Laboratory of Astrocyte Biology and CNS Regeneration, Center for Brain Repair, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
Faculty of Science and Engineering, Biosciences, Åbo Akademi University, Turku, Finland.
Cereb Cortex. 2019 Sep 13;29(10):4050-4066. doi: 10.1093/cercor/bhy284.
The intermediate filament (nanofilament) protein nestin is a marker of neural stem cells, but its role in neurogenesis, including adult neurogenesis, remains unclear. Here, we investigated the role of nestin in neurogenesis in adult nestin-deficient (Nes-/-) mice. We found that the proliferation of Nes-/- neural stem cells was not altered, but neurogenesis in the hippocampal dentate gyrus of Nes-/- mice was increased. Surprisingly, the proneurogenic effect of nestin deficiency was mediated by its function in the astrocyte niche. Through its role in Notch signaling from astrocytes to neural stem cells, nestin negatively regulates neuronal differentiation and survival; however, its expression in neural stem cells is not required for normal neurogenesis. In behavioral studies, nestin deficiency in mice did not affect associative learning but was associated with impaired long-term memory.
中间丝（微丝）蛋白巢蛋白是神经干细胞的标志物，但它在神经发生中的作用，包括成年神经发生，仍不清楚。在这里，我们研究了巢蛋白在成年巢蛋白缺陷（Nes-/-）小鼠神经发生中的作用。我们发现，Nes-/-神经干细胞的增殖没有改变，但Nes-/-小鼠海马齿状回的神经发生增加了。令人惊讶的是，巢蛋白缺陷的促神经发生作用是由其在星形胶质细胞龛中的功能介导的。通过其在星形胶质细胞到神经干细胞的 Notch 信号转导中的作用，巢蛋白负调控神经元分化和存活；然而，其在神经干细胞中的表达对于正常的神经发生不是必需的。在行为研究中，小鼠巢蛋白缺陷并不影响联想学习，但与长期记忆受损有关。
