Thomas L B, Gates M A, Steindler D A
Department of Anatomy and Neurobiology, College of Medicine, University of Tennessee, Memphis 38163, USA.
Glia. 1996 May;17(1):1-14. doi: 10.1002/(SICI)1098-1136(199605)17:1<1::AID-GLIA1>3.0.CO;2-7.
The subependymal zone (SEZ) of the lateral ventricle of adult rodents has long been known to be mitotically active. There has been increased interest in the SEZ, since it has been demonstrated that neuroepithelial stem cells residing there generate neurons in addition to glia in vitro. In the present study, we have examined parasagittal sections of the adult mouse brain using immunocytochemistry for extracellular matrix (ECM) molecules (tenascin and chondroitin sulfate-containing proteoglycans), glial fibrillary acidic protein (GFAP, a cytoskeletal protein prominently expressed by immature and reactive astrocytes), RC-2 (a radial glial and immature astrocyte cytoskeletal marker), TuJ1 (a class III beta-tubulin isoform expressed solely by postmitotic and adult neurons), nestin (a cytoskeletal protein associated with stem cells), neuron-specific enolase, and bromodeoxyuridine (BrdU, which is taken up by dividing cells). Our results demonstrate that a population of young neurons reside within an ECM-rich, GFAP-positive astrocyte pathway from the rostral SEZ all the way into the olfactory bulb. Furthermore, BrdU labeling studies indicate that there is a high level of cell division along the entire length of this path, and double-labeling studies indicate that neurons committed to a neuronal lineage (i.e., TuJ1+) take up BrdU (suggesting they are in the DNA synthesis phase of the cell cycle), again along the entire length of the SEZ "migratory pathway." Thus, the SEZ appears to retain the ability to produce neurons and glia throughout the life of the animal, functioning as a type of "brain marrow." The implications of these findings are discussed in relation to the role that such a glial/ ECM-rich boundary (as seen in the embryonic cortical subplate and other developing areas) may play in: confining the migratory populations and maintaining them in a persistent state of immaturity; facilitating their migration to the olfactory bulb, where they are incorporated into established adult circuitries; and potentially altering SEZ cell cycle dynamics that eventually lead to cell death.
长期以来，人们一直知道成年啮齿动物侧脑室的室管膜下区（SEZ）有活跃的有丝分裂。由于已证明驻留在那里的神经上皮干细胞在体外除了产生神经胶质细胞外还能产生神经元，因此对SEZ的兴趣与日俱增。在本研究中，我们使用免疫细胞化学方法，检测了成年小鼠脑矢状旁切片中的细胞外基质（ECM）分子（腱生蛋白和含硫酸软骨素的蛋白聚糖）、胶质纤维酸性蛋白（GFAP，一种由未成熟和反应性星形胶质细胞显著表达的细胞骨架蛋白）、RC-2（一种放射状胶质细胞和未成熟星形胶质细胞的细胞骨架标记物）、TuJ1（一种仅由有丝分裂后和成年神经元表达的III类β-微管蛋白亚型）、巢蛋白（一种与干细胞相关的细胞骨架蛋白）、神经元特异性烯醇化酶以及溴脱氧尿苷（BrdU，分裂细胞摄取的物质）。我们的结果表明，一群年轻神经元存在于一条富含ECM、GFAP阳性的星形胶质细胞通路中，这条通路从吻侧SEZ一直延伸到嗅球。此外，BrdU标记研究表明，沿着这条通路的全长都有高水平的细胞分裂，双标记研究表明，进入神经元谱系的神经元（即TuJ1+）摄取BrdU（表明它们处于细胞周期的DNA合成阶段），同样沿着SEZ“迁移通路”的全长。因此，SEZ似乎在动物的整个生命过程中都保留着产生神经元和神经胶质细胞的能力，起到一种“脑骨髓”的作用。我们结合这样一个富含胶质/ECM的边界（如在胚胎皮质板下区和其他发育区域所见）可能在以下方面发挥的作用，讨论了这些发现的意义：限制迁移群体并使其保持在持续未成熟状态；促进它们迁移到嗅球，在那里它们被纳入已建立的成年神经回路；以及潜在地改变SEZ细胞周期动力学，最终导致细胞死亡。
