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-GFP) 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... More
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-GFP) 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.
