title: De novo expression of dopamine D2 receptors on microglia after stroke.
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.
authors.affiliation: Laboratory of Molecular Psychiatry, Department of Neuropsychiatry, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Jojanneke H J
authors.initials: JH
authors.lastname: Huck
authors.affiliation: Departments of Experimental Neurology, Neurology and Center for Stroke Research, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Dorette
authors.initials: D
authors.lastname: Freyer
authors.affiliation: Laboratory of Molecular Psychiatry, Department of Neuropsychiatry, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Chotima
authors.initials: C
authors.lastname: Böttcher
authors.affiliation: Laboratory of Molecular Psychiatry, Department of Neuropsychiatry, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Mihovil
authors.initials: M
authors.lastname: Mladinov
authors.affiliation: Departments of Experimental Neurology, Neurology and Center for Stroke Research, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Muselmann-Genschow
authors.affiliation: Departments of Experimental Neurology, Neurology and Center for Stroke Research, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Mareike
authors.initials: M
authors.lastname: Thielke
authors.affiliation: Laboratory of Molecular Psychiatry, Department of Neuropsychiatry, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Gladow
authors.affiliation: Laboratory of Molecular Psychiatry, Department of Neuropsychiatry, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Dana
authors.initials: D
authors.lastname: Bloomquist
authors.affiliation: Departments of Experimental Neurology, Neurology and Center for Stroke Research, Charité-Universitätsmedizin Berlin, Berlin, Germany.|Cluster of Excellence 'NeuroCure', Berlin, Germany.|Biological Sciences, Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Philipp
authors.initials: P
authors.lastname: Mergenthaler
authors.affiliation: Laboratory of Molecular Psychiatry, Department of Neuropsychiatry, Charité-Universitätsmedizin Berlin, Berlin, Germany.|Cluster of Excellence 'NeuroCure', Berlin, Germany.|BIH and DZNE, Berlin, Germany.
authors.forename: Josef
authors.initials: J
authors.lastname: Priller
mesh_terms: D000818:Animals; D052160:Benzothiazoles / Q000494:pharmacology; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D002678:Chimera; D018491:Dopamine Agonists / Q000494:pharmacology; D049452:Green Fluorescent Proteins; D020244:Infarction, Middle Cerebral Artery / Q000235:genetics / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects; D000077487:Pramipexole; D011401:Promoter Regions, Genetic / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics*; D050637:Receptors, Dopamine D3 / Q000187:drug effects; D020521:Stroke / Q000235:genetics* / Q000378:metabolism*
chemical_list: D052160:Benzothiazoles; D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D049452:Green Fluorescent Proteins; D000077487:Pramipexole; D017493:Leukocyte Common Antigens