Complement receptor 2 is expressed in neural progenitor cells and regulates adult hippocampal neurogenesis.
Complement receptor 2 is expressed in neural progenitor cells and regulates adult hippocampal neurogenesis.
复制标题
DOI：
10.1523/jneurosci.3617-10.2011
复制
发表时间：
2011-03-16
期刊：
影响因子：
--
通讯作者：
Wyss-Coray T
中科院分区：
文献类型：
--
作者：
Moriyama M;Fukuhara T;Britschgi M;He Y;Narasimhan R;Villeda S;Molina H;Huber BT;Holers M;Wyss-Coray T
损伤和炎症是成人神经发生的有效调节因素。由于补体系统形成了关键的免疫途径，也可能在神经发育和神经变性中发挥关键功能，因此我们想知道补体受体是否调节神经发生。我们发现补体受体 2 (CR2)，传统上称为 B 淋巴细胞抗原受体的辅助受体，在齿状回的成体神经祖细胞 (NPC) 中表达。它的两种配体，C3d 和干扰素-α (IFN-α)，可以抑制野生型 NPC 的增殖，但不能抑制源自缺乏 Cr2 (Cr2−/−) 的小鼠的 NPC，表明 Cr2 表达功能正常。与野生型同窝小鼠相比，年轻和年老的 Cr2−/− 小鼠的基础神经发生显着增加，而脑内注射 C3d 导致野生型小鼠中增殖的神经母细胞数量少于 Cr2−/− 小鼠。我们得出结论，Cr2 调节海马神经发生，并提出与脑损伤或病毒感染相关的 C3d 和 IFN-α 产生增加可能会抑制神经发生。
Injury and inflammation are potent regulators of adult neurogenesis. As the complement system forms a key immune pathway that may also exert critical functions in neural development and neurodegeneration, we asked if complement receptors regulate neurogenesis. We discovered that complement receptor 2 (CR2), classically known as a co-receptor of the B lymphocyte antigen receptor, is expressed in adult neural progenitor cells (NPCs) of the dentate gyrus. Two of its ligands, C3d and interferon-α (IFN-α), inhibited proliferation of wildtype NPCs but not NPCs derived from mice lacking Cr2 (Cr2−/−) indicating functional Cr2 expression. Young and old Cr2−/− mice exhibited prominent increases in basal neurogenesis compared with wildtype littermates, while intracerebral injection of C3d resulted in fewer proliferating neuroblasts in wildtype than in Cr2−/− mice. We conclude that Cr2 regulates hippocampal neurogenesis and propose that increased C3d and IFN-α production associated with brain injury or viral infections may inhibit neurogenesis.