Tau accumulation in astrocytes of the dentate gyrus induces neuronal dysfunction and memory deficits in Alzheimer’s disease
Authors: Enea Parietti
Nicolas Toni
Nicole Déglon
Sabiha Eddarkaoui
Maria Rey
Luc Buée
Kevin Richetin
Sophie Halliez
Mathischan Maheswaran
Geneviève Leuba
Romain Perbet
Pascal Steullet
Kim Q Do
Séverine Bégard
Mathieu Pachoud
Catherine Pythoud
Paola Bezzi
Raphaëlle Caillierez
Morvane Colin
Journal: Nature Neuroscience (2020)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Alzheimer's disease; tau protein; astrocytes; dentate gyrus; neurodegeneration
Affiliations: Department of Psychiatry, Center for Psychiatric Neurosciences, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland. ., Laboratory of Neurotherapies and Neuromodulation, Neuroscience Research Center (CRN), Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland. ., Department of Clinical Neuroscience (DNC), Laboratory of Neurotherapies and Neuromodulation, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland. ., Department of Psychiatry, Center for Psychiatric Neurosciences, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland., Laboratory of Neurotherapies and Neuromodulation, Neuroscience Research Center (CRN), Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland., Department of Clinical Neuroscience (DNC), Laboratory of Neurotherapies and Neuromodulation, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland., Univ. Lille, Inserm, CHU Lille, U1172 - LilNCog - Lille Neuroscience & Cognition, Lille, France., Department of Fundamental Neurosciences, University of Lausanne, Lausanne, Switzerland.

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. 

Retracted: No

PubPeer comments:
 The authors wrote  LV-G1-1N3R-injected mice showed similar performances to control mice in the learning phase and the probe test (Fig. 7eu2013g). However, they showed a deficit in reversal memory (Fig. 7h,i), indicating a difficulty to suppress old spatial memory. But there is NO reversal memory data (which is what you get when you run a probe trial after reversal training. The statement of  reversal memory deficit is entirely based on ONE day (day 3 of reversal) of reversal LEARNING data. Are there no probe trial data after reversal? Why? Also, line graphs and bar graphs are not  histograms . Fig 7g is not Number of crossings -- legend is wrong. , 
 Figure 3h and Supplementary Figure 2: I m a bit confused here. The gel in Fig. 3h doesn t seem to be the same one shown in supplementary Figure 2. The ladder looks different, but even if it is the same, the labelling doesn t make sense. Which lanes exactly are shown? I can t find the bands in Figure 3h in Supplementary Figure 2... Would the authors please comment? ![file] ,