Interferon-ɣ mediated signaling in the brain endothelium is critical for inflammation-induced aversion

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Fritz, Michael,1981-Linköpings universitet,Centrum för social och affektiv neurovetenskap,Medicinska fakulteten (author)

Interferon-ɣ mediated signaling in the brain endothelium is critical for inflammation-induced aversion

Article/chapterEnglish2018

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Maryland Heights :Academic Press,2018
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LIBRIS-ID:oai:DiVA.org:liu-143812
https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-143812URI
https://doi.org/10.1016/j.bbi.2017.08.020DOI

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Language:English
Summary in:English

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Funding agencies: European Research Council; Swedish Medical Research Council; Knut and Alice Wallenberg foundation; Swedish Brain foundation; Parkinsonstiftelsen; Region Ostergotland
Systemic inflammation elicits malaise and a negative affective state. The mechanism underpinning the aversive component of inflammation include cerebral prostaglandin synthesis and modulation of dopaminergic reward circuits, but the messengers that mediate the signaling between the peripheral inflammation and the brain have not been sufficiently characterized. Here we investigated the role of interferon-ɣ (IFN-ɣ) in the aversive response to systemic inflammation induced by a low dose (10μg/kg) of lipopolysaccharide (LPS) in mice. LPS induced IFN-ɣ expression in the blood and deletion of IFN-ɣ or its receptor prevented the development of conditioned place aversion to LPS. LPS induced expression of the chemokine Cxcl10 in the striatum of normal mice, but this induction was absent in mice lacking IFN-ɣ receptors or Myd88 in blood brain barrier endothelial cells. Furthermore, inflammation-induced aversion was blocked in mice lacking Cxcl10 or its receptor Cxcr3. Finally, mice with a selective deletion of the IFN-ɣ receptor in brain endothelial cells did not develop inflammation-induced aversion, demonstrating that the brain endothelium is the critical site of IFN-ɣ action. Collectively, these findings show that circulating IFN-ɣ that binds to receptors on brain endothelial cells and induces Cxcl10, is a central link in the signaling chain eliciting inflammation-induced aversion.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Farmakologi och toxikologi hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Pharmacology and Toxicology hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Neurovetenskaper hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Neurosciences hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Immunologi inom det medicinska området hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Immunology in the medical area hsv//eng
NATURVETENSKAP Biologi Immunologi hsv//swe
NATURAL SCIENCES Biological Sciences Immunology hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Cell- och molekylärbiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Cell and Molecular Biology hsv//eng
Aversion; Behavior; Chemokines; Depression; Endothelium; Interferon; Lipopolysaccharide; Sickness

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Klawonn, Anna,1985-Linköpings universitet,Centrum för social och affektiv neurovetenskap,Medicinska fakulteten(Swepub:liu)annkl78 (author)
Jaarola, Maarit,1959-Linköpings universitet,Centrum för social och affektiv neurovetenskap,Medicinska fakulteten(Swepub:liu)maaja88 (author)
Engblom, DavidLinköpings universitet,Medicinska fakulteten,Centrum för social och affektiv neurovetenskap(Swepub:liu)daven69 (author)
Linköpings universitetCentrum för social och affektiv neurovetenskap (creator_code:org_t)

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In:Brain, behavior, and immunityMaryland Heights : Academic Press67, s. 54-580889-15911090-2139

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