Institute of Neuroscience, Key Laboratory of Molecular Neurobiology of Ministry of Education and the Collaborative Innovation Center for Brain Science, Second Military Medical University, 200433, Shanghai, China.
Cell Death Dis. 2018 Feb 15;9(3):268. doi: 10.1038/s41419-018-0328-0.
The neural stem cells (NSCs) of the subventricular zone (SVZ) reside within a specialized niche critical for neurogenesis. Hemopexin, a plasma glycoprotein, has been extensively studied as a heme scavenger at the systemic level. However, little is known about its function in the central nervous system, especially in neurogenesis. In the present study, we demonstrate that deletion of hemopexin leads to neurogenic abnormalities in the SVZ/olfactory bulb (OB) pathway. The lateral ventricle is enlarged in hemopexin-deficient mice, and more apoptosis was observed in Dcx+ cells. Lineage differentiation of NSCs was also inhibited in the SVZ of hemopexin-deficient mice, with more stem cells stayed in an undifferentiated, GFAP+ radial glia-like cell stage. Moreover, hemopexin deletion resulted in impaired neuroblast migration in the rostral migratory stream. Furthermore, exogenous hemopexin protein inhibited apoptosis and promoted the migration and differentiation of cultured NSCs. Finally, immunohistochemical analysis demonstrated that deletion of hemopexin reduced the number of interneurons in the OB. Together, these results suggest a new molecular mechanism for the NSC niche that regulates adult neurogenesis in the SVZ/OB pathway. Our findings may benefit the understanding for olfactory system development.
神经干细胞（NSCs）位于侧脑室下区（SVZ），存在于一个对神经发生至关重要的特殊龛位中。血影蛋白是一种血浆糖蛋白，在全身水平上被广泛研究作为血红素清除剂。然而，关于其在中枢神经系统中的功能，特别是在神经发生中的功能，知之甚少。在本研究中，我们证明了血影蛋白的缺失导致 SVZ/嗅球（OB）通路中的神经发生异常。hemopexin 缺陷型小鼠的侧脑室增大，Dcx+细胞中观察到更多的细胞凋亡。NSCs 的谱系分化也在 hemopexin 缺陷型小鼠的 SVZ 中受到抑制，更多的干细胞停留在未分化的、GFAP+放射状胶质样细胞阶段。此外，hemopexin 缺失导致前体细胞在向嗅球迁移过程中受损。此外，外源性血影蛋白蛋白抑制凋亡并促进培养的 NSCs 的迁移和分化。最后，免疫组织化学分析表明，hemopexin 的缺失减少了 OB 中的中间神经元数量。总之，这些结果表明了一个调节 SVZ/OB 通路中成年神经发生的 NSC 龛位的新分子机制。我们的发现可能有助于理解嗅觉系统的发育。
