title: Role of complement anaphylatoxin receptors (C3aR, C5aR) in the development of the rat cerebellum.
abstract: There is now strong evidence for non-immune or inflammatory functions of complement, notably in the central nervous system. In particular, it has been recently reported that the anaphylatoxin receptors C3aR and C5aR are transiently expressed in the cerebellar cortex of newborn rat, suggesting that anaphylatoxins are involved in the histogenesis of the cerebellum. In the present study, we have investigated the effects of C3aR and C5aR agonists and antagonists on the development of the cerebellum of 11-12-day-old rats in vivo and in vitro. Sub-dural injection of C3aR and C5aR agonists at the surface of the cerebellum transiently modified the thickness of the cortical layers. The C5aR agonist provoked an enlargement of the external granule cell layer (EGL) that was due to increased proliferation of immature granule neurons. Conversely, the C3aR agonist decreased the thickness of the EGL and increased the thickness of the internal granule cell layer (IGL), suggesting that C3a accelerates the migration process of granule cells from the EGL to the IGL. Video-microscopy examination of cultured granule neurons confirmed the role of C3aR in cell motility. These results provide clear evidence for the involvement of anaphylatoxin receptors in the histogenesis of the cerebellar cortex.
authors.affiliation: Inserm U413, Laboratory of Cellular and Molecular Neuroendocrinology, 76821 Mont-Saint-Aignan, France. magalie.benard@univ-rouen.fr
authors.forename: Magalie
authors.initials: M
authors.lastname: Bénard
authors.forename: Emilie
authors.initials: E
authors.lastname: Raoult
authors.forename: David
authors.initials: D
authors.lastname: Vaudry
authors.forename: Jérome
authors.initials: J
authors.lastname: Leprince
authors.forename: Anthony
authors.initials: A
authors.lastname: Falluel-Morel
authors.forename: Bruno J
authors.initials: BJ
authors.lastname: Gonzalez
authors.forename: Ludovic
authors.initials: L
authors.lastname: Galas
authors.forename: Hubert
authors.initials: H
authors.lastname: Vaudry
authors.forename: Marc
authors.initials: M
authors.lastname: Fontaine
mesh_terms: D000706:Anaphylatoxins / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000254:growth & development*; D007150:Immunohistochemistry; D009474:Neurons / Q000145:classification / Q000276:immunology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044087:Receptor, Anaphylatoxin C5a / Q000819:agonists / Q000276:immunology* / Q000378:metabolism; D011951:Receptors, Complement / Q000819:agonists / Q000276:immunology* / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000276:immunology
chemical_list: D000706:Anaphylatoxins; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; D043562:Receptors, G-Protein-Coupled; C532341:anaphylatoxin receptor C3a, rat; C085567:complement C3a receptor