De novo expression of dopamine D2 receptors on microglia after stroke

Jojanneke H J Huck, Dorette Freyer, Chotima Böttcher, Mihovil Mladinov, Claudia Muselmann-Genschow, Mareike Thielke, Nadine Gladow, Dana Bloomquist, Philipp Mergenthaler, Josef Priller

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.

Original languageEnglish
Pages (from-to)1804-11
Number of pages8
JournalJournal of Cerebral Blood Flow and Metabolism
Volume35
Issue number11
Early online date24 Jun 2015
DOIs
Publication statusE-pub ahead of print - 24 Jun 2015

Keywords / Materials (for Non-textual outputs)

  • Animals
  • Benzothiazoles
  • Bone Marrow Cells
  • Cells, Cultured
  • Chimera
  • Dopamine Agonists
  • Green Fluorescent Proteins
  • Infarction, Middle Cerebral Artery
  • Leukocyte Common Antigens
  • Mice
  • Mice, Inbred C57BL
  • Microglia
  • Neurons
  • Promoter Regions, Genetic
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Stroke
  • Journal Article
  • Research Support, Non-U.S. Gov't

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