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.
Institute of Biomedicine, Department of Medical Chemistry and Cell Biology, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden.
Yalda
Y
Rahpeymai
Max Albert
MA
Hietala
Ulrika
U
Wilhelmsson
Andrew
A
Fotheringham
Ioan
I
Davies
Ann-Katrin
AK
Nilsson
Jörg
J
Zwirner
Rick A
RA
Wetsel
Craig
C
Gerard
Milos
M
Pekny
Marcela
M
Pekna
D000818:Animals; D002490:Central Nervous System / Q000166:cytology / Q000378:metabolism; D003167:Complement Activation; D015926:Complement C3a / Q000235:genetics / Q000502:physiology*; D015936:Complement C5a / Q000235:genetics / Q000502:physiology*; D005260:Female; D007511:Ischemia / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D044087:Receptor, Anaphylatoxin C5a / Q000235:genetics / Q000378:metabolism*; D011951:Receptors, Complement / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; D015926:Complement C3a; D015936:Complement C5a