Microglial activation elicits a negative affective state through prostaglandin-mediated modulation of striatal neurons
(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)
- author
- organization
- publishing date
- 2021
- 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}}, }