TNFα and IL-1β modify the miRNA cargo of astrocyte shed extracellular vesicles to regulate neurotrophic signaling in neurons article

Amrita Datta Chaudhuri, Raha M. Dastgheyb, Seung Wan Yoo, Amanda Trout, C. Conover Talbot, Haiping Hao, Kenneth W. Witwer, Norman J. Haughey

Research output: Contribution to journalArticlepeer-review

101 Scopus citations


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.

Original languageEnglish
Article number363
JournalCell Death and Disease
Issue number3
StatePublished - Mar 1 2018

Bibliographical note

Funding Information:
We would like to thank Saja Khuder for culturing neurons on MEA plates and Anita Cooke for assistance with neurite length measurements using neurolucida. This work was supported by the National Institutes of Health awards: AG057420, DA04039, MH077542, MH075673, and MH110246 to NJH.

Publisher Copyright:
© 2018 The Author(s).

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research


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