Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

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 LU and Jakobsson, Johan LU orcid , et al. (2021) In Immunity 54(2). p.225-234
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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Immunity
volume
54
issue
2
pages
225 - 234
publisher
Cell Press
external identifiers
  • pmid:33476547
  • scopus:85100426384
ISSN
1074-7613
DOI
10.1016/j.immuni.2020.12.016
language
English
LU publication?
yes
additional info
Copyright © 2020 Elsevier Inc. All rights reserved.
id
0e0f5bd3-6391-4073-8a83-a2906853a73b
date added to LUP
2021-01-26 09:45:10
date last changed
2024-05-30 05:21:49
@article{0e0f5bd3-6391-4073-8a83-a2906853a73b,
  abstract     = {{<p>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.</p>}},
  author       = {{Klawonn, Anna M and Fritz, Michael and Castany, Silvia and Pignatelli, Marco and Canal, Carla and Similä, Fredrik and Tejeda, Hugo A and Levinsson, Julia and Jaarola, Maarit and Jakobsson, Johan and Hidalgo, Juan and Heilig, Markus and Bonci, Antonello and Engblom, David}},
  issn         = {{1074-7613}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{225--234}},
  publisher    = {{Cell Press}},
  series       = {{Immunity}},
  title        = {{Microglial activation elicits a negative affective state through prostaglandin-mediated modulation of striatal neurons}},
  url          = {{http://dx.doi.org/10.1016/j.immuni.2020.12.016}},
  doi          = {{10.1016/j.immuni.2020.12.016}},
  volume       = {{54}},
  year         = {{2021}},
}