Tau在星形膠質細胞中積累誘發AD

Tau在星形膠質細胞中積累誘發AD

作者：

小柯機器人

發布時間：2020/11/10 22:20:40

瑞士洛桑大學醫院（CHUV）和洛桑大學精神病學神經科學中心Nicolas Toni、Kevin Richetin研究組合作取得最新進展。他們提出Tau在齒狀回星形膠質細胞中的積累會誘發阿爾茨海默氏病（AD）的神經元功能障礙和記憶力減退。該研究於2020年11月9日發表於國際一流學術期刊《自然-神經科學》。

他們發現tau在AD個體齒狀回的肺門星形膠質細胞中積累。在小鼠中，在齒狀回的肺門星形膠質細胞中3R tau的過度表達改變了線粒體的動力學和功能。反過來，這些變化導致成人神經發生，表達小白蛋白的神經元、抑制性突觸和肺門伽馬振蕩的減少，並伴有空間記憶性能的下降。

總之，這些結果表明，齒狀回的肺門星形膠質細胞中tau穩態的喪失足以通過神經元網絡的損傷而誘發AD樣症狀。這些結果對人們理解疾病機制很重要，並強調了星形膠質細胞在海馬功能中的關鍵作用。

據介紹，AD的特徵是tau蛋白在神經元中積、神經變性和記憶喪失。然而，非神經元細胞在這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