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

• 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.

Nyckelord

Animals

Central Nervous System

cytology

metabolism

Complement Activation

Complement C3a

genetics

physiology

Complement C5a

genetics

physiology

Female

Ischemia

pathology

Male

Mice

Mice

Inbred C57BL

Mice

Knockout

Neurons

cytology

metabolism

Receptor

Anaphylatoxin C5a

genetics

metabolism

Receptors

Complement

antagonists & inhibitors

genetics

metabolism

Stem Cells

cytology

metabolism

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art (ämneskategori)