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Glutamate Excitotoxicity Activates the MAPK/ERK Signaling Pathway and Induces the Survival of Rat Hippocampal Neurons In Vivo |
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| Authors: | Daniel Ortuño-Sahagún Raúl Montes González Ester Verdaguer Verónica Chaparro Huerta Blanca M. Torres-Mendoza Lourdes Lemus Martha Catalina Rivera-Cervantes A. Camins C. Beas Zárate |
| Affiliation: | 1. Laboratorio de Desarrollo y Regeneración Neural, Instituto de Neurobiología, Departamento de Biología Celular y Molecular, CUCBA, Universidad de Guadalajara, Camino Ing. R. Padilla Sánchez, 2100, Las Agujas, Zapopan, 44600, Jalisco, Mexico 2. Laboratory of Cellular and Molecular Neurobiology, Division of Neuroscience, CIBO, IMSS, Guadalajara, Jalisco, Mexico 3. Department of Cellular Biology, Faculty of Biology, University of Barcelona, Nucli Universitari de Pedralbes, 08028, Barcelona, Spain 4. Centro de Investigación Biomédica de Occidente, IMSS, CUCS, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico 5. Depto. de Neonatología, Hosp. de Pediatría, CMNO, IMSS, Guadalajara, Jalisco, Mexico 6. Lab. of Neurobiol. Cell. and Molec., Neurobiol. Inst., Dept. of Cell and Molec. Biology, CUCBA, University of Guadalajara, Guadalajara, Jalisco, Mexico 7. Unitat de Farmacologia i Farmacognòsia Facultat de Farmàcia, Institut de Biomedicina (IBUB), Centros de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Universitat de Barcelona, Nucli Universitari de Pedralbes, 08028, Barcelona, Spain 8. Laboratory of Regeneration and Neuronal Development, Department of Cell and Molecular Biology, CUCBA, University of Guadalajara, Km. 15.5 Carr. Nogales, Zapopan, Jalisco, Mexico |
| Abstract: | Current knowledge concerning the molecular mechanisms of the cellular response to excitotoxic insults in neurodegenerative diseases is insufficient. Although glutamate (Glu) has been widely studied as the main excitatory neurotransmitter and principal excitotoxic agent, the neuroprotective response enacted by neurons is not yet completely understood. Some of the molecular participants have been revealed, but the signaling pathways involved in this protective response are just beginning to be identified. Here, we demonstrate in vivo that, in response to the cell damage and death induced by Glu excitotoxicity, neurons orchestrate a survival response through the extracellular signal-regulated kinase (ERK) signaling pathway by increasing ERK expression in the rat hippocampal (CA1) region, allowing increased neuronal survival. In addition, this protective response is specifically reversed by U0126, an ERK inhibitor, which promotes cell death only when it is administered together with Glu. Our findings demonstrate that the ERK signaling pathway has a neuroprotective role in the response to Glu-induced excitotoxicity in hippocampal neurons. Therefore, the ERK signaling pathway may be activated as a cellular response to excitotoxic injury to prevent damage and neural loss, representing a novel therapeutic target in the treatment of neurodegenerative diseases. |
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