​

​
​ E-MAIL   Carole Escartin	​

Reactive astrocytes

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 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 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 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 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 diseases
Finally, 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 diseases.

Virus-mediated expression of SOCS3 in astrocytes in an AD mouse model (3xTg) blunts astrocyte reaction and restores synaptic long term potentiation, a form of synaptic plasticity. Ceyzériat et al., 2018. In collaboration with A. Panatier.

Grants and Awards