Document Detail


The Wld(S) mutation delays anterograde, but not retrograde, axonal degeneration of the dopaminergic nigro-striatal pathway in vivo.
MedLine Citation:
PMID:  20132467     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
For many neurodegenerative disorders, such as Parkinson's disease, there is evidence that the disease first affects axons and terminals of neurons that are selectively vulnerable. This would suggest that it may be possible to forestall progression by targeting the cellular mechanisms of axon degeneration. While it is now clear that these mechanisms are distinct from the pathways of programmed cell death, they are less well known. Compelling evidence of the distinctiveness of these mechanisms has derived from studies of the Wld(S) mutation, which confers resistance to axon degeneration. Little is known about how this mutation affects degeneration in dopaminergic axons, those that are affected in Parkinson's disease. We have characterized the Wld(S) phenotype in these axons in four models of injury: two that utilize the neurotoxin 6-hydroxydopamine or axotomy to induce anterograde degeneration, and two that use these methods to induce retrograde degeneration. For both 6-hydroxydopamine and axotomy, Wld(S) provides protection from anterograde, but not retrograde degeneration. This protection is observed as preserved immunostaining for tyrosine hydroxylase in axons and striatum, and by structural integrity visualized by GFP in tyrosine hydroxylase-GFP mice. Therefore, Wld(S) offers axon protection, but it reveals fundamentally different processes underlying antero- and retrograde degeneration in this system.
Authors:
Hsiao-Chun Cheng; Robert E Burke
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-02-01
Journal Detail:
Title:  Journal of neurochemistry     Volume:  113     ISSN:  1471-4159     ISO Abbreviation:  J. Neurochem.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-04-16     Completed Date:  2010-05-04     Revised Date:  2014-09-20    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  England    
Other Details:
Languages:  eng     Pagination:  683-91     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / physiology
Axons / pathology*
Axotomy
Dopamine / physiology*
Female
Green Fluorescent Proteins
Hydroxydopamines / toxicity
Immunohistochemistry
Medial Forebrain Bundle / metabolism,  pathology
Mice
Mice, Inbred C57BL
Microscopy, Confocal
Mutation / physiology*
Neostriatum / physiology*
Nerve Degeneration / genetics*,  pathology
Nerve Tissue Proteins / genetics*
Neural Pathways / physiology*
Promoter Regions, Genetic / genetics
Substantia Nigra / physiology*
Tyrosine 3-Monooxygenase / metabolism
Grant Support
ID/Acronym/Agency:
NS26836/NS/NINDS NIH HHS; NS38370/NS/NINDS NIH HHS; P50 NS038370/NS/NINDS NIH HHS; P50 NS038370-11/NS/NINDS NIH HHS; P50 NS038370-115284/NS/NINDS NIH HHS; R01 NS026836/NS/NINDS NIH HHS; R01 NS026836-19/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Hydroxydopamines; 0/Nerve Tissue Proteins; 0/Wld protein, mouse; 147336-22-9/Green Fluorescent Proteins; EC 1.14.16.2/Tyrosine 3-Monooxygenase; VTD58H1Z2X/Dopamine
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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