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P38 MAPK Inhibition Protects Against Glutamate Neurotoxicity and Modifies NMDA and AMPA Receptor Subunit Expression

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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.

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Acknowledgments

The authors wish to thank CONACYT for funding this work through grant No. 177594 to C.B.Z.

Author’s Contribution

Rivera-Cervantes Martha, Castañeda-Arellano Rolando, and Castro-Torres Ruben Darío: conception and design of the study, acquisition of data, or analysis and interpretation of data. Gudiño-Cabrera Graciela, Camins Antoni, Feria y Velasco Alfredo I, and Beas-Zárate Carlos: drafting the article or revising it critically for important intellectual content. Rivera-Cervantes Martha, and Beas-Zárate Carlos: review and final approval of the version to be submitted.

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Rivera-Cervantes, M.C., Castañeda-Arellano, R., Castro-Torres, R.D. et al. P38 MAPK Inhibition Protects Against Glutamate Neurotoxicity and Modifies NMDA and AMPA Receptor Subunit Expression. J Mol Neurosci 55, 596–608 (2015). https://doi.org/10.1007/s12031-014-0398-0

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