Regulation of physical microglia–neuron interactions by fractalkine signaling after status epilepticus

Ukpong B. Eyo, Jiyun Peng, Madhuvika Murugan, Mingshu Mo, Almin Lalani, Ping Xie, Pingyi Xu, David J. Margolis, Long Jun Wu

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Microglia, the resident immune cells of the brain, perform elaborate surveillance in which they physically interact with neuronal elements. A novel form of microglia–neuron interaction named microglial process convergence (MPC) toward neuronal axons and dendrites has recently been described. However, the molecular regulators and pathological relevance of MPC have not been explored. Here, using high-resolution two-photon imaging in vivo and ex vivo, we observed a dramatic increase in MPCs after kainic acid– or pilocarpine-induced experimental seizures that was reconstituted after glutamate treatment in slices from mice. Interestingly, a deficiency of the fractalkine receptor (CX3CR1) decreased MPCs, whereas fractalkine (CX3CL1) treatment increased MPCs, suggesting that fractalkine signaling is a critical regulator of these microglia–neuron interactions. Furthermore, we found that interleukin-1β was necessary and sufficient to trigger CX3CR1-dependent MPCs. Finally, we show that a deficiency in fractalkine signaling corresponds with increased seizure phenotypes. Together, our results identify the neuroglial CX3CL1–CX3CR1 communication axis as a modulator of potentially neuroprotective microglia– neuron physical interactions during conditions of neuronal hyperactivity.

Original languageEnglish (US)
Article numbere0209
JournaleNeuro
Volume3
Issue number6
DOIs
StatePublished - Dec 29 2016

Keywords

  • Epilepsy
  • Fractalkine
  • Glutamate
  • Interleukin-1β
  • Microglia
  • Seizure

ASJC Scopus subject areas

  • Neuroscience(all)

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    Eyo, U. B., Peng, J., Murugan, M., Mo, M., Lalani, A., Xie, P., Xu, P., Margolis, D. J., & Wu, L. J. (2016). Regulation of physical microglia–neuron interactions by fractalkine signaling after status epilepticus. eNeuro, 3(6), [e0209]. https://doi.org/10.1523/ENEURO.0209-16.2016