title: Mitochondrial Dysfunction in Schizophrenia: Determination of Mitochondrial Respiratory Activity in a Two-Hit Mouse Model.
abstract: Schizophrenia is a chronic mental illness in which mitochondrial dysfunction has been suggested. Our laboratory recently developed a juvenile murine two-hit model (THM) of schizophrenia based on the combination of gestational inflammation, followed by juvenile restraint stress. We previously reported that relevant behaviors and neurochemical disturbances, including oxidative stress, were reversed by the antioxidant lipoic acid (LA), thereby pointing to the central role played by oxidative abnormalities and prompting us to investigate mitochondrial function. Mitochondrial activity was determined with the MitoXpress® commercial kit in two schizophrenia-relevant regions (prefrontal cortex (PFC) and striatum). Measurements were performed in state 3, with substrates for complex I- and complex II-induced respiratory activity (IRA). We observed an increase in complex I IRA in the PFC and striatum in both sexes but an increase in complex II activity only in males. LA treatment prevented this increase only in complex II IRA in males. Expression levels of the different respiratory chain complexes, as well as fission/fusion proteins and protein carbonylation, were unchanged. In conclusion, our juvenile schizophrenia THM shows an increase in mitochondrial activity reversed by LA, specifically in complex II IRA in males. Further investigations are required to determine the mechanisms of these modifications.
authors.affiliation: Department of Pharmacology and Physiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, 12e avenue Nord, Sherbrooke, QC, J1H 5N4, Canada.
authors.forename: Cécile
authors.initials: C
authors.lastname: Monpays
authors.affiliation: Department of Pharmacology and Physiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, 12e avenue Nord, Sherbrooke, QC, J1H 5N4, Canada.
authors.forename: Jessica
authors.initials: J
authors.lastname: Deslauriers
authors.affiliation: Department of Pharmacology and Physiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, 12e avenue Nord, Sherbrooke, QC, J1H 5N4, Canada.
authors.forename: Philippe
authors.initials: P
authors.lastname: Sarret
authors.affiliation: Department of Pharmacology and Physiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, 12e avenue Nord, Sherbrooke, QC, J1H 5N4, Canada. Sylvain.Grignon@usherbrooke.ca.|Department of Psychiatry, Centre Hospitalier Universitaire de Sherbrooke, 580 Bowen Sud, Sherbrooke, QC, J1G 2E8, Canada. Sylvain.Grignon@usherbrooke.ca.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Grignon
mesh_terms: D000818:Animals; D019069:Cell Respiration; D003342:Corpus Striatum / Q000378:metabolism; D042967:Electron Transport Complex I / Q000378:metabolism; D042963:Electron Transport Complex II / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress; D017397:Prefrontal Cortex / Q000378:metabolism; D050050:Protein Carbonylation; D012559:Schizophrenia / Q000378:metabolism*; D012737:Sex Factors; D008063:Thioctic Acid / Q000494:pharmacology
chemical_list: C478189:respiratory complex II; D008063:Thioctic Acid; D042963:Electron Transport Complex II; D042967:Electron Transport Complex I
keywords: Juvenile two-hit model; Lipoic acid; Mitochondrial respiration; Schizophrenia