The François Jacob Institute of Biology brings together five departments and three services
The last two years in scientific news
Group leader: Carole Escartin
We study astrocytes that are key partners of neurons. Under pathological conditions, such as neurodegenerative diseases, astrocytes become reactive. This is defined by morphological changes, but the functional consequences remain unclear (Ben Haim et al., 2015; Escartin et al., 2019; 2021). Given the importance of astrocytes for brain homeostasis, any change in their functions may have major effects on neurons, which in turn regulate complex behaviors.
We develop molecular tools to monitor and modulate reactive astrocytes in situ, in order to better understand the roles of these cells, from the cellular to the behavioral level.
1. Viral vectors to selectively modulate astrocyte reactivity in vivoWe 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 and 2018). We have developed viral vectors to target this pathway in astrocytes in vivo to monitor and manipulate their reactive state. In combination with additional viral gene
transfer-based tools, such as reporter and chemogenetic constructs, it is possible to:
2. Molecular and functional changes in reactive astrocytes in vivoOur earlier in vivo studies
of reactive astrocytes induced by the cytokine CNTF, revealed significant
changes in several astrocyte functions (Escartin et al., 2006 and 2007;
Seidel et al., 2015). We further showed that reactive
astrocytes alter synaptic transmission and plasticity in the hippocampus
(Ceyzériat et al., 2018). We are now exploring the molecular and
functional heterogeneity of reactive astrocytes, and implement multi-omics
analysis of reactive glial cells in brain diseases.
3. Reactive astrocytes as biomarkers for pathological situations As 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) with radiotracers for TSPO, a protein previously described as a reactive microglia marker (Lavisse et al., 2012).
4. Reactive astrocytes as therapeutic targets for neurodegenerative diseasesFinally, we assess how reactive astrocytes
impact disease outcomes at the molecular, cellular, functional and
behavioral levels, in mouse models of brain diseases. We show that reactive
astrocytes have beneficial effects in Huntington’s disease (Escartin et al., 2006; Ben Haim et al., 2015; Abjean et al., 2021)
while they have mainly deleterious impacts in Alzheimer’s disease models
(Ceyzériat et al., ; Guillemaud et al., 2020). We are also investigating the role
of astrocytes in neuropsychiatric symptoms associated with neurodegenerative
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. BioRXiv. 2021, In press at Brain
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* co-corresponding authors.
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.
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