Mitochondrial dysfunction is associated with long-term cognitive impairment in an animal sepsis model.

Autor:	Manfredini A; Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil., Constantino L; Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil., Pinto MC; Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil., Michels M; Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil., Burger H; Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil., Kist LW; Genomics and Molecular Biology Laboratory, Faculty of Biosciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, Brazil.; Postgraduate Program in Medicine and Health Sciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, Brazil., Silva MC; Laboratory of Bioenergetics, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil., Gomes LM; Laboratory of Bioenergetics, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil., Dominguini D; Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil., Steckert A; Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil., Simioni C; Plant Cell Biology Laboratory, Department of Cell Biology, Embryology and Genetics, Federal University of Santa Catarina, Florianópolis, Brazil., Bogo M; Genomics and Molecular Biology Laboratory, Faculty of Biosciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, Brazil.; Postgraduate Program in Medicine and Health Sciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, Brazil., Streck E; Laboratory of Bioenergetics, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil., Barichello T; Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, U.S.A.; Center of Excellence on Mood Disorders, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, U.S.A.; Laboratory of Experimental Microbiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil., de Quevedo J; Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, U.S.A.; Center of Excellence on Mood Disorders, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, U.S.A.; Neuroscience Graduate Program, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, U.S.A.; Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil., Singer M; Bloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College London, London, United Kingdom., Ritter C; Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil., Dal-Pizzol F; Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil fdpizzol@gmail.com.
Jazyk:	angličtina
Zdroj:	Clinical science (London, England : 1979) [Clin Sci (Lond)] 2019 Sep 24; Vol. 133 (18), pp. 1993-2004. Date of Electronic Publication: 2019 Sep 24 (Print Publication: 2019).
DOI:	10.1042/CS20190351
Abstrakt:	Background: Several different mechanisms have been proposed to explain long-term cognitive impairment in sepsis survivors. The role of persisting mitochondrial dysfunction is not known. We thus sought to determine whether stimulation of mitochondrial dynamics improves mitochondrial function and long-term cognitive impairment in an experimental model of sepsis. Methods: Sepsis was induced in adult Wistar rats by cecal ligation and perforation (CLP). Animals received intracerebroventricular injections of either rosiglitazone (biogenesis activator), rilmenidine, rapamycin (autophagy activators), or n-saline (sham control) once a day on days 7-9 after the septic insult. Cognitive impairment was assessed by inhibitory avoidance and object recognition tests. Animals were killed 24 h, 3 and 10 days after sepsis with the hippocampus and prefrontal cortex removed to determine mitochondrial function . Results: Sepsis was associated with both acute (24 h) and late (10 days) brain mitochondrial dysfunction. Markers of mitochondrial biogenesis, autophagy and mitophagy were not up-regulated during these time points. Activation of biogenesis (rosiglitazone) or autophagy (rapamycin and rilmenidine) improved brain ATP levels and ex vivo oxygen consumption and the long-term cognitive impairment observed in sepsis survivors. Conclusion: Long-term impairment of brain function is temporally related to mitochondrial dysfunction. Activators of autophagy and mitochondrial biogenesis could rescue animals from cognitive impairment. (© 2019 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)
Databáze:	MEDLINE
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