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Isolation and Flow Cytometric Assessment of Neuroimmune Interactions in a Mini-Stroke Murine Model
Published on: June 20, 2025
De novo expression of dopamine D2 receptors on microglia after stroke
Jojanneke H J Huck1, Dorette Freyer2, Chotima Böttcher1
1Laboratory of Molecular Psychiatry, Department of Neuropsychiatry, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Abstract:
Dopamine is the predominant catecholamine in the brain and functions as a neurotransmitter. Dopamine is also a potent immune modulator. In this study, we have characterized the expression of dopamine receptors on murine microglia. We found that cultured primary microglia express dopamine D1, D2, D3, D4, and D5 receptors. We specifically focused on the D2 receptor (D2R), a major target of antipsychotic drugs. Whereas D2Rs were strongly expressed on striatal neurons in vivo, we did not detect any D2R expression on resident microglia in the healthy brains of wild-type mice or transgenic mice expressing the green fluorescent protein (GFP) under the control of the Drd2 promoter. However, cerebral ischemia induced the expression of D2R on Iba1-immunoreactive inflammatory cells in the infarct core and penumbra. Notably, D2R expression was confined to CD45(hi) cells, and GFP BM chimeras revealed that D2R was expressed on activated resident microglia as well as on peripherally derived macrophages in the ischemic brain. Importantly, the D2/3R agonist, pramipexole, enhanced the secretion of nitrite by cultured microglia in response to proinflammatory stimuli. Thus, dopamine may serve as a modulator of microglia function during neuroinflammation.
Insights
Dopamine receptors, particularly the D2 receptor (D2R), are expressed on microglia during neuroinflammation. Dopamine D2/3R agonists may modulate microglial immune responses in the brain.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Dopamine is a key neurotransmitter and immune modulator in the brain.
- Microglia are the primary immune cells in the central nervous system.
- Dopamine receptors are implicated in various neurological functions.
Purpose of the Study:
- To investigate the expression of dopamine receptors on murine microglia.
- To determine the role of dopamine D2 receptor (D2R) in microglia during neuroinflammation.
Main Methods:
- Primary microglia cultures were used to assess dopamine receptor expression.
- Immunohistochemistry and transgenic mice (GFP under Drd2 promoter) were employed.
- Cerebral ischemia model was used to induce neuroinflammation and study D2R expression in vivo.
Main Results:
- Cultured microglia express dopamine D1, D2, D3, D4, and D5 receptors.
- D2R is not detected on microglia in healthy brains but is induced after cerebral ischemia.
- D2R is expressed on activated microglia and infiltrating macrophages in the ischemic brain.
- Pramipexole (D2/3R agonist) enhanced nitrite secretion by microglia.
Conclusions:
- Dopamine receptors, including D2R, are expressed on microglia, particularly under inflammatory conditions.
- Dopamine signaling may modulate microglial function during neuroinflammation.
- D2R expression on microglia could represent a therapeutic target for neuroinflammatory diseases.
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