Ueki Takatoshi, Tanaka Masamitsu, Yamashita Kanna, Mikawa Sumiko, Qiu ZheFu, Maragakis Nicholas J, Hevner Robert F, Miura Naoyuki, Sugimura Haruhiko, Sato Kohji
Department of Anatomy and Neuroscience, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan.
J Neurosci. 2003 Dec 17;23(37):11732-40. doi: 10.1523/JNEUROSCI.23-37-11732.2003.
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.
神经发生在成年哺乳动物大脑的特定区域，其中海马齿状回中的神经发生在学习和记忆中起着关键作用。迄今为止，人们对导致神经源性区域神经干细胞神经元命运决定的神经源性信号了解甚少，尤其是成年海马神经发生中的神经源性信号。在本研究中，我们发现海马星形胶质细胞以及与神经干细胞相邻的齿状颗粒细胞分泌一种新克隆的新型分泌因子——神经生成素-1。该蛋白包含三个富含半胱氨酸的结构域和一个独特序列，通过阻止神经干细胞向胶质细胞命运转变，促进成年大脑中神经干细胞的神经元分化。此外，抗神经生成素-1抗体的给药显著抑制了海马培养基中检测到的神经源性活性。这些发现揭示了诱导成年海马神经发生的内源性机制，并为导致海马神经元丧失的神经退行性疾病提出了一种创新治疗方法。
