RapamycinFungusV1, Main, Exploration, bibRecord, 000278

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

Identifieur interne : 000278 ( Main/Exploration ); précédent : 000277; suivant : 000279

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

Auteurs : Andressa Manfredini [Brésil] ; Larissa Constantino [Brésil] ; Milton Castro Pinto [Brésil] ; Monique Michels [Brésil] ; Henrique Burger [Brésil] ; Luiza W. Kist [Brésil] ; Milena Carvalho Silva [Brésil] ; Lara Mezzari Gomes [Brésil] ; Diogo Dominguini [Brésil] ; Amanda Steckert [Brésil] ; Carmen Simioni [Brésil] ; Mauricio Bogo [Brésil] ; Emílio Streck [Brésil] ; Tatiana Barichello [États-Unis, Brésil] ; João De Quevedo [États-Unis, Brésil] ; Mervyn Singer [Royaume-Uni] ; Cristiane Ritter [Brésil] ; Felipe Dal-Pizzol [Oman]

Source :

Clinical science (London, England : 1979) [ 1470-8736 ] ; 2019.

RBID : pubmed:31527095

Descripteurs français

KwdFr :
- Analyse de survie (MeSH), Animaux (MeSH), Autophagie (effets des médicaments et des substances chimiques), Dynamique mitochondriale (effets des médicaments et des substances chimiques), Dysfonctionnement cognitif (anatomopathologie), Dysfonctionnement cognitif (complications), Encéphale (anatomopathologie), Encéphale (effets des médicaments et des substances chimiques), Mitochondries (anatomopathologie), Mitochondries (effets des médicaments et des substances chimiques), Mitochondries (métabolisme), Modèles animaux de maladie humaine (MeSH), Mâle (MeSH), Rat Wistar (MeSH), Rilménidine (pharmacologie), Rosiglitazone (pharmacologie), Régulation positive (effets des médicaments et des substances chimiques), Régulation positive (génétique), Sepsie (anatomopathologie), Sepsie (complications), Sirolimus (pharmacologie).
MESH :
- anatomopathologie : Dysfonctionnement cognitif, Encéphale, Mitochondries, Sepsie.
- effets des médicaments et des substances chimiques : Autophagie, Dynamique mitochondriale, Encéphale, Mitochondries, Régulation positive.
- génétique : Régulation positive.
- métabolisme : Mitochondries.
- pharmacologie : Dysfonctionnement cognitif, Rilménidine, Rosiglitazone, Sepsie, Sirolimus.
- Analyse de survie, Animaux, Modèles animaux de maladie humaine, Mâle, Rat Wistar.

English descriptors

KwdEn :
- Animals (MeSH), Autophagy (drug effects), Brain (drug effects), Brain (pathology), Cognitive Dysfunction (complications), Cognitive Dysfunction (pathology), Disease Models, Animal (MeSH), Male (MeSH), Mitochondria (drug effects), Mitochondria (metabolism), Mitochondria (pathology), Mitochondrial Dynamics (drug effects), Rats, Wistar (MeSH), Rilmenidine (pharmacology), Rosiglitazone (pharmacology), Sepsis (complications), Sepsis (pathology), Sirolimus (pharmacology), Survival Analysis (MeSH), Up-Regulation (drug effects), Up-Regulation (genetics).
MESH :
- chemical , pharmacology : Rilmenidine, Rosiglitazone, Sirolimus.
- complications : Cognitive Dysfunction, Sepsis.
- drug effects : Autophagy, Brain, Mitochondria, Mitochondrial Dynamics, Up-Regulation.
- genetics : Up-Regulation.
- metabolism : Mitochondria.
- pathology : Brain, Cognitive Dysfunction, Mitochondria, Sepsis.
- Animals, Disease Models, Animal, Male, Rats, Wistar, Survival Analysis.

Abstract

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.

