Exosome reporter mice reveal the involvement of exosomes in mediating neuron to astroglia communication in the CNS

Nat Commun. 2019 Sep 12;10(1):4136. doi: 10.1038/s41467-019-11534-w.


Astroglia play active and diverse roles in modulating neuronal/synaptic functions in the CNS. How these astroglial functions are regulated, especially by neuronal signals, remains largely unknown. Exosomes, a major type of extracellular vesicles (EVs) that originate from endosomal intraluminal vesicles (ILVs), have emerged as a new intercellular communication process. By generating cell-type-specific ILVs/exosome reporter (CD63-GFPf/f) mice and immuno-EM/confocal image analysis, we found that neuronal CD63-GFP+ ILVs are primarily localized in soma and dendrites, but not in axonal terminals in vitro and in vivo. Secreted neuronal exosomes contain a subset of microRNAs (miRs) that is distinct from the miR profile of neurons. These miRs, especially the neuron-specific miR-124-3p, are potentially internalized into astrocytes. MiR-124-3p further up-regulates the predominant glutamate transporter GLT1 by suppressing GLT1-inhibiting miRs. Our findings suggest a previously undescribed neuronal exosomal miR-mediated genetic regulation of astrocyte functions, potentially opening a new frontier in understanding CNS intercellular communication.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / metabolism*
  • Astrocytes / ultrastructure
  • Cell Communication*
  • Central Nervous System / metabolism*
  • Excitatory Amino Acid Transporter 2 / metabolism
  • Exosomes / metabolism*
  • Exosomes / ultrastructure
  • Genes, Reporter*
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Mice, Inbred C57BL
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Models, Biological
  • Neurons / metabolism*
  • Neurons / ultrastructure


  • Excitatory Amino Acid Transporter 2
  • MicroRNAs
  • Mirn124 microRNA, mouse
  • Slc1a2 protein, mouse
  • Green Fluorescent Proteins