Normally, astrocytes play a vital role within the brain, where they support the correct function of neurons. However, in the presence of neurodegenerative pathologies such as Alzheimer's disease, they change into a "reactive" state. What effect does this change have on the astrocyte's normal role of neuronal function support? Are reactive astrocytes beneficial or detrimental in the setting of Alzheimer's disease?
To respond to these questions, researchers from MIRCen1 developed an original, viral-vector-based methodology to block an astrocyte reactivity signaling pathway in a mouse model of Alzheimer's disease. Through partnerships with several French laboratories2, including two at the François Jacob Institute of Biology3, a variety of genetic, histological, biochemical, electrophysiological and behavioral techniques were deployed to determine the consequences of astrocyte reactivity inhibition on the molecular, cellular and functional alterations characteristic of Alzheimer's disease.
This multidisciplinary effort showed that in the setting of Alzheimer's disease, the overall effect of reactive astrocytes was deleterious. By selectively blocking them, the fundamental characteristics of the disease were improved: amyloid deposits were reduced, spatial learning improved and cognitive deficits restored. These results suggest that targeting reactive astrocytes in Alzheimer's disease may be a novel therapeutic strategy with strong potential to improve neuronal function.
1-Molecular Imaging Research Center, Institut de Biologie François Jacob, CEA
2-Neurocentre Magendie, INSERM et Université de Bordeaux
3-IRCM (Research Institute for Cellular and Molecular Radiobiology, Fontenay-aux-Roses) and CNRGH (National Center of Human Genomics Research, Évry).