Neuronal tau species transfer to astrocytes and induce their loss according to tau aggregation state
| Autor: | Fanny Petit, Erwan Selingue, Charlène Joséphine, Gilles Bonvento, Gwenaëlle Auregan, Anne-Sophie Hérard, Marie D’orange, Emmanuel Brouillet, Carole Escartin, Martine Guillermier, Mylène Gaudin-Guérif, Alexis-Pierre Bemelmans, Pauline Gipchtein, Emma Augustin, Anastasie Maté de Gérando, Karine Cambon, Marie-Claude Gaillard, Philippe Hantraye, Lev Stimmer, Caroline Jan, David Blum, Kevin Carvalho |
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| Přispěvatelé: | Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service MIRCEN (MIRCEN), Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Thérapie génique, Génomique et Epigénomique (U 1169), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Service NEUROSPIN (NEUROSPIN), Excellence Laboratory LabEx DISTALZ, Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Lille Neurosciences & Cognition - U 1172 (LilNCog), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Blum, David |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Genetically modified mouse Tau pathology glia design-based stereology [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology Tau protein Hippocampus tau Proteins Gene transfer Biology Mice Protein Aggregates 03 medical and health sciences gene-transfer 0302 clinical medicine In vivo mental disorders Animals Humans Protein Isoforms tau Neurons [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology 030104 developmental biology Tauopathies Astrocytes % abnormal forms Design based stereology biology.protein Neurology (clinical) Thy-Tau22 Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Brain-A Journal of Neurology Brain-A Journal of Neurology, Oxford University Press (OUP), 2021, ⟨10.1093/brain/awab011⟩ Brain-A Journal of Neurology, Oxford University Press (OUP), 2021, 12 (4), pp.1167-1182. ⟨10.3389/fneur.2021.654850⟩ Brain-A Journal of Neurology, 2021, 12 (4), pp.1167-1182. ⟨10.1093/brain/awab011⟩ |
| ISSN: | 0006-8950 1460-2156 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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