Figure 2

Exosomal cross talk from the periphery and within the central nervous system (CNS). (A) Influence of peripheral inflammation. Inflammation in the periphery can lead to neural cell impairment by virtue of activated monocyte-derived exosomes. Activated monocyte/macrophages traffic across the blood-brain barrier (BBB) at a high frequency and shed exosomes that can harbor pathogenic cellular products including dysregulated miRNAs, mRNAs and proteins as well as microbial by-products. Once internalized by neural cells, exosomes can functionally transfer the neurotoxic cargo to astrocytes and neurons causing neurodysfunction. (B) Normal intercellular communication in the brain mediated by exosomes. The release and uptake of exosomes by various cell types in the brain is part of normal brain communication. Astrocytes release exosomes enriched in heat shock proteins that serve a neuroprotective function during stress conditions. Exosomes shed by microglia, on the other hand, promote neurotransmission by stimulating ceramide and sphingosine syntheses. Oligodendrocyte-derived exosomes offer metabolic support to neurons in response to glutamate activation while neuronal exosomes regulate differentiation of the former.