Peripheral blood exosomes pass blood-brain-barrier and induce glial cell activation
Open accessPreprint — published as 10.3390/cells11040625
Abstract
Background: 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. Results: Here we 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. Conclusion: 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.
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The engineered exosomes could cross the multiple layers of the blood-brain-barrier and target cancer cells within the brain tissue.
“Importantly, the engineered exosomes could cross the multiple layers of the blood-brain-barrier (BBB) and target cancer cells within the brain tissue (40, 65–68).”
From Potential Therapeutic Effects of Exosomes Packed With a miR-21-Sponge Construct in a Rat Model of Glioblastoma (2019) · cites this paper as [67]
The Discussion states that exosomes can cross the blood-brain barrier and reports that injected peripheral-blood exosomes localized in recipient mice’s brains (page unavailable). It does not show that engineered exosomes crossed multiple BBB layers or targeted cancer cells in brain tissue; the study examined peripheral-blood exosomes and glial activation. (LLM, conf=0.87)
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Monfared, H., Jahangard, Y., Nikkhah, M., Mirnajafi-Zadeh, J., & Mowla, S. J. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00782 · Cited by 123 · see citing works
Wei, X.-B., Jiang, W.-Q., Zeng, J.-H., Huang, L.-Q., Ding, H.-G., Jing, Y.-W., Han, Y.-L., Li, Y.-C., & Chen, S.-L. (2022) · Molecular Neurobiology · doi:10.1007/s12035-022-02738-1 · Cited by 123 · see citing works
- Authors
- Morales-Prieto, D. M., Stojiljkovic, M., Diezel, C., Streicher, P.-E., Röstel, F., Lindner, J., Weis, S., Schmeer, C., & Marz, M.
- Affiliations
- Jena University Hospital (DE)
- Leibniz Institute on Aging - Fritz Lipmann Institute (FLI) (DE)
- Venue
- bioRxiv (Cold Spring Harbor Laboratory)
- Publisher
- openRxiv
- Published
- 2018-11-29
- OpenAlex
- W2902301305
- Cited by
- 12
- References
- 2
- Citations by year
- 2023: 1 · 2022: 4 · 2021: 1 · 2020: 3 · 2019: 3
- Type
- posted content
- Language
- en
- Open access
- green
- doi.org
- Locations
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- exosomes, blood-brain barrier, glial activation, astrocyte activation, brain aging, extracellular vesicles, glial fibrillary acidic protein, CD68, Iba1, TGF-beta, neuroinflammation, aged mice, peripheral injection, neurodegenerative diseases
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