Breakdown of axonal synaptic vesicle precursor transport by microglial
nitric oxide
J Neurosci, 25 (2):
352-62 (January 2005)Stagi, Massimiliano Dittrich, Petra S Frank, Nadja Iliev, Asparouh
I Schwille, Petra Neumann, Harald Research Support, Non-U.S. Gov't
United States The Journal of neuroscience : the official journal
of the Society for Neuroscience J Neurosci. 2005 Jan 12;25(2):352-62..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 NH2-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.