title: Glutamate excitotoxicity activates the MAPK/ERK signaling pathway and induces the survival of rat hippocampal neurons in vivo.
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.
authors.affiliation: 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.
authors.forename: Daniel
authors.initials: D
authors.lastname: Ortuño-Sahagún
authors.forename: Raúl Montes
authors.initials: RM
authors.lastname: González
authors.forename: Ester
authors.initials: E
authors.lastname: Verdaguer
authors.forename: Verónica Chaparro
authors.initials: VC
authors.lastname: Huerta
authors.forename: Blanca M
authors.initials: BM
authors.lastname: Torres-Mendoza
authors.forename: Lourdes
authors.initials: L
authors.lastname: Lemus
authors.forename: Martha Catalina
authors.initials: MC
authors.lastname: Rivera-Cervantes
authors.forename: A
authors.initials: A
authors.lastname: Camins
authors.forename: C Beas
authors.initials: CB
authors.lastname: Zárate
mesh_terms: D000200:Action Potentials; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002470:Cell Survival; D002478:Cells, Cultured; D018698:Glutamic Acid / Q000633:toxicity*; D020935:MAP Kinase Signaling System; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018698:Glutamic Acid