Multiple roles for astrocytes in neurodegenerative diseases

Carole Escartin PhD, HDR
NeuroPSI, Institut des Neurosciences Paris Saclay |UMR 9197|Saclay. France.

Résumé : Astrocytes are key partners for neurons in the brain: beyond their multiple homeostatic functions, they also actively modulate synaptic activity and plasticity, contributing to brain computing.
Under pathological conditions, such as neurodegenerative diseases, astrocytes change and become reactive. Even if this major brain response was described more than hundred years ago, many questions remain about how the reactive state of astrocytes is controlled, and how this impacts their functions and surrounding cells (Escartin, Galea, et al., 2021).
We have developed virus-based tools to modulate and monitor reactive astrocytes in situ, and we show that these cells play key roles in neurodegenerative diseases, in a context-dependent manner. We have identified the JAK2-STAT3 pathway as a key cascade controlling reactive astrocytes, allowing their manipulation in specific brain regions of animal models of brain disease (Ben Haim et al., 2015). We show that STAT3-dependent hippocampal astrocytes have mostly detrimental effects in mouse models Alzheimer’s disease, by promoting amyloid deposition and synaptic alterations (Ceyzeriat et al., 2018; Guillemaud et al., 2020). Unexpectedly, in the context of Huntington’s disease, striatal astrocytes gain beneficial functions instead, by promoting mutant huntingtin clearance through bi-directional communication with neurons (Abjean et al., 2023).
Astrocytes emerge as key elements in brain diseases, with complex, finely regulated functional changes and various impacts on neurons and disease progression. A detailed and extensive characterization of their roles in different disease contexts will help design efficient therapeutic strategies targeting astrocytes.

Invitée par David Robbe

Lundi 7 octobre 2024 à 11h – Salle de conférence de l’Inmed