Complement: a novel factor in basal and ischemia-induced neurogenesis

EMBO J. 2006 Mar 22;25(6):1364-74. doi: 10.1038/sj.emboj.7601004. Epub 2006 Feb 23.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Central Nervous System / cytology
  • Central Nervous System / metabolism
  • Complement Activation
  • Complement C3a / genetics
  • Complement C3a / physiology*
  • Complement C5a / genetics
  • Complement C5a / physiology*
  • Female
  • Ischemia / pathology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neurons / cytology*
  • Neurons / metabolism
  • Receptor, Anaphylatoxin C5a / genetics
  • Receptor, Anaphylatoxin C5a / metabolism*
  • Receptors, Complement / antagonists & inhibitors
  • Receptors, Complement / genetics
  • Receptors, Complement / metabolism*
  • Stem Cells / cytology*
  • Stem Cells / metabolism

Substances

  • Receptor, Anaphylatoxin C5a
  • Receptors, Complement
  • Complement C3a
  • Complement C5a