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Michela Matteoli1, Davide Pozzi2
1Humanitas Clinical and Research Center - IRCCS, Rozzano, Milan, Italy; CNR Institute of Neuroscience, Milano, Italy.
Abstract:
The immune system actively regulates brain activity through the engagement of immune cells and immunomodulatory molecules. In this issue of Immunity, Klawonn et al. show that the activation of microglia in the striatum triggers an IL-6-mediated autocrine loop and the release of prostaglandins, which in turn induce a negative affective state via the stimulation of medium spiny neurons.
Insights
Brain immune cells, microglia, activate an IL-6 loop in the striatum. This triggers prostaglandins, causing negative affective states by stimulating specific neurons.
Area of Science:
- Neuroimmunology
- Affective Neuroscience
Background:
- The brain's immune system, involving microglia and signaling molecules, actively influences neural function.
- Understanding the precise mechanisms linking immune activity to brain states is crucial.
Purpose of the Study:
- To investigate how microglia activation in the striatum impacts affective states.
- To elucidate the molecular pathways involved in immune-mediated regulation of brain activity.
Main Methods:
- Utilized mouse models to study microglia activation in the striatum.
- Analyzed the roles of Interleukin-6 (IL-6) and prostaglandins in affective state regulation.
Main Results:
- Microglia activation in the striatum initiates an Interleukin-6 (IL-6) autocrine signaling pathway.
- This IL-6 loop leads to prostaglandin release.
- Prostaglandins stimulate medium spiny neurons, inducing a negative affective state.
Conclusions:
- Microglial activation in the striatum can directly drive negative affective states through an IL-6 and prostaglandin-dependent mechanism.
- This study highlights a novel pathway for immune system regulation of mood and behavior.
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