title: Chronic immobilization in the malpar1 knockout mice increases oxidative stress in the hippocampus.
abstract: The lysophosphatidic acid LPA₁ receptor has recently been involved in the adaptation of the hippocampus to chronic stress. The absence of LPA₁ receptor aggravates the chronic stress-induced impairment of both hippocampal neurogenesis and apoptosis that were accompanied with hippocampus-dependent memory deficits. Apoptotic death and neurogenesis in the hippocampus are regulated by oxidative stress. In the present work, we studied the involvement of LPA₁ receptor signaling pathway in the regulation of the hippocampal redox after chronic stress. To this end, we used malpar1 knockout (KO) and wild-type mice assigned to either chronic stress (21 days of restraint, 3 h/day) or control conditions. Lipid peroxidation, the activity of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPX), as well as mitochondrial function stimulation, monitored through the activity of cytochrome c oxidase (COX), were studied in the hippocampus. Our results showed that chronic immobilization stress enhanced lipid peroxidation as well as the activity of the antioxidant enzymes studied (CAT, SOD, and GPX). This effect was only observed in absence of LPA₁ receptor. Furthermore, only malpar1 KO mice submitted to chronic stress exhibited a severe downregulation of the COX activity, suggesting the presence of mitochondrial damage. Altogether, these results suggest that malpar1 KO mice display enhanced oxidative stress in the hippocampus after chronic stress. This may be involved in the hippocampal abnormalities observed in this genotype after chronic immobilization, including memory, neurogenesis, and apoptosis.
authors.affiliation: Departamento de Fisiología y Medicina Deportiva, Universidad de Málaga, Málaga, Spain.
authors.forename: María
authors.initials: M
authors.lastname: García-Fernández
authors.forename: Estela
authors.initials: E
authors.lastname: Castilla-Ortega
authors.forename: Carmen
authors.initials: C
authors.lastname: Pedraza
authors.forename: Eduardo
authors.initials: E
authors.lastname: Blanco
authors.forename: Isaac
authors.initials: I
authors.lastname: Hurtado-Guerrero
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Barbancho
authors.forename: Jerold
authors.initials: J
authors.lastname: Chun
authors.forename: Fernando
authors.initials: F
authors.lastname: Rodríguez-de-Fonseca
authors.forename: Guillermo
authors.initials: G
authors.lastname: Estivill-Torrús
authors.forename: Luis Javier
authors.initials: LJ
authors.lastname: Santín Núñez
mesh_terms: D000818:Animals; D002374:Catalase / Q000378:metabolism; D015536:Down-Regulation; D003576:Electron Transport Complex IV / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D049368:Receptors, Lysophosphatidic Acid / Q000235:genetics / Q000378:metabolism*; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D049368:Receptors, Lysophosphatidic Acid; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D003576:Electron Transport Complex IV