Breakdown of Axonal Synaptic Vesicle Precursor Transport by Microglial Nitric Oxide

Overview

Journal J Neurosci

Specialty Neurology

Date 2005 Jan 14

PMID 15647478

Citations 33

Authors

Massimiliano Stagi

Petra S Dittrich

Nadja Frank

Asparouh I Iliev

Petra Schwille

Harald Neumann

Affiliations

Soon will be listed here.

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.

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