Department of Neurobiology and Behavior, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, 371-8511, Japan.
Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata, Japan.
Eur J Neurosci. 2017 Sep;46(6):2214-2228. doi: 10.1111/ejn.13668. Epub 2017 Sep 7.
F-actin-binding protein drebrin has two major isoforms: drebrin A and drebrin E. Drebrin A is the major isoform in the adult brain and is highly concentrated in dendritic spines, regulating spine morphology and synaptic plasticity. Conversely, drebrin E is the major isoform in the embryonic brain and regulates neuronal morphological differentiation, but it is also expressed in neurogenic regions of the adult brain. The subventricular zone (SVZ) is one of the brain regions where adult neurogenesis occurs. Neuroblasts migrate to the olfactory bulb (OB) and integrate into existing neuronal networks, after which drebrin expression changes from E to A, suggesting that drebrin E plays a specific role in neuroblasts in the adult brain. Therefore, to understand the role of drebrin E in the adult brain, we immunohistochemically analyzed adult neurogenesis using drebrin-null-mutant (DXKO) mice. In DXKO mice, the number of neuroblasts and cell proliferation decreased, although cell death remained unchanged. These results suggest that drebrin E regulates cell proliferation in the adult SVZ. Surprisingly, the decreased number of neuroblasts in the SVZ did not result in less neurons in the OB. This was because the survival rate of newly generated neurons in the OB increased in DXKO mice. Additionally, when neuroblasts reached the OB, the change in the migratory pathway from tangential to radial was partly disturbed in DXKO mice. These results suggest that drebrin E is involved in a chain migration of neuroblasts.
肌动蛋白结合蛋白 drebrin 有两种主要的同工型：drebrin A 和 drebrin E。Drebrin A 是成年大脑中的主要同工型，高度集中在树突棘中，调节棘形态和突触可塑性。相反，drebrin E 是胚胎大脑中的主要同工型，调节神经元形态分化，但也在成年大脑的神经发生区域表达。室下区 (SVZ) 是发生成人神经发生的脑区之一。神经前体细胞迁移到嗅球 (OB) 并整合到现有的神经元网络中，之后 drebrin 的表达从 E 转变为 A，表明 drebrin E 在成年大脑中的神经前体细胞中发挥特定作用。因此，为了了解 drebrin E 在成年大脑中的作用，我们使用 drebrin 缺失突变 (DXKO) 小鼠对成年神经发生进行了免疫组织化学分析。在 DXKO 小鼠中，神经前体细胞的数量和细胞增殖减少，尽管细胞死亡保持不变。这些结果表明 drebrin E 调节成年 SVZ 中的细胞增殖。令人惊讶的是，SVZ 中神经前体细胞数量的减少并没有导致 OB 中神经元数量的减少。这是因为在 DXKO 小鼠中，OB 中新生成的神经元的存活率增加了。此外，当神经前体细胞到达 OB 时，在 DXKO 小鼠中，从切线到放射状的迁移途径的变化部分受到干扰。这些结果表明 drebrin E 参与了神经前体细胞的链式迁移。
