title: Complement receptor 2 is expressed in neural progenitor cells and regulates adult hippocampal neurogenesis.
abstract: Injury and inflammation are potent regulators of adult neurogenesis. As the complement system forms a key immune pathway that may also exert critical functions in neural development and neurodegeneration, we asked whether complement receptors regulate neurogenesis. We discovered that complement receptor 2 (CR2), classically known as a coreceptor of the B-lymphocyte antigen receptor, is expressed in adult neural progenitor cells (NPCs) of the dentate gyrus. Two of its ligands, C3d and interferon-α (IFN-α), inhibited proliferation of wild-type NPCs but not NPCs derived from mice lacking Cr2 (Cr2(-/-)), indicating functional Cr2 expression. Young and old Cr2(-/-) mice exhibited prominent increases in basal neurogenesis compared with wild-type littermates, whereas intracerebral injection of C3d resulted in fewer proliferating neuroblasts in wild-type than in Cr2(-/-) mice. We conclude that Cr2 regulates hippocampal neurogenesis and propose that increased C3d and IFN-α production associated with brain injury or viral infections may inhibit neurogenesis.
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, California 94305, USA.
authors.forename: Maiko
authors.initials: M
authors.lastname: Moriyama
authors.forename: Takeshi
authors.initials: T
authors.lastname: Fukuhara
authors.forename: Markus
authors.initials: M
authors.lastname: Britschgi
authors.forename: Yingbo
authors.initials: Y
authors.lastname: He
authors.forename: Ramya
authors.initials: R
authors.lastname: Narasimhan
authors.forename: Saul
authors.initials: S
authors.lastname: Villeda
authors.forename: Hector
authors.initials: H
authors.lastname: Molina
authors.forename: Brigitte T
authors.initials: BT
authors.lastname: Huber
authors.forename: Mike
authors.initials: M
authors.lastname: Holers
authors.forename: Tony
authors.initials: T
authors.lastname: Wyss-Coray
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D015933:Complement C3d / Q000378:metabolism; D006624:Hippocampus / Q000502:physiology*; D007150:Immunohistochemistry; D016898:Interferon-alpha / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D058953:Neural Stem Cells / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D017464:Receptors, Complement 3d / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016898:Interferon-alpha; D017464:Receptors, Complement 3d; D015933:Complement C3d