DOI: 10.1042/CS20190351
PubMed: 31527095

Affiliations:

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Le document en format XML

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<sourceDesc><biblStruct><analytic><title xml:lang="en">Mitochondrial dysfunction is associated with long-term cognitive impairment in an animal sepsis model.</title>
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<author><name sortKey="Constantino, Larissa" sort="Constantino, Larissa" uniqKey="Constantino L" first="Larissa" last="Constantino">Larissa Constantino</name>
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<author><name sortKey="Pinto, Milton Castro" sort="Pinto, Milton Castro" uniqKey="Pinto M" first="Milton Castro" last="Pinto">Milton Castro Pinto</name>
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<author><name sortKey="Michels, Monique" sort="Michels, Monique" uniqKey="Michels M" first="Monique" last="Michels">Monique Michels</name>
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<author><name sortKey="Burger, Henrique" sort="Burger, Henrique" uniqKey="Burger H" first="Henrique" last="Burger">Henrique Burger</name>
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<author><name sortKey="Kist, Luiza W" sort="Kist, Luiza W" uniqKey="Kist L" first="Luiza W" last="Kist">Luiza W. Kist</name>
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<wicri:regionArea>Postgraduate Program in Medicine and Health Sciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS</wicri:regionArea>
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<author><name sortKey="Silva, Milena Carvalho" sort="Silva, Milena Carvalho" uniqKey="Silva M" first="Milena Carvalho" last="Silva">Milena Carvalho Silva</name>
<affiliation wicri:level="2"><nlm:affiliation>Laboratory of Bioenergetics, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil.</nlm:affiliation>
<country xml:lang="fr">Brésil</country>
<wicri:regionArea>Laboratory of Bioenergetics, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC</wicri:regionArea>
<placeName><region type="state">Santa Catarina</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Gomes, Lara Mezzari" sort="Gomes, Lara Mezzari" uniqKey="Gomes L" first="Lara Mezzari" last="Gomes">Lara Mezzari Gomes</name>
<affiliation wicri:level="2"><nlm:affiliation>Laboratory of Bioenergetics, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil.</nlm:affiliation>
<country xml:lang="fr">Brésil</country>
<wicri:regionArea>Laboratory of Bioenergetics, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC</wicri:regionArea>
<placeName><region type="state">Santa Catarina</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Dominguini, Diogo" sort="Dominguini, Diogo" uniqKey="Dominguini D" first="Diogo" last="Dominguini">Diogo Dominguini</name>
<affiliation wicri:level="2"><nlm:affiliation>Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil.</nlm:affiliation>
<country xml:lang="fr">Brésil</country>
<wicri:regionArea>Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC</wicri:regionArea>
<placeName><region type="state">Santa Catarina</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Steckert, Amanda" sort="Steckert, Amanda" uniqKey="Steckert A" first="Amanda" last="Steckert">Amanda Steckert</name>
<affiliation wicri:level="2"><nlm:affiliation>Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil.</nlm:affiliation>
<country xml:lang="fr">Brésil</country>
<wicri:regionArea>Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC</wicri:regionArea>
<placeName><region type="state">Santa Catarina</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Simioni, Carmen" sort="Simioni, Carmen" uniqKey="Simioni C" first="Carmen" last="Simioni">Carmen Simioni</name>
<affiliation wicri:level="1"><nlm:affiliation>Plant Cell Biology Laboratory, Department of Cell Biology, Embryology and Genetics, Federal University of Santa Catarina, Florianópolis, Brazil.</nlm:affiliation>
<country xml:lang="fr">Brésil</country>
<wicri:regionArea>Plant Cell Biology Laboratory, Department of Cell Biology, Embryology and Genetics, Federal University of Santa Catarina, Florianópolis</wicri:regionArea>
<wicri:noRegion>Florianópolis</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Bogo, Mauricio" sort="Bogo, Mauricio" uniqKey="Bogo M" first="Mauricio" last="Bogo">Mauricio Bogo</name>
<affiliation wicri:level="2"><nlm:affiliation>Genomics and Molecular Biology Laboratory, Faculty of Biosciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, Brazil.</nlm:affiliation>
<country xml:lang="fr">Brésil</country>
<wicri:regionArea>Genomics and Molecular Biology Laboratory, Faculty of Biosciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS</wicri:regionArea>
<placeName><region type="state">Rio Grande do Sul</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:affiliation>Postgraduate Program in Medicine and Health Sciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, Brazil.</nlm:affiliation>
<country xml:lang="fr">Brésil</country>
<wicri:regionArea>Postgraduate Program in Medicine and Health Sciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS</wicri:regionArea>
<placeName><region type="state">Rio Grande do Sul</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Streck, Emilio" sort="Streck, Emilio" uniqKey="Streck E" first="Emílio" last="Streck">Emílio Streck</name>
