvento Paolo Gubellini Ciliary neurotrophic factor protects striatal neurons against excitotoxicity by enhancing glial glutamate uptake.
description	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 approximately 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 (approximately 40% vs. approximately 7%), confirming an enhanced resistance to excitotoxicity. The GT inhibitor DL-threo-beta-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 (gamma-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.
format	article
author	Corinne Beurrier Mathilde Faideau Khaled-Ezaheir Bennouar Carole Escartin Lydia Kerkerian-Le Goff Gilles Bonvento Paolo Gubellini
author_facet	Corinne Beurrier Mathilde Faideau Khaled-Ezaheir Bennouar Carole Escartin Lydia Kerkerian-Le Goff Gilles Bonvento Paolo Gubellini
author_sort	Corinne Beurrier
title	Ciliary neurotrophic factor protects striatal neurons against excitotoxicity by enhancing glial glutamate uptake.
title_short	Ciliary neurotrophic factor protects striatal neurons against excitotoxicity by enhancing glial glutamate uptake.
title_full	Ciliary neurotrophic factor protects striatal neurons against excitotoxicity by enhancing glial glutamate uptake.
title_fullStr	Ciliary neurotrophic factor protects striatal neurons against excitotoxicity by enhancing glial glutamate uptake.
title_full_unstemmed	Ciliary neurotrophic factor protects striatal neurons against excitotoxicity by enhancing glial glutamate uptake.
title_sort	ciliary neurotrophic factor protects striatal neurons against excitotoxicity by enhancing glial glutamate uptake.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/92ed0c11fe5141daa8a890d2e8315783
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Ciliary neurotrophic factor protects striatal neurons against excitotoxicity by enhancing glial glutamate uptake.

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