Givogri Maria I, de Planell Maria, Galbiati Francesca, Superchi Daniela, Gritti Angela, Vescovi Angelo, de Vellis Jean, Bongarzone Ernesto R
Laboratory for Gene Therapy of Neurodegenerative Disorders, San Raffaele Telethon Institute for Gene Therapy, Milan, Italy.
Dev Neurosci. 2006;28(1-2):81-91. doi: 10.1159/000090755.
The postnatal subventricular zone (SVZ) is a niche for continuous neurogenesis in the adult brain and likely plays a fundamental role in self-repair responses in neurodegenerative conditions. Maintenance of the pool of neural stem cells within this area depends on cell-cell communication such as that provided by the Notch signaling pathway. Notch1 receptor mRNA has been found distributed in different areas of the postnatal brain including the SVZ. Although the identity of Notch1-expressing cells has been established in the majority of these areas, it is still unclear what cell types within the SVZ are expressing components of this pathway. Here we demonstrate that most of expression of Notch1 in the adult SVZ occurs in polysialylated neural cell adhesion molecule (PSA-NCAM)-positive neural precursors and in glial fibrillary acidic protein-positive SVZ astrocytes. Notch1 was also found in PSA-NCAM-positive neuroblasts located within the rostral migratory stream (RMS) but much less in those that have reached the olfactory bulb. We show that two of the naturally occurring Notch1 activators, Jagged1 and Delta1, are also expressed in the SVZ and within the RMS in the adult mouse brain. Finally, using a model of cortical stab wound, we show that the astrogliogenic response of the SVZ to injury is accompanied by activation of the Notch pathway.
产后脑室下区（SVZ）是成人大脑中持续神经发生的微环境，可能在神经退行性疾病的自我修复反应中发挥重要作用。该区域内神经干细胞池的维持依赖于细胞间通讯，如Notch信号通路所提供的通讯。已发现Notch1受体mRNA分布于产后大脑的不同区域，包括SVZ。尽管在这些区域的大多数中，表达Notch1的细胞身份已确定，但尚不清楚SVZ内哪些细胞类型表达该信号通路的组成成分。在这里，我们证明，成体SVZ中Notch1的大部分表达发生在多唾液酸神经细胞黏附分子（PSA-NCAM）阳性的神经前体细胞和胶质纤维酸性蛋白阳性的SVZ星形胶质细胞中。在位于吻侧迁移流（RMS）中的PSA-NCAM阳性神经母细胞中也发现了Notch1，但在到达嗅球的神经母细胞中含量要少得多。我们表明，两种天然存在的Notch1激活剂Jagged1和Delta1也在成年小鼠大脑的SVZ和RMS中表达。最后，使用皮质刺伤模型，我们表明SVZ对损伤的星形胶质细胞生成反应伴随着Notch信号通路的激活。
