Bénard Magalie, Raoult Emilie, Vaudry David, Leprince Jérome, Falluel-Morel Anthony, Gonzalez Bruno J, Galas Ludovic, Vaudry Hubert, Fontaine Marc
Inserm U413, Laboratory of Cellular and Molecular Neuroendocrinology, 76821 Mont-Saint-Aignan, France.
Mol Immunol. 2008 Aug;45(14):3767-74. doi: 10.1016/j.molimm.2008.05.027. Epub 2008 Jul 16.
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.
目前有强有力的证据表明补体具有非免疫或炎症功能，尤其是在中枢神经系统中。特别值得一提的是，最近有报道称过敏毒素受体C3aR和C5aR在新生大鼠的小脑皮质中短暂表达，这表明过敏毒素参与了小脑的组织发生过程。在本研究中，我们研究了C3aR和C5aR激动剂及拮抗剂对11 - 12日龄大鼠小脑体内和体外发育的影响。在小脑表面硬膜下注射C3aR和C5aR激动剂会短暂改变皮质层的厚度。C5aR激动剂会导致外颗粒细胞层（EGL）增厚，这是由于未成熟颗粒神经元的增殖增加所致。相反，C3aR激动剂会使EGL厚度减小，而内颗粒细胞层（IGL）厚度增加，这表明C3a加速了颗粒细胞从EGL向IGL的迁移过程。对培养的颗粒神经元进行视频显微镜检查证实了C3aR在细胞运动中的作用。这些结果为过敏毒素受体参与小脑皮质的组织发生提供了明确证据。