<affiliation wicri:level="2"><nlm:affiliation>Laboratory of Bioenergetics, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil.</nlm:affiliation>
<country xml:lang="fr">Brésil</country>
<wicri:regionArea>Laboratory of Bioenergetics, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC</wicri:regionArea>
<placeName><region type="state">Santa Catarina</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Barichello, Tatiana" sort="Barichello, Tatiana" uniqKey="Barichello T" first="Tatiana" last="Barichello">Tatiana Barichello</name>
<affiliation wicri:level="2"><nlm:affiliation>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.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX</wicri:regionArea>
<placeName><region type="state">Texas</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:affiliation>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.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>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</wicri:regionArea>
<placeName><region type="state">Texas</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:affiliation>Laboratory of Experimental Microbiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil.</nlm:affiliation>
<country xml:lang="fr">Brésil</country>
<wicri:regionArea>Laboratory of Experimental Microbiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC</wicri:regionArea>
<placeName><region type="state">Santa Catarina</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="De Quevedo, Joao" sort="De Quevedo, Joao" uniqKey="De Quevedo J" first="João" last="De Quevedo">João De Quevedo</name>
<affiliation wicri:level="2"><nlm:affiliation>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.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX</wicri:regionArea>
<placeName><region type="state">Texas</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:affiliation>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.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>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</wicri:regionArea>
<placeName><region type="state">Texas</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:affiliation>Neuroscience Graduate Program, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, U.S.A.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Neuroscience Graduate Program, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX</wicri:regionArea>
<placeName><region type="state">Texas</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:affiliation>Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil.</nlm:affiliation>
<country xml:lang="fr">Brésil</country>
<wicri:regionArea>Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC</wicri:regionArea>
<placeName><region type="state">Santa Catarina</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Singer, Mervyn" sort="Singer, Mervyn" uniqKey="Singer M" first="Mervyn" last="Singer">Mervyn Singer</name>
<affiliation wicri:level="4"><nlm:affiliation>Bloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College London, London, United Kingdom.</nlm:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Bloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College London, London</wicri:regionArea>
<placeName><settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
<orgName type="university">University College de Londres</orgName>
</affiliation>
</author>
<author><name sortKey="Ritter, Cristiane" sort="Ritter, Cristiane" uniqKey="Ritter C" first="Cristiane" last="Ritter">Cristiane Ritter</name>
<affiliation wicri:level="2"><nlm:affiliation>Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil.</nlm:affiliation>
<country xml:lang="fr">Brésil</country>
<wicri:regionArea>Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC</wicri:regionArea>
<placeName><region type="state">Santa Catarina</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Dal Pizzol, Felipe" sort="Dal Pizzol, Felipe" uniqKey="Dal Pizzol F" first="Felipe" last="Dal-Pizzol">Felipe Dal-Pizzol</name>
<affiliation wicri:level="1"><nlm:affiliation>Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil fdpizzol@gmail.com.</nlm:affiliation>
<country wicri:rule="url">Oman</country>
<wicri:regionArea>Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC</wicri:regionArea>
<wicri:noRegion>SC</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j">Clinical science (London, England : 1979)</title>
<idno type="eISSN">1470-8736</idno>
<imprint><date when="2019" type="published">2019</date>
</imprint>
</series>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals (MeSH)</term>
<term>Autophagy (drug effects)</term>
<term>Brain (drug effects)</term>
<term>Brain (pathology)</term>
<term>Cognitive Dysfunction (complications)</term>
<term>Cognitive Dysfunction (pathology)</term>
<term>Disease Models, Animal (MeSH)</term>
<term>Male (MeSH)</term>
<term>Mitochondria (drug effects)</term>
<term>Mitochondria (metabolism)</term>
<term>Mitochondria (pathology)</term>
<term>Mitochondrial Dynamics (drug effects)</term>
<term>Rats, Wistar (MeSH)</term>
<term>Rilmenidine (pharmacology)</term>
<term>Rosiglitazone (pharmacology)</term>
<term>Sepsis (complications)</term>
