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Updated: Aug 4, 2026
10:36
Modeling Neuronal Death and Degeneration in Mouse Primary Cerebellar Granule Neurons
Published on: November 6, 2017
Excitotoxicity mediated by Ca2+-permeable GluR4-containing AMPA receptors involves the AP-1 transcription factor
A E Santos1, C B Duarte, M Iizuka
1Center for Neuroscience and Cell Biology, Department of Zoology, University of Coimbra, 3004-517 Coimbra, Portugal.
Cell Death and Differentiation
|November 12, 2005
Summary
Overactivation of GluR4-containing AMPA receptors triggers excitotoxicity. This cell death pathway involves the transcription factor activator protein-1 (AP-1).
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Cells expressing GluR4-containing AMPA receptors are vulnerable to excitotoxicity.
- The specific signaling pathways driving this excitotoxicity are not well understood.
Purpose of the Study:
- To investigate the downstream signaling pathways linked to excitotoxicity mediated by Ca2+-permeable GluR4-containing AMPA receptors.
Main Methods:
- Utilized a HEK 293 cell line stably expressing GluR4flip AMPA receptors (HEK-GluR4).
- Stimulated cells with glutamate, preventing receptor desensitization with cyclothiazide.
- Assessed cell viability and activator protein-1 (AP-1) DNA-binding activity.
- Examined the effect of inhibiting AP-1 activity using a c-Jun dominant-negative construct.
Main Results:
- Glutamate stimulation of GluR4-containing AMPA receptors reduced cell viability in a calcium-dependent manner.
- Excitotoxic stimulation elevated AP-1 DNA-binding activity.
- Inhibiting AP-1 activity via c-Jun dominant-negative expression protected cells from excitotoxic damage.
Conclusions:
- Overactivation of Ca2+-permeable GluR4-containing AMPA receptors initiates a cell death pathway.
- The transcription factor AP-1 plays a significant role in mediating this excitotoxicity.
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