A Novel Secretory Factor, Neurogenesin-1, Provides Neurogenic Environmental Cues for Neural Stem Cells in the Adult Hippocampus
A Novel Secretory Factor, Neurogenesin-1, Provides Neurogenic Environmental Cues for Neural Stem Cells in the Adult Hippocampus
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DOI：
10.1523/jneurosci.23-37-11732.2003
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发表时间：
2003-12
期刊：
影响因子：
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通讯作者：
T. Ueki;Masamitsu Tanaka;Kanna Yamashita;S. Mikawa;ZheFu Qiu;N. Maragakis;R. Hevner;N. Miura;H. Sugimura;Kohji Sato
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文献类型：
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作者：
T. Ueki;Masamitsu Tanaka;Kanna Yamashita;S. Mikawa;ZheFu Qiu;N. Maragakis;R. Hevner;N. Miura;H. Sugimura;Kohji Sato
神经发生发生在成年哺乳动物大脑的有限区域，其中海马齿状回的神经发生在学习和记忆中起着至关重要的作用。到目前为止，关于神经源性线索导致神经源性区域的神经干细胞的神经元命运，特别是成年海马神经发生中的神经源性线索，人们知之甚少。在本研究中，我们发现海马星形胶质细胞和神经干细胞附近的齿状颗粒细胞分泌一种新的克隆的新的分泌因子-神经生成素-1。这种蛋白含有三个富含半胱氨酸的结构域和一个独特的序列，通过防止采用神经胶质命运来促进成年大脑中神经干细胞的神经元分化。此外，在海马区培养上清液中检测到的神经发生活性被给予抗神经生成素-1抗体显著抑制。这些发现提示了诱导成年海马神经发生的内源性机制，并提出了一种导致海马神经元丢失的神经退行性疾病的创新治疗方法。
Neurogenesis occurs in restricted regions in the adult mammalian brain, among which the neurogenesis in the hippocampal dentate gyrus plays the crucial role in learning and memory. To date, little is known about neurogenic cues, which result in the neuronal fate adoption of neural stem cells residing in neurogenic regions, especially neurogenic cues in adult hippocampal neurogenesis. In the present study, we show that hippocampal astrocytes and also dentate granule cells adjacent to neural stem cells secrete a newly cloned novel secretory factor, Neurogenesin-1. This protein contains three cysteine-rich domains and a unique sequence and contributes to neuronal differentiation of neural stem cells in the adult brain by preventing the adoption of a glial fate. Furthermore, the neurogenic activity detected in the hippocampal culture medium was markedly suppressed by the administration of an anti-Neurogenesin-1 antibody. These findings suggest endogenous mechanisms that induce adult hippocampal neurogenesis and propose an innovative treatment for the neurodegenerative diseases that cause loss of hippocampal neurons.