Laboratory of Axon-Glia Interactions
Axons are able to respond to changes in their environment by producing proteins locally. Intra-axonal protein synthesis plays relevant roles in growth cone behavior and synapse formation during embryonic development, and in axon maintenance by regulating mitochondrial function in adulthood. Importantly, a role for local translation in mediating amyloid-induced neurodegeneration, a hallmark for Alzheimer´s disease, has recently been described.
Although most localized mRNAs are believed to be transported to distal axons from the somatodendritic compartment, recent evidence suggests that some axonal transcripts might be delivered to axons by glial cells. Among the mechanisms proposed for this horizontal transfer, is the secretion of RNA-containing extracellular vesicles (EVs) by glia and subsequent internalization into axons. Our aim is to determine the contribution of glial EVs in the ability of axons to translate proteins locally in models of amyloid-induced pathology. Ultimately we wish to understand if EVs play a role in neurological disorders such Alzheimer´s disease, by regulating intra-axonal signaling events that require local translation.
RNA horizontal transfer from glia to axons will be addressed using a culturing devices (e.g. microfluidic chambers) that allow the isolation of axons from their corresponding soma while permitting culturing glia in the axonal compartment (axon-glia co-cultures), treating isolated axons with purified EVs or inducing axon-to-soma degeneration by applying amyloid oligomers to axons alone. EVs release by glia will be analyzed using basic biochemistry techniques, as well as STED microscopy. Finally, RNA-Seq will be used to characterize RNA species present in glial EVs that can be potentially transferred to axons.