Complex roles for reactive astrocytes in the triple transgenic mouse model of Alzheimer disease
| Autor: | Martine Guillermier, Carole Escartin, Océane Guillemaud, Alexis-Pierre Bemelmans, Charlène Joséphine, Gilles Bonvento, Emmanuel Brouillet, Kelly Ceyzériat, Thomas Saint-Georges, Philippe Hantraye, Maria-Angeles Carrillo-de Sauvage, Karine Cambon, Sueva Bernier, Fanny Petit, Lucile Ben Haim, Anne-Sophie Hérard |
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| Přispěvatelé: | Laboratoire des Maladies Neurodégénératives - UMR 9199 (LMN), Centre National de la Recherche Scientifique (CNRS)-Service MIRCEN (MIRCEN), Université Paris-Saclay-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-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), Service MIRCEN (MIRCEN), ANR-16-TERC-0016,DecodAstro,Decoder la complexité de la réactivité astrocytaire dans les maladies neurodégénératives(2016), 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-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) |
| Rok vydání: | 2020 |
| Předmět: |
MESH: Signal Transduction
0301 basic medicine Aging MESH: Hippocampus JAK-STAT3 pathway [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology Hippocampus Hippocampal formation MESH: Janus Kinase 2 0302 clinical medicine Neuroinflammation MESH: Animals SOCS3 Phosphorylation 0303 health sciences Chemistry General Neuroscience MESH: STAT3 Transcription Factor MESH: tau Proteins 3. Good health medicine.anatomical_structure Alzheimer disease Alzheimer's disease Signal Transduction Astrocyte STAT3 Transcription Factor Genetically modified mouse Elevated plus maze Amyloid MESH: Mice Transgenic Amyloidogenic Proteins Mice Transgenic tau Proteins Viral vector 03 medical and health sciences medicine Animals 030304 developmental biology MESH: Amyloidogenic Proteins MESH: Phosphorylation Activator (genetics) Janus Kinase 2 medicine.disease MESH: Astrocytes Disease Models Animal 030104 developmental biology Astrocytes Reactive astrocytes Neurology (clinical) Tau MESH: Disease Models Animal Geriatrics and Gerontology Neuroscience MESH: Alzheimer Disease 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Neurobiology of Aging Neurobiology of Aging, Elsevier, 2020, 90, pp.135-146. ⟨10.1016/j.neurobiolaging.2020.02.010⟩ Neurobiology of Aging, 2020, 90, pp.135-146. ⟨10.1016/j.neurobiolaging.2020.02.010⟩ |
| ISSN: | 0197-4580 |
| Popis: | 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 recently developed viral vectors targeting astrocytes that either activate or inhibit the 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 hyperphosphorylation and aggregation in addition to amyloid deposition. JAK2-STAT3 pathway-mediated modulation of reactive astrocytes in the hippocampus of 3xTg-AD mice, did not significantly influence Tau phosphorylation or amyloid processing and deposition, at early, advanced and terminal stage of the disease. Interestingly, inhibition of the JAK2-STAT3 pathway in hippocampal astrocytes did not improve short-term spatial memory in the Y maze but it reduced anxiety in the elevated plus maze. Our unique approach to specifically manipulate reactive astrocytes in situ show these cells may impact behavioral outcomes without influencing Tau or amyloid pathology. |
| Databáze: | OpenAIRE |
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