<term>Sepsis (pathology)</term>
<term>Sirolimus (pharmacology)</term>
<term>Survival Analysis (MeSH)</term>
<term>Up-Regulation (drug effects)</term>
<term>Up-Regulation (genetics)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Analyse de survie (MeSH)</term>
<term>Animaux (MeSH)</term>
<term>Autophagie (effets des médicaments et des substances chimiques)</term>
<term>Dynamique mitochondriale (effets des médicaments et des substances chimiques)</term>
<term>Dysfonctionnement cognitif (anatomopathologie)</term>
<term>Dysfonctionnement cognitif (complications)</term>
<term>Encéphale (anatomopathologie)</term>
<term>Encéphale (effets des médicaments et des substances chimiques)</term>
<term>Mitochondries (anatomopathologie)</term>
<term>Mitochondries (effets des médicaments et des substances chimiques)</term>
<term>Mitochondries (métabolisme)</term>
<term>Modèles animaux de maladie humaine (MeSH)</term>
<term>Mâle (MeSH)</term>
<term>Rat Wistar (MeSH)</term>
<term>Rilménidine (pharmacologie)</term>
<term>Rosiglitazone (pharmacologie)</term>
<term>Régulation positive (effets des médicaments et des substances chimiques)</term>
<term>Régulation positive (génétique)</term>
<term>Sepsie (anatomopathologie)</term>
<term>Sepsie (complications)</term>
<term>Sirolimus (pharmacologie)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Rilmenidine</term>
<term>Rosiglitazone</term>
<term>Sirolimus</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Dysfonctionnement cognitif</term>
<term>Encéphale</term>
<term>Mitochondries</term>
<term>Sepsie</term>
</keywords>
<keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>Cognitive Dysfunction</term>
<term>Sepsis</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Autophagy</term>
<term>Brain</term>
<term>Mitochondria</term>
<term>Mitochondrial Dynamics</term>
<term>Up-Regulation</term>
</keywords>
<keywords scheme="MESH" qualifier="effets des médicaments et des substances chimiques" xml:lang="fr"><term>Autophagie</term>
<term>Dynamique mitochondriale</term>
<term>Encéphale</term>
<term>Mitochondries</term>
<term>Régulation positive</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Up-Regulation</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Régulation positive</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Mitochondria</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Mitochondries</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Brain</term>
<term>Cognitive Dysfunction</term>
<term>Mitochondria</term>
<term>Sepsis</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Dysfonctionnement cognitif</term>
<term>Rilménidine</term>
<term>Rosiglitazone</term>
<term>Sepsie</term>
<term>Sirolimus</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Disease Models, Animal</term>
<term>Male</term>
<term>Rats, Wistar</term>
<term>Survival Analysis</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Analyse de survie</term>
<term>Animaux</term>
<term>Modèles animaux de maladie humaine</term>
<term>Mâle</term>
<term>Rat Wistar</term>
</keywords>
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<front><div type="abstract" xml:lang="en"><b>Background:</b>
 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.<b>Methods:</b>
 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<b>.</b>
<b>Results:</b>
 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 <i>ex vivo</i>
 oxygen consumption and the long-term cognitive impairment observed in sepsis survivors.<b>Conclusion:</b>
 Long-term impairment of brain function is temporally related to mitochondrial dysfunction. Activators of autophagy and mitochondrial biogenesis could rescue animals from cognitive impairment.</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">31527095</PMID>
<DateCompleted><Year>2020</Year>
<Month>05</Month>
<Day>14</Day>
</DateCompleted>
<DateRevised><Year>2020</Year>
<Month>05</Month>
<Day>14</Day>
</DateRevised>
<Article PubModel="Electronic-Print"><Journal><ISSN IssnType="Electronic">1470-8736</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>133</Volume>
<Issue>18</Issue>
<PubDate><Year>2019</Year>
<Month>09</Month>
<Day>30</Day>
</PubDate>
</JournalIssue>
<Title>Clinical science (London, England : 1979)</Title>
<ISOAbbreviation>Clin Sci (Lond)</ISOAbbreviation>
</Journal>
<ArticleTitle>Mitochondrial dysfunction is associated with long-term cognitive impairment in an animal sepsis model.</ArticleTitle>
<Pagination><MedlinePgn>1993-2004</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1042/CS20190351</ELocationID>
<Abstract><AbstractText><b>Background:</b>
 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.<b>Methods:</b>
 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<b>.</b>
<b>Results:</b>
 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 <i>ex vivo</i>
 oxygen consumption and the long-term cognitive impairment observed in sepsis survivors.<b>Conclusion:</b>
 Long-term impairment of brain function is temporally related to mitochondrial dysfunction. Activators of autophagy and mitochondrial biogenesis could rescue animals from cognitive impairment.</AbstractText>
<CopyrightInformation>© 2019 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Manfredini</LastName>
