Document Detail


Neurofilament reorganisation and neurofilament antigen redistribution in spinal motoneurones following retrograde axonal transport of diphtheria toxin.
MedLine Citation:
PMID:  7511315     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Single unilateral injections of diphtheria toxin (DTX) into the external anal sphincter muscle or internal intercostal nerve of cat induced characteristic ultrastructural lesions in corresponding ipsilateral spinal motoneurones 6-8 days later. The chief neuronal lesion was a progressive disruption of Nissl body composition and organisation, which between days 8-19 post injection was accompanied by a progressive accumulation of neurofilaments in motoneuronal perikarya and dendrites. Some axons in the ipsilateral ventral horn became hypertrophied due to neurofilamentous accumulation. Related immunocytochemical investigations 6-35 days after injection of DTX revealed abnormal immunoreactivity intoxicated motoneurones for 200-kDa and 160-kDa phosphorylated neurofilament proteins, but not in contralateral motoneurones. By day 35 abnormal neurofilament immunostaining also occurred in ipsilateral and some contralateral interneurones but not contralateral motoneurones. Abnormalities of Nissl body endoplasmic reticulum, neurofilament organisation, and neurofilament protein immunostaining were identical after either intraneural and intramuscular injections of DTX, indicating abnormalities were attributable to toxicity and not injection-related axonal damage. Since DTX acts specifically in the soma to inhibit protein synthesis, neurofilament abnormalities are secondary to cytotoxicity and probably result from deficits in transference of existing partially phosphorylated neurofilaments to the axonal transport system, or axonal transport per se.
Authors:
A H Pullen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Acta neuropathologica     Volume:  87     ISSN:  0001-6322     ISO Abbreviation:  Acta Neuropathol.     Publication Date:  1994  
Date Detail:
Created Date:  1994-04-22     Completed Date:  1994-04-22     Revised Date:  2009-09-29    
Medline Journal Info:
Nlm Unique ID:  0412041     Medline TA:  Acta Neuropathol     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  32-46     Citation Subset:  IM    
Affiliation:
Sobell Department of Neurophysiology, Institute of Neurology, London, UK.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Monoclonal
Axonal Transport
Cats
Diphtheria Toxin / pharmacokinetics,  toxicity*
Functional Laterality
Microscopy, Electron
Motor Neurons / drug effects,  pathology*,  ultrastructure
Neurofibrils / drug effects,  pathology*,  ultrastructure
Neurofilament Proteins / analysis,  biosynthesis
Reference Values
Spinal Cord / drug effects,  pathology*,  ultrastructure
Grant Support
ID/Acronym/Agency:
//Wellcome Trust
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Diphtheria Toxin; 0/Neurofilament Proteins

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