Breakdown of axonal synaptic vesicle precursor transport by microglial nitric oxide

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Massimiliano Stagi - (Author)
  • Petra S. Dittrich - (Author)
  • Nadja Frank - (Author)
  • Asparouh I. Iliev - (Author)
  • Petra Schwille - , Chair of Biophysics (Author)
  • Harald Neumann - (Author)

Abstract

The mechanism of axonal injury in inflammatory brain diseases is still unclear. Increased microglial production of nitric oxide (NO) is a common early sign in neuroinflammatory diseases. We found by fluorescence correlation spectroscopy that synaptophysin tagged with enhanced green fluorescence protein (synaptophysin-EGFP) moves anterogradely in axons of cultured neurons. Activated microglia focally inhibited the axonal movement of synaptophysin-EGFP in a NO synthase-dependent manner. Direct application of a NO donor to neurons resulted in inhibition of axonal transport of synaptophysin-EGFP and synaptotagmin I tagged with EGFP, mediated via phosphorylation of c-jun NH(2)-terminal kinase (JNK). Thus, overt production of reactive NO by activated microglia blocks the axonal transport of synaptic vesicle precursors via phosphorylation of JNK and could cause axonal and synaptic dysfunction.

Details

Original languageEnglish
Pages (from-to)352-362
Number of pages11
JournalJournal of Neuroscience
Volume25
Issue number2
Publication statusPublished - 12 Jan 2005
Peer-reviewedYes

External IDs

PubMed 15647478

Keywords

ASJC Scopus subject areas

Keywords

  • Axonal transport, Axoplasmic transport, Immunity, Macrophage, Microglia, Multiple sclerosis, Synaptic