Related Experiment Video
Updated: Apr 25, 2026
Using Enzyme-based Biosensors to Measure Tonic and Phasic Glutamate in Alzheimer's Mouse Models
Published on: May 3, 2017
P38 MAPK inhibition protects against glutamate neurotoxicity and modifies NMDA and AMPA receptor subunit expression
Martha Catalina Rivera-Cervantes1, Rolando Castañeda-Arellano, Ruben Darío Castro-Torres
1Laboratorio de Neurobiología Celular, Universidad de Guadalajara, Zapopan, Jal, Mexico.
Abstract:
NMDA and AMPA receptors are thought to be responsible for Ca(++) influx during glutamate-induced excitotoxicity and, therefore, hippocampal neuronal death. We assessed whether excitotoxicity induced by neonatal treatment with monosodium glutamate in rats at postnatal age of 1, 3, 5, and 7 modifies the hippocampal expression of the NMDAR subunit NR1 and the AMPAR subunits GluR1/GluR2 at postnatal days 8, 10, 12, and 14. We also assessed the involvement of MAPK signaling by using the p38 inhibitor SB203580. Our results showed that monosodium glutamate induces neuronal death and alters the expression of the subunits evaluated in the hippocampus at all ages studied, which could be prevented by SB203580 treatment.Furthermore, expression of the NRSF gene silencing factor also increased in response to excitotoxicity, suggesting a relationship in suppressing GluR2-expression, which was regulated by the p38-MAPK pathway inhibitor SB203580. This result suggests that selectively blocking the pro-death signaling pathway may reduce neuronal death in some neurodegenerative diseases in which these neurotoxic processes are present and produce major clinical benefits in the treatment of these pathologies.
Insights
Monosodium glutamate causes hippocampal neuronal death by altering NMDA and AMPA receptor subunit expression. Blocking the p38-MAPK pathway with SB203580 prevents this excitotoxicity, offering potential therapeutic benefits for neurodegenerative diseases.
Area of Science:
- Neuroscience
- Neuropharmacology
- Molecular Biology
Background:
- Glutamate excitotoxicity, mediated by NMDA and AMPA receptors, contributes to hippocampal neuronal death.
- Neonatal exposure to monosodium glutamate (MSG) is a model for studying excitotoxicity.
- MAPK signaling pathways, particularly p38-MAPK, are implicated in neuronal cell death.
Purpose of the Study:
- To investigate the effects of neonatal MSG-induced excitotoxicity on hippocampal NMDAR (NR1) and AMPAR (GluR1/GluR2) subunit expression in rats.
- To determine the role of the p38-MAPK signaling pathway in MSG-induced excitotoxicity and receptor subunit alterations.
- To evaluate the neuroprotective potential of the p38-MAPK inhibitor SB203580.
Main Methods:
- Neonatal rats were treated with MSG at different postnatal ages (1, 3, 5, 7 days).
- Hippocampal expression of NR1, GluR1, and GluR2 subunits was assessed at postnatal days 8, 10, 12, and 14.
- The p38-MAPK inhibitor SB203580 was administered to assess its effect on excitotoxicity and gene expression.
- Expression of the NRSF gene silencing factor was also analyzed.
Main Results:
- MSG treatment induced significant hippocampal neuronal death and altered NR1, GluR1, and GluR2 expression across all studied ages.
- SB203580 treatment effectively prevented MSG-induced neuronal death and normalized the expression of the evaluated receptor subunits.
- Excitotoxicity led to increased NRSF expression, suggesting a role in suppressing GluR2 expression, which was reversed by SB203580.
Conclusions:
- Neonatal MSG-induced excitotoxicity disrupts hippocampal NMDAR and AMPAR subunit expression in a time-dependent manner.
- The p38-MAPK pathway is critically involved in mediating MSG-induced excitotoxicity and associated changes in receptor expression.
- Selective inhibition of the p38-MAPK pathway represents a promising therapeutic strategy for neurodegenerative conditions characterized by excitotoxic neuronal death.
Related Concept Videos
01:30Ligand-Gated Ion Channel Receptor: Gating Mechanism
01:14Antiepileptic Drugs: Glutamate Antagonists
01:35Long-term Potentiation