Tau accumulation in astrocytes of the dentate gyrus induces neuronal dysfunction and memory deficits in Alzheimer’s disease

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...

Full description

Saved in:

Bibliographic Details
Published in:	Nature neuroscience Vol. 23; no. 12; pp. 1567 - 1579
Main Authors:	Richetin, Kevin, Steullet, Pascal, Pachoud, Mathieu, Perbet, Romain, Parietti, Enea, Maheswaran, Mathischan, Eddarkaoui, Sabiha, Bégard, Séverine, Pythoud, Catherine, Rey, Maria, Caillierez, Raphaëlle, Q Do, Kim, Halliez, Sophie, Bezzi, Paola, Buée, Luc, Leuba, Geneviève, Colin, Morvane, Toni, Nicolas, Déglon, Nicole
Format:	Journal Article
Language:	English
Published:	New York Nature Publishing Group US 01-12-2020 Nature Publishing Group
Subjects:	14/19 42/44 631/378/1595/1554 631/378/1689/1283 631/378/2596/1308 64/60 9/30 96/10 96/35 Accumulation Alzheimer Disease - complications Alzheimer Disease - metabolism Alzheimer Disease - psychology Alzheimer's disease Animal Genetics and Genomics Animals Animals, Genetically Modified Astrocytes Astrocytes - metabolism Behavioral Sciences Biological Techniques Biomedical and Life Sciences Biomedicine Care and treatment Dentate gyrus Dentate Gyrus - metabolism Development and progression Female Gene expression Genetic aspects Health aspects Hippocampus Homeostasis Humans Life Sciences Memory Memory consolidation Memory Disorders - etiology Memory Disorders - metabolism Memory Disorders - psychology Memory tasks Mice Mice, Inbred C57BL Mitochondria Nerve Net - metabolism Neurobiology Neurodegeneration Neurodegenerative diseases Neurogenesis Neurons Neurons and Cognition Neurosciences Oscillations Parvalbumin Parvalbumins - metabolism Pregnancy Proteins Psychomotor Performance Rats Signs and symptoms Spatial analysis Spatial Memory Synapses Synapses - physiology Tau protein Tau proteins tau Proteins - metabolism Switzerland
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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. Alzheimer’s disease is often considered a disease of neurons. This study reveals that astrocytes are also impaired by the disease and that these cells contribute more to memory deterioration than previously thought.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1097-6256 1546-1726
DOI:	10.1038/s41593-020-00728-x