Complex roles for reactive astrocytes in the triple transgenic mouse model of Alzheimer disease.
In: ISSN: 0197-4580 ; Neurobiology of Aging ; https://hal-cea.archives-ouvertes.fr/cea-03023752 ; Neurobiology of Aging, 2020, 90, pp.135-146. ⟨10.1016/j.neurobiolaging.2020.02.010⟩, 2020
Online
academicJournal
Zugriff:
International audience ; In Alzheimer disease (AD), astrocytes undergo complex changes and become reactive. The consequences of this reaction are still unclear. To evaluate the net impact of reactive astrocytes in AD, we developed viral vectors targeting astrocytes that either activate or inhibit the Janus kinase-signal transducer and activator of transcription 3 (JAK2-STAT3) pathway, a central cascade controlling astrocyte reaction. We aimed to evaluate whether reactive astrocytes contribute to tau as well as amyloid pathologies in the hippocampus of 3xTg-AD mice, an AD model that develops tau hyper-phosphorylation and amyloid deposition. JAK2-STAT3 pathway-mediated modulation of reactive astrocytes in 25% of the hippocampus of 3xTg-AD mice did not significantly influence tau phosphorylation or amyloid processing and deposition at early, advanced, and terminal disease stage. Interestingly, inhibition of the JAK2-STAT3 pathway in hippocampal astrocytes did not improve spatial memory in the Y maze but it did reduce anxiety in the elevated plus maze. Our unique approach to specifically manipulate reactive astrocytes in situ show they may impact behavioral outcomes without influencing tau or amyloid pathology.
Titel: |
Complex roles for reactive astrocytes in the triple transgenic mouse model of Alzheimer disease.
|
---|---|
Autor/in / Beteiligte Person: | Guillemaud, Océane ; Ceyzériat, Kelly ; Saint-Georges, Thomas ; Cambon, Karine ; Petit, Fanny ; Ben Haim, Lucile ; Carrillo-de Sauvage, Maria-Angeles ; Guillermier, Martine ; Bernier, Sueva ; Herard, Anne-Sophie ; Joséphine, Charlène ; Bémelmans, Alexis Pierre ; Brouillet, Emmanuel ; Hantraye, Philippe ; Bonvento, Gilles ; Escartin, Carole ; Laboratoire des Maladies Neurodégénératives - UMR 9199 (LMN) ; Service MIRCEN (MIRCEN) ; Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-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-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)-Centre National de la Recherche Scientifique (CNRS) |
Link: | |
Zeitschrift: | ISSN: 0197-4580 ; Neurobiology of Aging ; https://hal-cea.archives-ouvertes.fr/cea-03023752 ; Neurobiology of Aging, 2020, 90, pp.135-146. ⟨10.1016/j.neurobiolaging.2020.02.010⟩, 2020 |
Veröffentlichung: | HAL CCSD ; Elsevier, 2020 |
Medientyp: | academicJournal |
DOI: | 10.1016/j.neurobiolaging.2020.02.010 |
Schlagwort: |
|
Sonstiges: |
|