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.

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1. Viral vectors to selectively modulate astrocytes in vivo

 

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).

 

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.

Grants and Awards GA