QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, January 12, 2005, 25(2):352-362; doi:10.1523/JNEUROSCI.3887-04.2005

This Article Full Text Full Text (PDF) Supplemental data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (12) Citing Articles via Google Scholar Google Scholar Articles by Stagi, M. Articles by Neumann, H. Search for Related Content PubMed PubMed Citation Articles by Stagi, M. Articles by Neumann, H.

 Previous Article  |  Next Article 

Cellular/Molecular
Breakdown of Axonal Synaptic Vesicle Precursor Transport by Microglial Nitric Oxide

Massimiliano Stagi,^1,2 Petra S. Dittrich,³ Nadja Frank,¹ Asparouh I. Iliev,¹ Petra Schwille,³ and Harald Neumann^1,2

¹Neuroimmunology Group, European Neuroscience Institute Göttingen, 37073 Göttingen, Germany, ²Institute of Multiple Sclerosis Research, University Göttingen and Hertie-Foundation, 37073 Göttingen, Germany, and ³Experimental Biophysics Group, Max-Planck Institute of Biophysical Chemistry, 37077 Göttingen, Germany

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.

Key words: axonal transport; axoplasmic transport; immunity; macrophage; microglia; multiple sclerosis; synaptic

---

Received Sep 20, 2004; revised November 8, 2004; accepted November 16, 2004.

This article has been cited by other articles:

				A. Bosco, D. M. Inman, M. R. Steele, G. Wu, I. Soto, N. Marsh-Armstrong, W. C. Hubbard, D. J. Calkins, P. J. Horner, and M. L. Vetter Reduced Retina Microglial Activation and Improved Optic Nerve Integrity with Minocycline Treatment in the DBA/2J Mouse Model of Glaucoma Invest. Ophthalmol. Vis. Sci., April 1, 2008; 49(4): 1437 - 1446. [Abstract] [Full Text] [PDF]

				M. Makwana, L. L. Jones, D. Cuthill, H. Heuer, M. Bohatschek, M. Hristova, S. Friedrichsen, I. Ormsby, D. Bueringer, A. Koppius, et al. Endogenous Transforming Growth Factor {beta}1 Suppresses Inflammation and Promotes Survival in Adult CNS J. Neurosci., October 17, 2007; 27(42): 11201 - 11213. [Abstract] [Full Text] [PDF]

				M. Stagi, P. Gorlovoy, S. Larionov, K. Takahashi, and H. Neumann Unloading kinesin transported cargoes from the tubulin track via the inflammatory c-Jun N-terminal kinase pathway FASEB J, December 1, 2006; 20(14): 2573 - 2575. [Abstract] [Full Text] [PDF]

				L. P. Shriver and B. N. Dittel T-Cell-Mediated Disruption of the Neuronal Microtubule Network: Correlation with Early Reversible Axonal Dysfunction in Acute Experimental Autoimmune Encephalomyelitis Am. J. Pathol., September 1, 2006; 169(3): 999 - 1011. [Abstract] [Full Text] [PDF]

				S. Ackerley, P. A. James, A. Kalli, S. French, K. E. Davies, and K. Talbot A mutation in the small heat-shock protein HSPB1 leading to distal hereditary motor neuronopathy disrupts neurofilament assembly and the axonal transport of specific cellular cargoes Hum. Mol. Genet., January 15, 2006; 15(2): 347 - 354. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help