Neuronal tau species transfer to astrocytes and induce their loss according to tau aggregation state

Anastasie Maté de Gérando; Marie D’orange; Emma Augustin; Charlène Joséphine; Gwénaelle Aurégan; Mylène Gaudin-Guérif; Martine Guillermier; Anne-Sophie Hérard; Lev Stimmer; Fanny Petit; Pauline Gipchtein; Caroline Jan; Carole Escartin; Erwan Selingue; Kévin Carvalho; David Blum; Emmanuel Brouillet; Philippe Hantraye; Marie-Claude Gaillard; Gilles Bonvento; Alexis-Pierre Bemelmans; Karine Cambon

doi:10.3389/fneur.2021.654850

Journal articles

Neuronal tau species transfer to astrocytes and induce their loss according to tau aggregation state

Anastasie Maté de Gérando ¹ Marie D’orange ¹ Emma Augustin ¹ Charlène Joséphine ¹ Gwénaelle Aurégan ¹ Mylène Gaudin-Guérif ¹ Martine Guillermier ¹ Anne-Sophie Hérard ¹ Lev Stimmer ² Fanny Petit ¹ Pauline Gipchtein ¹ Caroline Jan ¹ Carole Escartin ¹ Erwan Selingue ³ Kévin Carvalho ^{4, 5} David Blum ^{4, 5} Emmanuel Brouillet ¹ Philippe Hantraye ¹ Marie-Claude Gaillard ¹ Gilles Bonvento ¹ Alexis-Pierre Bemelmans ¹ Karine Cambon ¹

1 MIRCEN - Service MIRCEN

2 U 1169 - Thérapie génique, Génomique et Epigénomique

3 NEUROSPIN - Service NEUROSPIN

4 LilNCog (ex-JPARC) - Lille Neurosciences & Cognition - U 1172

5 Excellence Laboratory LabEx DISTALZ

Abstract : Deposits of different abnormal forms of tau in neurons and astrocytes represent key anatomo-pathological features of tauopathies. Although tau protein is highly enriched in neurons and poorly expressed by astrocytes, the origin of astrocytic tau is still elusive. Here, we used innovative gene transfer tools to model tauopathies in adult mouse brains and to investigate the origin of astrocytic tau. We showed in our adeno-associated virus (AAV)-based models and in Thy-Tau22 transgenic mice that astrocytic tau pathology can emerge secondarily to neuronal pathology. By designing an in vivo reporter system, we further demonstrated bidirectional exchanges of tau species between neurons and astrocytes. We then determined the consequences of tau accumulation in astrocytes on their survival in models displaying various status of tau aggregation. Using stereological counting of astrocytes, we report that, as for neurons, soluble tau species are highly toxic to some subpopulations of astrocytes in the hippocampus, whereas the accumulation of tau aggregates does not affect their survival. Thus, astrocytes are not mere bystanders of neuronal pathology. Our results strongly suggest that tau pathology in astrocytes may significantly contribute to clinical symptoms.

Keywords : Thy-Tau22 design-based stereology gene-transfer glia tau

Document type :

Journal articles

Domain :

Life Sciences [q-bio] / Neurons and Cognition [q-bio.NC] / Neurobiology

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https://www.hal.inserm.fr/inserm-03385148
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Submitted on : Tuesday, October 19, 2021 - 1:36:55 PM
Last modification on : Monday, December 13, 2021 - 9:16:53 AM

Neuronal tau species transfer to astrocytes and induce their loss according to tau aggregation state

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Neuronal tau species transfer to astrocytes and induce their loss according to tau aggregation state

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