Complex roles for reactive astrocytes in the triple transgenic mouse model of Alzheimer disease

NEUROBIOLOGY OF AGING

卷:90

Article

Guillemaud, Oceane¹  Ceyzeriat, Kelly^1,2,3  Saint-Georges, Thomas¹  Cambon, Karine¹  Petit, Fanny¹  Ben Haim, Lucile¹  Carrillo-de Sauvage, Maria-Angeles¹  Guillermier, Martine¹  Bernier, Sueva¹  Herard, Anne-Sophie¹  Josephine, Charlene¹  Bemelmans, Alexis Pierre¹  Brouillet, Emmanuel¹  Hantraye, Philippe¹  Bonvento, Gilles¹  Escartin, Carole¹ 

[1] Univ Paris Saclay, CNRS, CEA, Lab Malad Neurodegenerat,MIRCen, Fontenay Aux Roses, France

[2] Univ Hosp Geneva, Dept Psychiat, Div Adult Psychiat, Geneva, Switzerland

[3] Univ Geneva, Univ Hosp Geneva, Div Nucl Med, Geneva, Switzerland

关键词: Reactive astrocytes;    Alzheimer disease;    Tau;    JAK-STAT3 pathway;    SOCS3;    Neuroinflammation;   

DOI  :  10.1016/j.neurobiolaging.2020.02.010

来源: Elsevier

【 摘 要 】

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. (C) 2020 Elsevier Inc. All rights reserved.

【 授权许可】

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