瑞士洛桑大学医院（CHUV）和洛桑大学精神病学神经科学中心Nicolas Toni、Kevin Richetin研究组合作取得最新进展。他们提出Tau在齿状回星形胶质细胞中的积累会诱发阿尔茨海默氏病（AD）的神经元功能障碍和记忆力减退。该研究于2020年11月9日发表于国际一流学术期刊《自然-神经科学》。
他们发现tau在AD个体齿状回的肺门星形胶质细胞中积累。在小鼠中，在齿状回的肺门星形胶质细胞中3R tau的过度表达改变了线粒体的动力学和功能。反过来，这些变化导致成人神经发生，表达小白蛋白的神经元、抑制性突触和肺门伽马振荡的减少，并伴有空间记忆性能的下降。
总之，这些结果表明，齿状回的肺门星形胶质细胞中tau稳态的丧失足以通过神经元网络的损伤而诱发AD样症状。这些结果对人们理解疾病机制很重要，并强调了星形胶质细胞在海马功能中的关键作用。
据介绍，AD的特征是tau蛋白在神经元中积、神经变性和记忆丧失。然而，非神经元细胞在这一系列事件中的作用仍不清楚。
附：英文原文
Title: Tau accumulation in astrocytes of the dentate gyrus induces neuronal dysfunction and memory deficits in Alzheimer’s disease
Author: Kevin Richetin, Pascal Steullet, Mathieu Pachoud, Romain Perbet, Enea Parietti, Mathischan Maheswaran, Sabiha Eddarkaoui, Sverine Bgard, Catherine Pythoud, Maria Rey, Raphalle Caillierez, Kim Q Do, Sophie Halliez, Paola Bezzi, Luc Bue, Genevive Leuba, Morvane Colin, Nicolas Toni, Nicole Dglon
Issue&Volume: 2020-11-09
Abstract: Alzheimer’s disease (AD) is characterized by the accumulation of the tau protein in neurons, neurodegeneration and memory loss. However, the role of non-neuronal cells in this chain of events remains unclear. In the present study, we found accumulation of tau in hilar astrocytes of the dentate gyrus of individuals with AD. In mice, the overexpression of 3R tau specifically in hilar astrocytes of the dentate gyrus altered mitochondrial dynamics and function. In turn, these changes led to a reduction of adult neurogenesis, parvalbumin-expressing neurons, inhibitory synapses and hilar gamma oscillations, which were accompanied by impaired spatial memory performances. Together, these results indicate that the loss of tau homeostasis in hilar astrocytes of the dentate gyrus is sufficient to induce AD-like symptoms, through the impairment of the neuronal network. These results are important for our understanding of disease mechanisms and underline the crucial role of astrocytes in hippocampal function.
DOI: 10.1038/s41593-020-00728-x
Source: https://www.nature.com/articles/s41593-020-00728-x
Nature Neuroscience：《自然—神经科学》，创刊于1998年。隶属于施普林格·自然出版集团，最新IF：28.771
官方网址：https://www.nature.com/neuro/
投稿链接：https://mts-nn.nature.com/cgi-bin/main.plex
本期文章：《自然—神经科学》：Online/在线发表
