Microglial activation elicits a negative affective state through prostaglandin-mediated modulation of striatal neurons

Institut for Lægemiddeldesign og Farmakologi

Microglial activation elicits a negative affective state through prostaglandin-mediated modulation of striatal neurons

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Standard

Microglial activation elicits a negative affective state through prostaglandin-mediated modulation of striatal neurons. / Klawonn, Anna M; Fritz, Michael; Castany, Silvia; Pignatelli, Marco; Canal, Carla; Similä, Fredrik; Tejeda, Hugo A; Levinsson, Julia; Jaarola, Maarit; Jakobsson, Johan; Hidalgo, Juan; Heilig, Markus; Bonci, Antonello; Engblom, David.

I: Immunity, Bind 54, Nr. 2, 2021, s. 225-234.e6.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Klawonn, AM, Fritz, M, Castany, S, Pignatelli, M, Canal, C, Similä, F, Tejeda, HA, Levinsson, J, Jaarola, M, Jakobsson, J, Hidalgo, J, Heilig, M, Bonci, A & Engblom, D 2021, 'Microglial activation elicits a negative affective state through prostaglandin-mediated modulation of striatal neurons', Immunity, bind 54, nr. 2, s. 225-234.e6. https://doi.org/10.1016/j.immuni.2020.12.016

APA

Klawonn, A. M., Fritz, M., Castany, S., Pignatelli, M., Canal, C., Similä, F., Tejeda, H. A., Levinsson, J., Jaarola, M., Jakobsson, J., Hidalgo, J., Heilig, M., Bonci, A., & Engblom, D. (2021). Microglial activation elicits a negative affective state through prostaglandin-mediated modulation of striatal neurons. Immunity, 54(2), 225-234.e6. https://doi.org/10.1016/j.immuni.2020.12.016

Vancouver

Klawonn AM, Fritz M, Castany S, Pignatelli M, Canal C, Similä F o.a. Microglial activation elicits a negative affective state through prostaglandin-mediated modulation of striatal neurons. Immunity. 2021;54(2):225-234.e6. https://doi.org/10.1016/j.immuni.2020.12.016

Author

Klawonn, Anna M ; Fritz, Michael ; Castany, Silvia ; Pignatelli, Marco ; Canal, Carla ; Similä, Fredrik ; Tejeda, Hugo A ; Levinsson, Julia ; Jaarola, Maarit ; Jakobsson, Johan ; Hidalgo, Juan ; Heilig, Markus ; Bonci, Antonello ; Engblom, David. / Microglial activation elicits a negative affective state through prostaglandin-mediated modulation of striatal neurons. I: Immunity. 2021 ; Bind 54, Nr. 2. s. 225-234.e6.

Bibtex

@article{a21e4813befc41a18c46c92f0f5551ff,

title = "Microglial activation elicits a negative affective state through prostaglandin-mediated modulation of striatal neurons",

abstract = "Microglia are activated in many neurological diseases and have been suggested to play an important role in the development of affective disorders including major depression. To investigate how microglial signaling regulates mood, we used bidirectional chemogenetic manipulations of microglial activity in mice. Activation of microglia in the dorsal striatum induced local cytokine expression and a negative affective state characterized by anhedonia and aversion, whereas inactivation of microglia blocked aversion induced by systemic inflammation. Interleukin-6 signaling and cyclooxygenase-1 mediated prostaglandin synthesis in the microglia were critical for the inflammation-induced aversion. Correspondingly, microglial activation led to a prostaglandin-dependent reduction of the excitability of striatal neurons. These findings demonstrate a mechanism by which microglial activation causes negative affect through prostaglandin-dependent modulation of striatal neurons and indicate that interference with this mechanism could milden the depressive symptoms in somatic and psychiatric diseases involving microglial activation.",

author = "Klawonn, {Anna M} and Michael Fritz and Silvia Castany and Marco Pignatelli and Carla Canal and Fredrik Simil{\"a} and Tejeda, {Hugo A} and Julia Levinsson and Maarit Jaarola and Johan Jakobsson and Juan Hidalgo and Markus Heilig and Antonello Bonci and David Engblom",

year = "2021",

doi = "10.1016/j.immuni.2020.12.016",

language = "English",

volume = "54",

pages = "225--234.e6",

journal = "Immunity",

issn = "1074-7613",

publisher = "Cell Press",

number = "2",

}

RIS

TY - JOUR

T1 - Microglial activation elicits a negative affective state through prostaglandin-mediated modulation of striatal neurons

AU - Klawonn, Anna M

AU - Fritz, Michael

AU - Castany, Silvia

AU - Pignatelli, Marco

AU - Canal, Carla

AU - Similä, Fredrik

AU - Tejeda, Hugo A

AU - Levinsson, Julia

AU - Jaarola, Maarit

AU - Jakobsson, Johan

AU - Hidalgo, Juan

AU - Heilig, Markus

AU - Bonci, Antonello

AU - Engblom, David

PY - 2021

Y1 - 2021

N2 - Microglia are activated in many neurological diseases and have been suggested to play an important role in the development of affective disorders including major depression. To investigate how microglial signaling regulates mood, we used bidirectional chemogenetic manipulations of microglial activity in mice. Activation of microglia in the dorsal striatum induced local cytokine expression and a negative affective state characterized by anhedonia and aversion, whereas inactivation of microglia blocked aversion induced by systemic inflammation. Interleukin-6 signaling and cyclooxygenase-1 mediated prostaglandin synthesis in the microglia were critical for the inflammation-induced aversion. Correspondingly, microglial activation led to a prostaglandin-dependent reduction of the excitability of striatal neurons. These findings demonstrate a mechanism by which microglial activation causes negative affect through prostaglandin-dependent modulation of striatal neurons and indicate that interference with this mechanism could milden the depressive symptoms in somatic and psychiatric diseases involving microglial activation.

AB - Microglia are activated in many neurological diseases and have been suggested to play an important role in the development of affective disorders including major depression. To investigate how microglial signaling regulates mood, we used bidirectional chemogenetic manipulations of microglial activity in mice. Activation of microglia in the dorsal striatum induced local cytokine expression and a negative affective state characterized by anhedonia and aversion, whereas inactivation of microglia blocked aversion induced by systemic inflammation. Interleukin-6 signaling and cyclooxygenase-1 mediated prostaglandin synthesis in the microglia were critical for the inflammation-induced aversion. Correspondingly, microglial activation led to a prostaglandin-dependent reduction of the excitability of striatal neurons. These findings demonstrate a mechanism by which microglial activation causes negative affect through prostaglandin-dependent modulation of striatal neurons and indicate that interference with this mechanism could milden the depressive symptoms in somatic and psychiatric diseases involving microglial activation.

U2 - 10.1016/j.immuni.2020.12.016

DO - 10.1016/j.immuni.2020.12.016

M3 - Journal article

C2 - 33476547

VL - 54

SP - 225-234.e6

JO - Immunity

JF - Immunity

SN - 1074-7613

IS - 2

ER -

ID: 269519696