<scp>G</scp>enetic deletion of x<scp>CT</scp> attenuates peripheral and central inflammation and mitigates <scp>LPS</scp>‐induced sickness and depressive‐like behavior in mice

DOI HANDLE Web Site Web Site PubMed 被引用文献5件 参考文献62件
  • Yun Zhou
    Department of Molecular Medicine Institute of Basic Medical Sciences, University of Oslo Oslo 0372 Norway
  • Sigrid Ottestad‐Hansen
    Department of Molecular Medicine Institute of Basic Medical Sciences, University of Oslo Oslo 0372 Norway
  • Giulia Albertini
    Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information Center for Neurosciences (C4N), Vrije Universiteit Brussel Brussels 1090 Belgium
  • Gamze Ates
    Department of In Vitro Toxicology and Dermato‐cosmetology Vrije Universiteit Brussel Brussels 1090 Belgium
  • Lauren Deneyer
    Department of Pharmaceutical Biotechnology and Molecular Biology Center for Neurosciences (C4N), Vrije Universiteit Brussel Brussels 1090 Belgium
  • Thomas Demuyser
    Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information Center for Neurosciences (C4N), Vrije Universiteit Brussel Brussels 1090 Belgium
  • Hideyo Sato
    Laboratory of Biochemistry and Molecular Biology, Department of Medical Technology Niigata University Niigata 951‐8518 Japan
  • Eduard Bentea
    Department of Pharmaceutical Biotechnology and Molecular Biology Center for Neurosciences (C4N), Vrije Universiteit Brussel Brussels 1090 Belgium
  • Laura Walrave
    Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information Center for Neurosciences (C4N), Vrije Universiteit Brussel Brussels 1090 Belgium
  • Ilse Smolders
    Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information Center for Neurosciences (C4N), Vrije Universiteit Brussel Brussels 1090 Belgium
  • Niels C. Danbolt
    Department of Molecular Medicine Institute of Basic Medical Sciences, University of Oslo Oslo 0372 Norway
  • Ann Massie
    Department of Pharmaceutical Biotechnology and Molecular Biology Center for Neurosciences (C4N), Vrije Universiteit Brussel Brussels 1090 Belgium
  • Dimitri De Bundel
    Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information Center for Neurosciences (C4N), Vrije Universiteit Brussel Brussels 1090 Belgium
  • Experimental Pharmacology
  • Faculty of Medicine and Pharmacy
  • Pharmaceutical and Pharmacological Sciences

書誌事項

公開日
2018-04-25
資源種別
journal article
権利情報
  • http://onlinelibrary.wiley.com/termsAndConditions#vor
DOI
  • 10.1002/glia.23343
公開者
Wiley

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説明

<jats:title>Abstract</jats:title><jats:p>The communication between the immune and central nervous system (CNS) is affected in many neurological disorders. Peripheral injections of the endotoxin lipopolysaccharide (LPS) are widely used to study this communication: an LPS challenge leads to a biphasic syndrome that starts with acute sickness and is followed by persistent brain inflammation and chronic behavioral alterations such as depressive‐like symptoms. <jats:italic>In vitro</jats:italic>, the response to LPS treatment has been shown to involve enhanced expression of system <jats:inline-graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="graphic/glia23343-math-0002.png" xlink:title="urn:x-wiley:08941491:media:glia23343:glia23343-math-0002"/>. This cystine‐glutamate antiporter, with xCT as specific subunit, represents the main glial provider of extracellular glutamate in mouse hippocampus. Here we injected male xCT knockout and wildtype mice with a single intraperitoneal dose of 5 mg/kg LPS. LPS‐injection increased hippocampal xCT expression but did not alter the mainly astroglial localization of the xCT protein. Peripheral and central inflammation (as defined by cytokine levels and morphological activation of microglia) as well as LPS‐induced sickness and depressive‐like behavior were significantly attenuated in xCT‐deficient mice compared with wildtype mice. Our study is the first to demonstrate the involvement of system <jats:inline-graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="graphic/glia23343-math-0003.png" xlink:title="urn:x-wiley:08941491:media:glia23343:glia23343-math-0003"/> in peripheral and central inflammation <jats:italic>in vivo</jats:italic> and the potential therapeutic relevance of its inhibition in brain disorders characterized by peripheral and central inflammation, such as depression.</jats:p>

収録刊行物

  • Glia

    Glia 66 (9), 1845-1861, 2018-04-25

    Wiley

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