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Astrocyte signaling in neurodegenerative diseases

FRM team

​Group leader  : Carole Escartin

E-MAIL : Carole Escartin

Published on 21 April 2023

Research focus RES

We study astrocytes that are key partners of neurons. Under pathological conditions, such as neurodegenerative diseases, astrocytes undergo reactive changes at the morphological, molecular and functional levels. Given the importance of astrocytes, any change in their functions may have major effects on neurons, which in turn can impact complex behaviors (Ben Haim et al., 2015; Escartin et al., 2019; 2021; Ben Haim & Escartin, 2022).

We develop tools to monitor and manipulate reactive astrocytes, by targeting specific signaling cascades, to understand what these cells do, how they interact with neurons and influence behavioral symptoms.


1. Viral vectors to selectively modulate astrocytes in vivo

We identified the JAK2-STAT3 pathway as a key signaling pathway controlling the reactive state of astrocytes in neurodegenerative diseases (Ben Haim et al., 2015; Ceyzériat et al., 2016, 2018). We have developed viral vectors to target this pathway in vivo, to manipulate astrocyte reactive state. In combination with new viral-based reporters and chemogenetic constructs, we now aim to:

  • Understand what reactive astrocytes do in specific disease contexts, using fluorescent-activated cell sorting of astrocytes, transcriptomics, functional and histological analysis as well as behavioral assessment (Part 2).
  • Assess whether reactive astrocytes can be monitored using non-invasive brain imaging techniques to serve as biomarkers for neurological diseases (Part 3).
  • Implement alternative therapeutic strategies for brain diseases by targeting specific populations of reactive astrocytes (Part 4).

Reactive astrocytes overexpressing GFAP (red) in a mouse model of Alzheimer's disease. They display an accumulation
of STAT3 (green) in their nucleus (labeled in blue with DAPI). Ben Haim et al., 2015.


2. Molecular and functional changes in reactive astrocytes in vivo

Our earlier in vivo studies of reactive astrocytes induced by the cytokine CNTF, revealed significant changes in several astrocyte functions (Escartin et al., 2006, 2007). We later showed that reactive astrocytes alter synaptic transmission and plasticity in the mouse hippocampus (Ceyzériat et al., 2018), which could impact complex behaviors including anxiety and sociability. Recently, we showed that STAT3-dependent reactive astrocytes promote proteostasis in Huntington's disease models (Abjean et al., 2023). We are now exploring the molecular and functional heterogeneity of reactive astrocytes, depending on their specific signaling. We are also implementing multi-omics analysis of reactive astrocytes in brain diseases, contributing with a biologist-friendly app for -omic data visualization and analysis (Riquelme-Perez et al., 2022).  

Virus-mediated expression of  SOCS3 in astrocytes inhibits the JAK-STAT3 pathway and normalizes astrocyte transcriptome  in an AD mouse model (APP),  as evidenced by RNAseq on acutely sorted astrocytes. 
Ceyzériat et al., 2018. In collaboration with CNRGH, Evry.

 3. Reactive astrocytes as biomarkers for pathological situations 

Since reactive astrocytes appear under pathological conditions, they could be used as biomarkers for brain diseases. In collaboration with brain imaging teams in MIRCen, we showed that reactive astrocytes are detected by positron emission tomography (PET) using radiotracers for TSPO, a protein previously described as a reactive microglia marker (Lavisse et al., 2012).

TSPO-PET evidences reactive astrocytes in the rat brain (arrowhead in A), as confirmed by specific GFAP immunostaining 
of these cells (arrowhead in B). Lavisse et al., 2012.


4. Reactive astrocytes as therapeutic targets for neurodegenerative diseases

We assess how reactive astrocytes impact multiple disease outcomes in mouse models of brain diseases. We showed that STAT3-dependent reactive astrocytes have beneficial effects in models of Huntington’s disease (Escartin et al.,  2006; Abjean et al., 2023), while they have mainly deleterious effects in Alzheimer’s disease models (Ceyzériat et al., 2018; Guillemaud et al., 2020). We are also investigating whether astrocytes contribute to some neuropsychiatric symptoms observed in neurodegenerative diseases (Ben Haim & Escartin, 2022).

