Peripheral blood exosomes pass blood-brain-barrier and induce glial cell activation

Exosomes are involved in intracellular communication and contain proteins, mRNAs, miRNAs, and signaling molecules. Exosomes were shown to act as neuroinflammatory mediators involved in neurodegenerative diseases including Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS). Brain aging has been associated to increased neuroinflammation. In addition, a decreased extracellular vesicle concentration was observed in aging tissues. The specific mechanisms how exosomes and aging are connected are not known yet.

Researchers from Jena University Hospital have shown that peripheral injection had almost no effect on selected gene expression in the liver. However, exosome injection has led to changes in the specific markers of glial cell activation (CD68, Iba1, GFAP). Interestingly, only injection of exosomes isolated from aged mice induced significant activation of astrocyte cells, as shown by increased GFAP expression.

Transcription levels of genes GFAP, TGF-β, CD68, Iba1 known to be involved in glial cell function are significantly changing after introduction of peripheral extracellular vesicles. Exosomes were able to pass blood brain barrier and induce glial cell activation. GFAP known to be a specific astrocyte activation marker was significantly higher expressed after injection of old but not young exosomes, indicating a possible role of exosomes in the mechanisms of brain aging.

Uptake  of  aged  exosomes  by  astrocytes  and  microglia  cells in  vitro 

Primary  mixed  glial  culture containing  astrocytes  and  microglia  was  incubated  with  PKH67-labeled  exosomes  for  1 h.   Cells  were  stained with  anti-Cy5  antibodies  against  GFAP  (astrocytes)  or  Iba1  (microglia),  nuclei  was  counter-stained  with  DAPI. Exosomes are taken up by both cell population but co-localization with microglia cells was more frequent.