The François Jacob Institute of Biology brings together five departments and three services
The last two years in scientific news
Grant & awards
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:
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).
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).
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).
Technicians Fabien Aubry
Selection of publications PUB
* equal contribution
Reactive astrocytes promote proteostasis in Huntington's disease through the JAK2-STAT3 pathwayAbjean 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
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
Questions and (some) answers on reactive astrocytes.Escartin C, Guillemaud O, Carrillo-de Sauvage M.Glia. 2019. 67(12):2221-47
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
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.
CEA is a French government-funded technological research organisation in four main areas: low-carbon energies, defense and security, information technologies and health technologies. A prominent player in the European Research Area, it is involved in setting up collaborative projects with many partners around the world.