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Updated: Nov 20, 2025
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Microglial activation elicits a negative affective state through prostaglandin-mediated modulation of striatal
Anna M Klawonn1, Michael Fritz2, Silvia Castany3
1Department of Biomedical and Clinical Sciences, Linköping University, 58185 Linköping, Sweden; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA.
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.
Insights
Microglial activation in the brain can cause depression-like symptoms by altering neuron activity. Targeting this pathway may help treat mood disorders linked to inflammation.
Area of Science:
- Neuroscience
- Immunology
- Psychiatry
Background:
- Microglia, the brain's immune cells, are implicated in neurological diseases and mood disorders like depression.
- Understanding microglial signaling's role in affective disorders is crucial for developing new treatments.
Purpose of the Study:
- To investigate how manipulating microglial activity influences mood and behavior in mice.
- To elucidate the specific molecular pathways involved in microglial regulation of affective states.
Main Methods:
- Bidirectional chemogenetic techniques were used to control microglial activity in the mouse dorsal striatum.
- Behavioral tests assessed affective states (anhedonia, aversion).
- Molecular analyses identified key signaling molecules like Interleukin-6 and prostaglandins.
Main Results:
- Activating microglia in the dorsal striatum induced negative affect and cytokine expression.
- Inactivating microglia blocked inflammation-induced aversion.
- Interleukin-6 and prostaglandin synthesis by microglia were essential for aversion.
- Microglial activation reduced striatal neuron excitability via prostaglandins.
Conclusions:
- Microglial activation drives negative affect through prostaglandin-mediated suppression of striatal neuron activity.
- Targeting microglial prostaglandin signaling offers a potential therapeutic strategy for depression and other disorders involving microglial activation.
