Astrocyte‐derived factors regulate CNS myelination

Abstract

AbstractThe role that astrocytes play in central nervous system (CNS) myelination is poorly understood. We investigated the contribution of astrocyte‐derived factors to myelination and revealed a substantial overlap in the secretomes of human and rat astrocytes. Using in vitro myelinating co‐cultures of primary retinal ganglion cells and cortical oligodendrocyte precursor cells, we discovered that factors secreted by resting astrocytes, but not reactive astrocytes, facilitated myelination. Soluble brevican emerged as a new enhancer of developmental myelination in vivo, CNS and its absence was linked to remyelination deficits following an immune‐mediated damage in an EAE mouse model. The observed reduction of brevican expression in reactive astrocytes and human MS lesions suggested a potential link to the compromised remyelination characteristic of neurodegenerative diseases. Our findings suggested brevican's role in myelination may be mediated through interactions with binding partners such as contactin‐1 and tenascin‐R. Proteomic analysis of resting versus reactive astrocytes highlighted a shift in protein expression profiles, pinpointing candidates that either facilitate or impede CNS repair, suggesting that depending on their reactivity state, astrocytes play a dual role during myelination.