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Breakdown of axonal synaptic vesicle precursor transport by microglial nitric oxide

被引：58
作者：
Stagi, M
Dittrich, PS
Frank, N
Iliev, AI
Schwille, P
Neumann, H
机构：
[1] European Neurosci Inst Gottingen, Neuroimmunol Grp, D-37073 Gottingen, Germany
[2] Univ Gottingen, Inst Multiple Sclerosis Res, D-37073 Gottingen, Germany
[3] Hertie Fdn, D-37073 Gottingen, Germany
[4] Max Planck Inst Biophys Chem, Expt Biophys Grp, D-37077 Gottingen, Germany
来源：
JOURNAL OF NEUROSCIENCE | 2005年 / 25卷 / 02期
关键词：
axonal transport; axoplasmic transport; immunity; macrophage; microglia; multiple sclerosis; synaptic;
D O I：
10.1523/JNEUROSCI.3887-04.2005
中图分类号：
Q189 [神经科学];
学科分类号：
071006 ;
摘要：
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.
引用
收藏
页码：352 / 362
页数：11
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