Skip to Main content Skip to Navigation
Journal articles

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

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.
Document type :
Journal articles
Complete list of metadata

https://www.hal.inserm.fr/inserm-03366740
Contributor : Luc BUEE Connect in order to contact the contributor
Submitted on : Tuesday, October 5, 2021 - 5:53:04 PM
Last modification on : Thursday, September 1, 2022 - 8:44:06 AM
Long-term archiving on: : Thursday, January 6, 2022 - 8:22:17 PM

File

 Restricted access
To satisfy the distribution rights of the publisher, the document is embargoed until : jamais

Please log in to resquest access to the document

Identifiers

Collections

Citation

Kevin Richetin, Pascal Steullet, Mathieu Pachoud, Romain Perbet, Enea Parietti, et al.. Tau accumulation in astrocytes of the dentate gyrus induces neuronal dysfunction and memory deficits in Alzheimer’s disease. Nature Neuroscience, Nature Publishing Group, 2020, 23 (12), pp.1567-1579. ⟨10.1038/s41593-020-00728-x⟩. ⟨inserm-03366740⟩

Share

Metrics

Record views

12