JAK2-STAT3 pathway activation in striatal astrocytes reduces the number of mutant Huntingtin (mHtt) aggregates compared to controls. GluCEST imaging generates glutamate abundance maps and shows better preservation of glutamate levels in the right striatum with JAK2-activated astrocytes. Abjean et al., 2023.

Research focus

Grant & awards




Grants and Awards GA

  • Equipe FRM. 2023-2026. Collaboration with G. Dallerac (NeuroPSI), N. Rouach (Collège de France), E. Bonnet (CNRGH), C. Baligand, M. Dhenain (MIRCen)
  • Fondation Alzheimer. 2023-2025. Coordinated by H. Hirbec (Institut de Génomique Fonctionnelle, Montpellier)
  • France Alzheimer. 2022-2025. Collaboration with N. Rouach (Collège de France)
  • ANR PRC. 2022-2026. Coordinated by E.Nivet (Institut de NeuroPhysiopathologie, Marseille) 
  • Fondation Vaincre Alzheimer. 2021-2022. Pilot Award to L. Ben Haim. 
  • Neuratris. 2021-2023. Collaboration with S. Betuing (Sorbonne Université). 
  • ANR PRC. 2020-2024.Coordinated by S. Betuing (Sorbonne Université)
  • Prix Joël Ménard.  2019 in basic science on Alzheimer’s disease
  • France Alzheimer. 2020-2022. Coordinated by M. Cohen-Salmon (Collège de France) 
  • Fondation Maladies Rares GenOmics. 2019-2020. Collaboration with E. Bonnet (CNRGH, Evry)
  • Neuratris. 2018-2021. Coordinated by F. Ortiz (Univ. Autónoma de Chile) 
  • Association Huntington France. 2018-2019
  • Bronze medal award from CNRS, 2017
  • ANR Tremplin-ERC. 2017-2018
  • Ligue Européenne Contre la Maladie d'Alzheimer, LECMA. 2016-2018 
  • Fédération pour la Recherche sur le Cerveau, FRC. 2016-2018. Collaboration with A. Panatier (Neurocentre Magendie, Bordeaux)
  • ANR Young Investigator grant. 2010-2014

Team members TEAM

  • Carole Escartin. CNRS Research director
  • Lucile Ben Haim. CNRS Researcher (2021-)
  • Maria-Angeles Carrillo-de Sauvage. CNRS Engineer (2015-)
  • Miriam Riquelme Peréz. PhD student. 2019-2023. Multiomics analysis of astrocytes in HD
  • Tom Lakomy. PhD student, 2022-2025. Astrocyte regulation of mouse emotional behavior
  • Karouna Bascarane. PhD student, 2022-2025. Tgln3 effects on reactive astrocytes in AD
  • Vivien Letenneur. Engineer. 2022-2024
  • Yiannis Poulot. PhD student. 2021-2024. Astrocyte heterogeneity in AD


Fabien Aubry

Post-doctoral fellows
Lucile Ben Haim
Ludmila Juricek
Maria Angeles Carrillo de Sauvage

PhD students
Juliette Lopez-Hanotte
Océane Guillemaud
Laurene Abjean
Kelly Ceyzériat
Elena Saavedra-Lopez
Lucile Ben Haim

Master students
Anirudh Krishna
Mie Moller-Clausen
Andrea Dubet
Cameron Héry
Raul Pulgar Sepulveda
Thomas Saint-Georges
Marion Delahaye
Ana-Clara Bobadilla

Main collaborations COLL

  • Drs. S. Brohard & E. Bonnet, Centre National de Recherche en Génomique Humaine (CNRGH), Evry
  • Pr. S. Betuing, Paris Sorbonne Université, Paris
  • Dr. Nivet, Institut de NeuroPhysiopathologie, Marseille
  • Dr. M. Cohen-Salmon, Collège de France, Paris
  • Dr. N. Rouach, Collège de France, Paris
  • Dr. H. Hirbec, Institut de Génomique Fonctionnelle, Montpellier