<ForeName>Andressa</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Constantino</LastName>
<ForeName>Larissa</ForeName>
<Initials>L</Initials>
<AffiliationInfo><Affiliation>Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Pinto</LastName>
<ForeName>Milton Castro</ForeName>
<Initials>MC</Initials>
<AffiliationInfo><Affiliation>Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Michels</LastName>
<ForeName>Monique</ForeName>
<Initials>M</Initials>
<Identifier Source="ORCID">0000-0001-8440-1976</Identifier>
<AffiliationInfo><Affiliation>Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Burger</LastName>
<ForeName>Henrique</ForeName>
<Initials>H</Initials>
<AffiliationInfo><Affiliation>Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Kist</LastName>
<ForeName>Luiza W</ForeName>
<Initials>LW</Initials>
<AffiliationInfo><Affiliation>Genomics and Molecular Biology Laboratory, Faculty of Biosciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, Brazil.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Postgraduate Program in Medicine and Health Sciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, Brazil.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Silva</LastName>
<ForeName>Milena Carvalho</ForeName>
<Initials>MC</Initials>
<AffiliationInfo><Affiliation>Laboratory of Bioenergetics, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Gomes</LastName>
<ForeName>Lara Mezzari</ForeName>
<Initials>LM</Initials>
<AffiliationInfo><Affiliation>Laboratory of Bioenergetics, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Dominguini</LastName>
<ForeName>Diogo</ForeName>
<Initials>D</Initials>
<AffiliationInfo><Affiliation>Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Steckert</LastName>
<ForeName>Amanda</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Simioni</LastName>
<ForeName>Carmen</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>Plant Cell Biology Laboratory, Department of Cell Biology, Embryology and Genetics, Federal University of Santa Catarina, Florianópolis, Brazil.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Bogo</LastName>
<ForeName>Mauricio</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Genomics and Molecular Biology Laboratory, Faculty of Biosciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, Brazil.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Postgraduate Program in Medicine and Health Sciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, Brazil.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Streck</LastName>
<ForeName>Emílio</ForeName>
<Initials>E</Initials>
<AffiliationInfo><Affiliation>Laboratory of Bioenergetics, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Barichello</LastName>
<ForeName>Tatiana</ForeName>
<Initials>T</Initials>
<AffiliationInfo><Affiliation>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.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>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.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Laboratory of Experimental Microbiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>de Quevedo</LastName>
<ForeName>João</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>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.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>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.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Neuroscience Graduate Program, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, U.S.A.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Singer</LastName>
<ForeName>Mervyn</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Bloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College London, London, United Kingdom.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ritter</LastName>
<ForeName>Cristiane</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Dal-Pizzol</LastName>
<ForeName>Felipe</ForeName>
<Initials>F</Initials>
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<AffiliationInfo><Affiliation>Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil fdpizzol@gmail.com.</Affiliation>
</AffiliationInfo>
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</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2019</Year>
<Month>09</Month>
<Day>24</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>England</Country>
<MedlineTA>Clin Sci (Lond)</MedlineTA>
<NlmUniqueID>7905731</NlmUniqueID>
<ISSNLinking>0143-5221</ISSNLinking>
</MedlineJournalInfo>
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<NameOfSubstance UI="D000077154">Rosiglitazone</NameOfSubstance>
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<Chemical><RegistryNumber>P67IM25ID8</RegistryNumber>
<NameOfSubstance UI="D000077769">Rilmenidine</NameOfSubstance>
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<Chemical><RegistryNumber>W36ZG6FT64</RegistryNumber>
<NameOfSubstance UI="D020123">Sirolimus</NameOfSubstance>
</Chemical>
</ChemicalList>
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<MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D001343" MajorTopicYN="N">Autophagy</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D001921" MajorTopicYN="N">Brain</DescriptorName>
