Complement: a Novel Factor in Basal and Ischemia-induced Neurogenesis

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2006 Feb 25

PMID 16498410

Citations 131

Authors

Yalda Rahpeymai

Max Albert Hietala

Ulrika Wilhelmsson

Andrew Fotheringham

Ioan Davies

Ann-Katrin Nilsson

Jorg Zwirner

Rick A Wetsel

Craig Gerard

Milos Pekny

Marcela Pekna

Affiliations

Soon will be listed here.

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.

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