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Identification of a novel mechanism of blood-brain communication during peripheral inflammation via choroid plexus-derived extracellular vesicles

Sriram Balusu (UGent) , Elien Van Wonterghem (UGent) , Riet De Rycke (UGent) , Koen Raemdonck (UGent) , Stephan Stremersch (UGent) , Kris Gevaert (UGent) , Marjana Brkić (UGent) , Delphine Demeestere (UGent) , Valerie Vanhooren (UGent) , An Hendrix (UGent) , et al.
(2016) EMBO MOLECULAR MEDICINE. 8(10). p.1162-1183
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Abstract
Here, we identified release of extracellular vesicles (EVs) by the choroid plexus epithelium (CPE) as a new mechanism of blood-brain communication. Systemic inflammation induced an increase in EVs and associated pro-inflammatory miRNAs, including miR-146a and miR-155, in the CSF. Interestingly, this was associated with an increase in amount of multivesicular bodies (MVBs) and exosomes per MVB in the CPE cells. Additionally, we could mimic this using LPS-stimulated primary CPE cells and choroid plexus explants. These choroid plexus-derived EVs can enter the brain parenchyma and are taken up by astrocytes and microglia, inducing miRNA target repression and inflammatory gene up-regulation. Interestingly, this could be blocked in vivo by intracerebroventricular (icv) injection of an inhibitor of exosome production. Our data show that CPE cells sense and transmit information about the peripheral inflammatory status to the central nervous system (CNS) via the release of EVs into the CSF, which transfer this pro-inflammatory message to recipient brain cells. Additionally, we revealed that blockage of EV secretion decreases brain inflammation, which opens up new avenues to treat systemic inflammatory diseases such as sepsis.
Keywords
ALZHEIMERS-DISEASE, NEURODEGENERATIVE DISEASES, PROTEOMIC ANALYSIS, IMMUNE-RESPONSE, INTERCELLULAR COMMUNICATION, CSF BARRIER, EMERGING ROLES, NERVOUS-SYSTEM, DENDRITIC CELLS, CEREBROSPINAL FLUID INTERFACE, sepsis, extracellular vesicles, exosomes, blood-brain barrier, choroid plexus

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Citation

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Chicago
Balusu, Sriram, Elien Van Wonterghem, Riet De Rycke, Koen Raemdonck, Stephan Stremersch, Kris Gevaert, Marjana Brkić, et al. 2016. “Identification of a Novel Mechanism of Blood-brain Communication During Peripheral Inflammation via Choroid Plexus-derived Extracellular Vesicles.” Embo Molecular Medicine 8 (10): 1162–1183.
APA
Balusu, S., Van Wonterghem, E., De Rycke, R., Raemdonck, K., Stremersch, S., Gevaert, K., Brkić, M., et al. (2016). Identification of a novel mechanism of blood-brain communication during peripheral inflammation via choroid plexus-derived extracellular vesicles. EMBO MOLECULAR MEDICINE, 8(10), 1162–1183.
Vancouver
1.
Balusu S, Van Wonterghem E, De Rycke R, Raemdonck K, Stremersch S, Gevaert K, et al. Identification of a novel mechanism of blood-brain communication during peripheral inflammation via choroid plexus-derived extracellular vesicles. EMBO MOLECULAR MEDICINE. 2016;8(10):1162–83.
MLA
Balusu, Sriram, Elien Van Wonterghem, Riet De Rycke, et al. “Identification of a Novel Mechanism of Blood-brain Communication During Peripheral Inflammation via Choroid Plexus-derived Extracellular Vesicles.” EMBO MOLECULAR MEDICINE 8.10 (2016): 1162–1183. Print.
@article{8167194,
  abstract     = {Here, we identified release of extracellular vesicles (EVs) by the choroid plexus epithelium (CPE) as a new mechanism of blood-brain communication. Systemic inflammation induced an increase in EVs and associated pro-inflammatory miRNAs, including miR-146a and miR-155, in the CSF. Interestingly, this was associated with an increase in amount of multivesicular bodies (MVBs) and exosomes per MVB in the CPE cells. Additionally, we could mimic this using LPS-stimulated primary CPE cells and choroid plexus explants. These choroid plexus-derived EVs can enter the brain parenchyma and are taken up by astrocytes and microglia, inducing miRNA target repression and inflammatory gene up-regulation. Interestingly, this could be blocked in vivo by intracerebroventricular (icv) injection of an inhibitor of exosome production. Our data show that CPE cells sense and transmit information about the peripheral inflammatory status to the central nervous system (CNS) via the release of EVs into the CSF, which transfer this pro-inflammatory message to recipient brain cells. Additionally, we revealed that blockage of EV secretion decreases brain inflammation, which opens up new avenues to treat systemic inflammatory diseases such as sepsis.},
  author       = {Balusu, Sriram and Van Wonterghem, Elien and De Rycke, Riet and Raemdonck, Koen and Stremersch, Stephan and Gevaert, Kris and Brki\'{c}, Marjana and Demeestere, Delphine and Vanhooren, Valerie and Hendrix, An and Libert, Claude and Vandenbroucke, Roosmarijn},
  issn         = {1757-4684},
  journal      = {EMBO MOLECULAR MEDICINE},
  keyword      = {ALZHEIMERS-DISEASE,NEURODEGENERATIVE DISEASES,PROTEOMIC ANALYSIS,IMMUNE-RESPONSE,INTERCELLULAR COMMUNICATION,CSF BARRIER,EMERGING ROLES,NERVOUS-SYSTEM,DENDRITIC CELLS,CEREBROSPINAL FLUID INTERFACE,sepsis,extracellular vesicles,exosomes,blood-brain barrier,choroid plexus},
  language     = {eng},
  number       = {10},
  pages        = {1162--1183},
  title        = {Identification of a novel mechanism of blood-brain communication during peripheral inflammation via choroid plexus-derived extracellular vesicles},
  url          = {http://dx.doi.org/10.15252/emmm.201606271},
  volume       = {8},
  year         = {2016},
}

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