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<QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D060825" MajorTopicYN="N">Cognitive Dysfunction</DescriptorName>
<QualifierName UI="Q000150" MajorTopicYN="Y">complications</QualifierName>
<QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D004195" MajorTopicYN="N">Disease Models, Animal</DescriptorName>
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<MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName>
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<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
<QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D063154" MajorTopicYN="N">Mitochondrial Dynamics</DescriptorName>
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<MeshHeading><DescriptorName UI="D017208" MajorTopicYN="N">Rats, Wistar</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000077769" MajorTopicYN="N">Rilmenidine</DescriptorName>
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<MeshHeading><DescriptorName UI="D000077154" MajorTopicYN="N">Rosiglitazone</DescriptorName>
<QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D018805" MajorTopicYN="N">Sepsis</DescriptorName>
<QualifierName UI="Q000150" MajorTopicYN="Y">complications</QualifierName>
<QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D020123" MajorTopicYN="N">Sirolimus</DescriptorName>
<QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D016019" MajorTopicYN="N">Survival Analysis</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D015854" MajorTopicYN="N">Up-Regulation</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
</MeshHeading>
</MeshHeadingList>
<KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">autophagy</Keyword>
<Keyword MajorTopicYN="Y">biogenesis</Keyword>
<Keyword MajorTopicYN="Y">brain dysfunction</Keyword>
<Keyword MajorTopicYN="Y">mitochondrial dysfunction</Keyword>
<Keyword MajorTopicYN="Y">sepsis</Keyword>
</KeywordList>
</MedlineCitation>
<PubmedData><History><PubMedPubDate PubStatus="received"><Year>2019</Year>
<Month>04</Month>
<Day>08</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="revised"><Year>2019</Year>
<Month>09</Month>
<Day>11</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="accepted"><Year>2019</Year>
<Month>09</Month>
<Day>16</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="pubmed"><Year>2019</Year>
<Month>9</Month>
<Day>19</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="medline"><Year>2020</Year>
<Month>5</Month>
<Day>15</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="entrez"><Year>2019</Year>
<Month>9</Month>
<Day>19</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
</History>
<PublicationStatus>epublish</PublicationStatus>
<ArticleIdList><ArticleId IdType="pubmed">31527095</ArticleId>
<ArticleId IdType="pii">CS20190351</ArticleId>
<ArticleId IdType="doi">10.1042/CS20190351</ArticleId>
</ArticleIdList>
</PubmedData>
</pubmed>
<affiliations><list><country><li>Brésil</li>
<li>Oman</li>
<li>Royaume-Uni</li>
<li>États-Unis</li>
</country>
<region><li>Angleterre</li>
<li>Grand Londres</li>
<li>Rio Grande do Sul</li>
<li>Santa Catarina</li>
<li>Texas</li>
</region>
<settlement><li>Londres</li>
</settlement>
<orgName><li>University College de Londres</li>
</orgName>
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<tree><country name="Brésil"><region name="Santa Catarina"><name sortKey="Manfredini, Andressa" sort="Manfredini, Andressa" uniqKey="Manfredini A" first="Andressa" last="Manfredini">Andressa Manfredini</name>
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<name sortKey="Barichello, Tatiana" sort="Barichello, Tatiana" uniqKey="Barichello T" first="Tatiana" last="Barichello">Tatiana Barichello</name>
<name sortKey="Bogo, Mauricio" sort="Bogo, Mauricio" uniqKey="Bogo M" first="Mauricio" last="Bogo">Mauricio Bogo</name>
<name sortKey="Bogo, Mauricio" sort="Bogo, Mauricio" uniqKey="Bogo M" first="Mauricio" last="Bogo">Mauricio Bogo</name>
<name sortKey="Burger, Henrique" sort="Burger, Henrique" uniqKey="Burger H" first="Henrique" last="Burger">Henrique Burger</name>
<name sortKey="Constantino, Larissa" sort="Constantino, Larissa" uniqKey="Constantino L" first="Larissa" last="Constantino">Larissa Constantino</name>
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<name sortKey="Ritter, Cristiane" sort="Ritter, Cristiane" uniqKey="Ritter C" first="Cristiane" last="Ritter">Cristiane Ritter</name>
<name sortKey="Silva, Milena Carvalho" sort="Silva, Milena Carvalho" uniqKey="Silva M" first="Milena Carvalho" last="Silva">Milena Carvalho Silva</name>
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<country name="États-Unis"><region name="Texas"><name sortKey="Barichello, Tatiana" sort="Barichello, Tatiana" uniqKey="Barichello T" first="Tatiana" last="Barichello">Tatiana Barichello</name>
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<country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Singer, Mervyn" sort="Singer, Mervyn" uniqKey="Singer M" first="Mervyn" last="Singer">Mervyn Singer</name>
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Mitochondrial dysfunction is associated with long-term cognitive impairment in an animal sepsis model.

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

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