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

  • Guillemaud, Océane
  • Ceyzériat, Kelly
  • Saint-Georges, Thomas
  • Cambon, Karine
  • Petit, Fanny
  • Haim, Lucile
  • Carrillo-de Sauvage, Maria-Angeles
  • Guillermier, Martine
  • Bernier, Sueva
  • Herard, Anne-Sophie
  • Joséphine, Charlène
  • Bemelmans, Alexis
  • Brouillet, Emmanuel
  • Hantraye, Philippe
  • Bonvento, Gilles
  • Escartin, Carole
Publication Date
Dec 04, 2019
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In Alzheimer disease (AD), astrocytes undergo complex changes and become reactive. Theconsequences 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 inthe hippocampus of 3xTg-AD mice, an AD model that develops Tau hyperphosphorylation andaggregation in addition to amyloid deposition. JAK2-STAT3 pathway-mediated modulation ofreactive astrocytes in the hippocampus of 3xTg-AD mice, did not significantly influence Tauphosphorylation or amyloid processing and deposition, at early, advanced and terminal stage of thedisease. Interestingly, inhibition of the JAK2-STAT3 pathway in hippocampal astrocytes did notimprove 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 impactbehavioral outcomes without influencing Tau or amyloid pathology.

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