Extracellular vesicle-mediated transfer of functional molecules from the periphery to the brain
Dr. Stefan Momma, Neurological Institute (Edinger Institute) Goethe University Hospital Frankfurt am Main, Germany.
Extracellular vesicles (EVs) are emerging as important carriers for intercellular and interspecies communication and have been implicated in many biological processes. However, due to their small size and the difficulties in manipulating them, data on EV biology have thus far been based mainly on in vitro or indirect in vivo evidence. Therefore, the extent and pathogenic role of EV signaling in vivo, particularly with regard to the transfer of functional molecules, remains poorly understood. To overcome some of the major shortcomings in this field, we introduced the Cre-Lox system to establish a method to trace the functional transfer of RNA or protein by EVs in vivo. We showed that the expression of Cre recombinase in blood cells and bacteria leads to the release of EVs containing Cre mRNA and proteins, respectively. As a result, in mice with a Cre reporter background, the uptake of Cre-containing EVs leads to an irreversible induction of marker gene expression. This allowed us to identify a novel route of communication between the immune system, gut bacteria, and the brain, crossing the intestinal epithelial and blood-brain barriers.