| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||
Received April 12, 2002
Accepted after revision June 11, 2002
1 Department of Neuroscience, University of Edinburgh, Edinburgh, EH8 9JZ, UK and Centre for Molecular Medicine (ZMMK) and Institute for Genetics, University of Cologne, Cologne 50674, Germany
2 Centre for Molecular Medicine (ZMMK) and Institute for Genetics, University of Cologne, Cologne 50674, Germany
3 Department of Neuroscience, University of Edinburgh, Edinburgh, EH8 9JZ, UK
4 Department of Neuroscience, University of Edinburgh, 1 George Square, Edinburgh, EH8 9JZ, UK
* To whom correspondence should be addressed. E-mail: rrr{at}ed.ac.uk.
Axons in WldS mutant mice are protected from Wallerian degeneration by overexpression of a chimeric Ube4b/Nmnat (Wld) gene. Expression of Wld protein was independent of age in these mice. However we identified two distinct neuromuscular synaptic responses to axotomy. In young adult Wlds mice, axotomy induced progressive, asynchronous synapse withdrawal from motor endplates, strongly resembling neonatal synapse elimination. Thus, five days after axotomy, 50-90 % of endplates were still partially or fully occupied and expressed endplate potentials (EPPs). By 10 days fewer than 20 % of endplates still showed evidence of synaptic activity. Recordings from partially occupied junctions indicated a progressive decrease in quantal content in inverse proportion to endplate occupancy. In Wlds mice aged > 7 months, axons were still protected from axotomy but synapses degenerated rapidly, in wild-type fashion: within three days less than 5 % of endplates contained vestiges of nerve terminals. The axotomy-induced synaptic withdrawal phenotype decayed with a time constant of ~30 days. Regenerated synapses in mature Wlds mice recapitulated the juvenile phenotype. Within 4-6 days of axotomy 30-50 % of regenerated nerve terminals still occupied motor endplates. Age-dependent synapse withdrawal was also seen in transgenic mice expressing the Wld gene. Co-expression of Wld protein and cyan fluorescent protein (CFP) in axons and neuromuscular synapses did not interfere with the protection from axotomy conferred by the Wld gene. Thus, Wld expression unmasks age-dependent, compartmentally organised programs of synapse withdrawal and degeneration.
This article has been cited by other articles:
|
|
 |
|
  G. R. Howell, R. T. Libby, T. C. Jakobs, R. S. Smith, F. C. Phalan, J. W. Barter, J. M. Barbay, J. K. Marchant, N. Mahesh, V. Porciatti, et al. Axons of retinal ganglion cells are insulted in the optic nerve early in DBA/2J glaucoma J. Cell Biol., December 31, 2007; 179(7): 1523 - 1537. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. M. Wishart, J. M. Paterson, D. M. Short, S. Meredith, K. A. Robertson, C. Sutherland, M. A. Cousin, M. B. Dutia, and T. H. Gillingwater Differential Proteomics Analysis of Synaptic Proteins Identifies Potential Cellular Targets and Protein Mediators of Synaptic Neuroprotection Conferred by the Slow Wallerian Degeneration (Wlds) Gene Mol. Cell. Proteomics, August 1, 2007; 6(8): 1318 - 1330. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. J. McCarran and M. P. Goldberg White Matter Axon Vulnerability to AMPA/Kainate Receptor-Mediated Ischemic Injury Is Developmentally Regulated J. Neurosci., April 11, 2007; 27(15): 4220 - 4229. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. H. Gillingwater, C. A. Ingham, K. E. Parry, A. K. Wright, J. E. Haley, T. M. Wishart, G. W. Arbuthnott, and R. R. Ribchester Delayed synaptic degeneration in the CNS of Wlds mice after cortical lesion Brain, June 1, 2006; 129(6): 1546 - 1556. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. H. Gillingwater, T. M. Wishart, P. E. Chen, J. E. Haley, K. Robertson, S. H.-F. MacDonald, S. Middleton, K. Wawrowski, M. J. Shipston, S. Melmed, et al. The neuroprotective WldS gene regulates expression of PTTG1 and erythroid differentiation regulator 1-like gene in mice and human cells Hum. Mol. Genet., February 15, 2006; 15(4): 625 - 635. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Bicho and C. Grewer Rapid Substrate-Induced Charge Movements of the GABA Transporter GAT1 Biophys. J., July 1, 2005; 89(1): 211 - 231. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Mi, B. Beirowski, T. H. Gillingwater, R. Adalbert, D. Wagner, D. Grumme, H. Osaka, L. Conforti, S. Arnhold, K. Addicks, et al. The slow Wallerian degeneration gene, WldS, inhibits axonal spheroid pathology in gracile axonal dystrophy mice Brain, February 1, 2005; 128(2): 405 - 416. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Samsam, W. Mi, C. Wessig, J. Zielasek, K. V. Toyka, M. P. Coleman, and R. Martini The Wlds Mutation Delays Robust Loss of Motor and Sensory Axons in a Genetic Model for Myelin-Related Axonopathy J. Neurosci., April 1, 2003; 23(7): 2833 - 2839. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