Selection of publications PUB

* equal contribution

Reactive astrocytes promote proteostasis in Huntington's disease through the JAK2-STAT3 pathway
Abjean L, Ben Haim L*, Riquelme-Perez M*, Gipchtein P, Derbois C, Palomares MA, Petit F, Hérard AS, Gaillard MC, Guillermier M, Gaudin-Guérif M, Aurégan G, Sagar N, Héry C, Dufour N, Robil N, Kabani M, Melki R, De la Grange P, Bemelmans AP, Bonvento G, Deleuze JF, Hantraye P, Flament J, Bonnet E, Brohard S, Olaso R, Brouillet E, Carrillo-de Sauvage MA, Escartin C. Brain, 2023, 146, 1:149-166

DEVEA: an interactive shiny application for Differential Expression analysis, data Visualization and Enrichment Analysis of transcriptomics data.
Riquelme-Perez M*, Perez-Sanz F*, Deleuze JF, Escartin C, Bonnet E, Brohard S.

Astrocytes and neuropsychiatric symptoms in neurodegenerative diseases: Exploring the missing links.
Ben Haim L, Escartin C.
Curr Opin Neurobiol. 2021. 72:63-71

Reactive astrocyte nomenclature, definitions, and future directions 
Escartin C*, Galea E*, […77 authors…], Sofroniew MV*, Verkhratsky A*  
Nat Neurosci. 2021. 24 : 312-25

Complex roles for reactive astrocytes in the triple transgenic mouse model of Alzheimer disease. 
Guillemaud O.*, Ceyzériat K.*, Saint-Georges T., Cambon K., Petit F., Ben Haim L., . . . Escartin C.  
Neurobiology of Aging. 2020. 90:135-46

Questions and (some) answers on reactive astrocytes.
Escartin C, Guillemaud O, Carrillo-de Sauvage M.
Glia. 2019. 67(12):2221-47

Modulation of astrocyte reactivity improves functional deficits in mouse models of Alzheimer's disease.
Ceyzériat K, Ben Haim L, Denizot A, Pommier D, Matos M, Guillemaud O, Palomares MA, Abjean L, Petit F, Gipchtein P, Gaillard MC, Guillermier M, Bernier S, Gaudin M, Aurégan G, Joséphine C, Dechamps N, Veran J, Langlais V, Cambon K, Bémelmans A, Baijer J, Bonvento G, Dhenain M, Deleuze JF, Oliet SHR, Brouillet E, Hantraye P, Carrillo de Sauvage MA, Olaso R, Panatier A, Escartin C. 

The JAK/STAT3 pathway is a common inducer of astrocyte reactivity in Alzheimer's and Huntington's disease.
Ben Haim L, Ceyzériat K, Carrillo-de Sauvage M-A, Aubry F, Auregan G, Guillermier M, Ruiz M, Petit F, Houitte D, Faivre E, Vandesquille M, Aron-Badin R, Dhenain M, Déglon N, Hantraye P, Brouillet E, Bonvento G, Escartin C.
J Neurosci. 2015. 35(6):2817-29.

Connexin 30 sets synaptic strength by controlling astroglial synapse invasion.
Pannasch U, Freche D, Dallérac G, Ghézali G, Escartin C, Ezan P, Cohen-Salmon M, Benchenane K, Abudara V, Dufour A, Lübke JH, Déglon N, Knott G, Holcman D, Rouach N.
Nat Neurosci. 2014. 17(4):549-58.

Reactive astrocytes overexpress TSPO and are detected by TSPO PET imaging.
Lavisse S, Guillermier M, Hérard AS, Petit F, Delahaye M, Van Camp N, Ben Haim L, Lebon V, Remy P, Dollé F, Delzescaux T, Bonvento G, Hantraye P, Escartin C.
J. Neurosci. 2012. 32(32):10809-18.

Research focus

Grant & awards