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Excitotoxic Death of Retinal Neurons In Vivo Occurs via a Non-Cell-Autonomous Mechanism
- Publication Year :
- 2009
- Publisher :
- Society for Neuroscience, 2009.
-
Abstract
- 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 thisin vivostudy, we show that NMDA induces profound nuclear factor κB (NF-κB) activation in Müller glia but not in retinal neurons. Intriguingly, NMDA-induced death of retinal neurons is effectively blocked by inhibitors of NF-κB activity. We demonstrate that tumor necrosis factor α (TNFα) protein produced in Müller glial cells via an NMDA-induced NF-κB-dependent pathway plays a crucial role in excitotoxic loss of retinal neurons. This cell loss occurs mainly through a TNFα-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.
- Subjects :
- N-Methylaspartate
Cell Survival
Excitotoxicity
Stimulation
Mice, Transgenic
AMPA receptor
Biology
medicine.disease_cause
chemistry.chemical_compound
Mice
medicine
Excitatory Amino Acid Agonists
Animals
Mice, Knockout
Cell Death
Tumor Necrosis Factor-alpha
General Neuroscience
Glutamate receptor
Retinal
Articles
Cell biology
Mice, Inbred C57BL
medicine.anatomical_structure
chemistry
nervous system
NMDA receptor
Tumor necrosis factor alpha
Neuroscience
Muller glia
Retinal Neurons
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....ca6ae9b8bd360404d5a9080af7ac0043