Article
- The EMBO Journal (2006) 25, 1364 - 1374
- doi:10.1038/sj.emboj.7601004
Published online: 23 February 2006
Subject Categories:
Complement: a novel factor in basal and ischemia-induced neurogenesis
Yalda Rahpeymai1, Max Albert Hietala1, Ulrika Wilhelmsson2, Andrew Fotheringham3, Ioan Davies3, Ann-Katrin Nilsson1, Jörg Zwirner4, Rick A Wetsel5, Craig Gerard6, Milos Pekny2 and Marcela Pekna1
- Institute of Biomedicine, Department of Medical Chemistry and Cell Biology, Sahlgrenska Academy at Göteborg University, Göteborg, Sweden
- The Arvid Carlsson Institute for Neuroscience, Institute of Neuroscience and Physiology, Section for Clinical Neuroscience and Rehabilitation, Sahlgrenska Academy at Göteborg University, Göteborg, Sweden
- School of Medicine and School of Biological Sciences, University of Manchester, Manchester, UK
- Department of Immunology, Georg-August-University Göttingen, Göttingen, Germany
- Research Center for Immunology and Autoimmune Diseases, Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas-Houston, Houston, TX, USA
- Pulmonary Division, Department of Pediatrics, Children's Hospital, Harvard Medical School, Boston, MA, USA
Correspondence to:
Marcela Pekna, Department of Medical Chemistry and Cell Biology, Sahlgrenska Academy at Göteborg University, Box 440, 405 30 Göteborg, Sweden. Tel.: +46 31 773 3581; Fax: +46 31 416 108; E-mail: Marcela.Pekna@medkem.gu.se
Received 16 August 2005; Accepted 24 January 2006
Abstract
Through its involvement in inflammation, opsonization, and cytolysis, the complement protects against infectious agents. Although most of the complement proteins are synthesized in the central nervous system (CNS), the role of the complement system in the normal or ischemic CNS remains unclear. Here we demonstrate for the first time that neural progenitor cells and immature neurons express receptors for complement fragments C3a and C5a (C3a receptor (C3aR) and C5a receptor). Mice that are deficient in complement factor C3 (C3-/-) lack C3a and are unable to generate C5a through proteolytic cleavage of C5 by C5-convertase. Intriguingly, basal neurogenesis is decreased both in C3-/- mice and in mice lacking C3aR or mice treated with a C3aR antagonist. The C3-/- mice had impaired ischemia-induced neurogenesis both in the subventricular zone, the main source of neural progenitor cells in adult brain, and in the ischemic region, despite normal proliferative response and larger infarct volumes. Thus, in the adult mammalian CNS, complement activation products promote both basal and ischemia-induced neurogenesis.
Keywords:
- C3,
- cerebral ischemia,
- complement system,
- mice,
- neurogenesis
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