Exosomes secreted by cortical neurons upon glutamatergic synapse activation specifically interact with neurons

TLDR

Exosomes are nano‑sized vesicles released by multivesicular bodies that mediate cell‑cell communication in the nervous system, with secretion regulated by glutamate. The study tests whether neuronal exosomes bind specifically to other neurons, supporting a role in interneuronal communication. The authors compared binding specificity of exosomes from neuroblastoma cells and cortical neurons using dissociated hippocampal cultures. Neuroblastoma exosomes bind indiscriminately to neurons and glial cells, whereas exosomes released from stimulated cortical neurons bind exclusively to neurons, indicating selective neuron‑to‑neuron communication.

Abstract

Exosomes are nano-sized vesicles of endocytic origin released into the extracellular space upon fusion of multivesicular bodies with the plasma membrane. Exosomes represent a novel mechanism of cell-cell communication allowing direct transfer of proteins, lipids and RNAs. In the nervous system, both glial and neuronal cells secrete exosomes in a way regulated by glutamate. It has been hypothesized that exosomes can be used for interneuronal communication implying that neuronal exosomes should bind to other neurons with some kind of specificity. Here, dissociated hippocampal cells were used to compare the specificity of binding of exosomes secreted by neuroblastoma cells to that of exosomes secreted by cortical neurons. We found that exosomes from neuroblastoma cells bind indiscriminately to neurons and glial cells and could be endocytosed preferentially by glial cells. In contrast, exosomes secreted from stimulated cortical neurons bound to and were endocytosed only by neurons. Thus, our results demonstrate for the first time that exosomes released upon synaptic activation do not bind to glial cells but selectively to other neurons suggesting that they can underlie a novel aspect of interneuronal communication.