4.7 Article

Complement Receptor 2 Is Expressed in Neural Progenitor Cells and Regulates Adult Hippocampal Neurogenesis

Journal

JOURNAL OF NEUROSCIENCE
Volume 31, Issue 11, Pages 3981-3989

Publisher

SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.3617-10.2011

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Funding

  1. Japanese Society for Promotion of Sciences
  2. National Institute on Aging [AG20603, AG27505]

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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-alpha (IFN-alpha), 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-alpha production associated with brain injury or viral infections may inhibit neurogenesis.

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