QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, April 29, 2009, 29(17):5536-5545; doi:10.1523/JNEUROSCI.0831-09.2009

This Article Full Text Full Text (PDF) Supplemental Data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Related articles in J. Neurosci. Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lebrun-Julien, F. Articles by Di Polo, A. Search for Related Content PubMed PubMed Citation Articles by Lebrun-Julien, F. Articles by Di Polo, A. Pubmed/NCBI databases Compound via MeSH Substance via MeSH

 Previous Article  |  Next Article 

Cellular/Molecular
Excitotoxic Death of Retinal Neurons In Vivo Occurs via a Non-Cell-Autonomous Mechanism

Frédéric Lebrun-Julien,^1 * Laure Duplan,^1 * Vincent Pernet,¹ Ingrid Osswald,² Przemyslaw Sapieha,¹ Philippe Bourgeois,¹ Kathleen Dickson,³ Derek Bowie,² Philip A. Barker,^3 # and Adriana Di Polo^1 #

¹Department of Pathology and Cell Biology and Groupe de Recherche sur le Système Nerveux Central, Université de Montréal, Montreal, Quebec H3T 1J4, Canada, ²Department of Pharmacology and Therapeutics, and ³Centre for Neuronal Survival, Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada

Correspondence should be addressed to Dr. Adriana Di Polo, Department of Pathology and Cell Biology, Université de Montréal, 2900, Boulevard Edouard-Montpetit, Pavillon Roger-Gaudry, Room N-535, Montreal, QC H3T 1J4, Canada. Email: adriana.di.polo{at}umontreal.ca

The central hypothesis of excitotoxicity is that excessive stimulation of neuronal NMDA-sensitive glutamate receptors is harmful to neurons and contributes to a variety of neurological disorders. Glial cells have been proposed to participate in excitotoxic neuronal loss, but their precise role is defined poorly. In this in vivo study, we show that NMDA induces profound nuclear factor B (NF-B) activation in Müller glia but not in retinal neurons. Intriguingly, NMDA-induced death of retinal neurons is effectively blocked by inhibitors of NF-B activity. We demonstrate that tumor necrosis factor (TNF) protein produced in Müller glial cells via an NMDA-induced NF-B-dependent pathway plays a crucial role in excitotoxic loss of retinal neurons. This cell loss occurs mainly through a TNF-dependent increase in Ca²⁺-permeable AMPA receptors on susceptible neurons. Thus, our data reveal a novel non-cell-autonomous mechanism by which glial cells can profoundly exacerbate neuronal death following excitotoxic injury.

---

Received Feb. 18, 2009; accepted Feb. 25, 2009.

Correspondence should be addressed to Dr. Adriana Di Polo, Department of Pathology and Cell Biology, Université de Montréal, 2900, Boulevard Edouard-Montpetit, Pavillon Roger-Gaudry, Room N-535, Montreal, QC H3T 1J4, Canada. Email: adriana.di.polo{at}umontreal.ca

Related articles in J. Neurosci.:

This Week in The Journal

J. Neurosci. 2009 29: i. [Full Text]  

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help