TNFα and IL-1β modify the miRNA cargo of astrocyte shed extracellular vesicles to regulate neurotrophic signaling in neurons
Open accessAbstract
Astrocytes are known to be critical regulators of neuronal function. However, relatively few mediators of astrocyte to neuron communication have been identified. Recent advancements in the biology of extracellular vesicles have begun to implicate astrocyte derived extracellular vesicles (ADEV) as mediators of astrocyte to neuron communication, suggesting that alterations in the release and/or composition of ADEVs could influence gliotransmission. TNFα and IL-1β are key mediators of glial activation and neuronal damage, but the effects of these cytokines on the release or molecular composition of ADEVs is unknown. We found that ADEVs released in response to IL-1β (ADEV-IL-1β) and TNFα (ADEV-TNFα) were enriched with miRNAs that target proteins involved in neurotrophin signaling. We confirmed that miR-125a-5p and miR-16-5p (both enriched in ADEV-IL-1β and ADEV-TNFα) targeted NTKR3 and its downstream effector Bcl2. Downregulation of these targets in neurons was associated with reductions in dendritic growth, dendritic complexity, reduced spike rates, and burst activity. Molecular interference of miR-125a-5p and miR-16-5p prevented ADEV-IL-1β from reducing dendritic complexity, spike, and burst rates. These findings suggest that astrocytes respond to inflammatory challenge by modifying the miRNA cargo of ADEVs to diminish the activity of target neurons by regulating the translational expression of proteins controlling programs essential for synaptic stability and neuronal excitability.
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In the context of TNF-α or IL-1β stimulation, astrocyte-derived EVs contain miR-125a-5p and miR-16-5p.
“Furthermore, in the context of TNF-α or IL-1β stimulation, astrocyte-derived EVs have been shown to contain miR-125a-5p and miR-16-5p [198].”
From Extracellular vesicles as nanotheranostic platforms for targeted neurological disorder interventions (2024) · cites this paper as [198]
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- Authors
- Chaudhuri, A. D., Dastgheyb, R. M., Yoo, S.-W., Trout, A., Talbot Jr, C. C., Hao, H., Witwer, K. W., & Haughey, N. J.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Haughey, Norman J.
- ORCID
- Venue
- Cell Death & Disease
- Published
- 2018-03-05
- Volume
- 9
- Issue
- 3
- Pages
- 363-363
- ISSN
- 2041-4889 (ISSN-L)
- PMC
- PMC5838212
- OpenAlex
- W2789263143
- Cited by
- 184
- References
- 81
- Citations by year
- 2026: 10 · 2025: 15 · 2024: 21 · 2023: 31 · 2022: 31 · 2021: 30 · 2020: 27 · 2019: 15 · 2018: 4
- FWCI
- 7.12
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Cell Death and Disease (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Institutes of Health (DA04039, MH075673)
- National Institute on Aging (R01AG057420)
- National Institute of Mental Health (P01MH105280, R25MH080661, R01MH110246, R01MH077542, P30MH075673)
- National Institute on Drug Abuse (R01DA040385, R01DA040390)
- 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 › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- gliotransmission, astrocyte-neuron communication, TNF-α, IL-1β, microRNA cargo, miR-125a-5p, miR-16-5p, NTRK3, Bcl-2, neurotrophin signaling, dendritic complexity, neuronal excitability, synaptic stability, neuroinflammation, glial activation
- MeSH terms
- Extracellular Vesicles, Animals, Astrocytes, Base Sequence, Dendrites, Humans, Nerve Growth Factors, Nerve Net, Neurons, Tumor Necrosis Factor-alpha, Signal Transduction, Rats, Sprague-Dawley, Receptor, trkC, MicroRNAs, Interleukin-1beta, HEK293 Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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