Document Detail

Cytoskeletal changes in rat cortical neurons induced by long-term intraventricular infusion of leupeptin.
MedLine Citation:
PMID:  7709735     Owner:  NLM     Status:  MEDLINE    
Neurofibrillary tangles (NFTs), which are composed of paired helical filament (PHF)-like filaments, were induced by the long-term intraventricular infusion of leupeptin, a potent protease inhibitor. The fibrils composing the NFTs were 20 nm in maximal width and had periodic constrictions at 40-nm intervals. They were identical to the PHF that had been found in aged rat neurons. Dystrophic axons filled with mainly tubular structures were also abundantly found in the parietal and temporal isocortices, which were not affected in the acute or subacute phases of leupeptin treatment. An immunohistochemical study using antibodies related to the neuronal cytoskeleton showed that neuronal cytoskeletal changes accompanying ubiquitination occurred in dystrophic axons distributed widely in the isocortex as well as the hippocampal formation. The present findings suggest that long-term administration of leupeptin accelerates the neuronal ageing process in rats and causes other neuronal changes: NFT formation, such as seen in the aged brain or in neurodegenerative diseases including Alzheimer's disease, in addition to accumulation of lipofuscin granules and degeneration of neuronal processes. In other words, some disturbance of the balance between proteases and their inhibitors may play an important role in the neuronal ageing process, and some regulatory intervention in the intraneuronal protease activity may provide a new therapeutic strategy for the neurodegenerative diseases.
S Takauchi; K Miyoshi
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Acta neuropathologica     Volume:  89     ISSN:  0001-6322     ISO Abbreviation:  Acta Neuropathol.     Publication Date:  1995  
Date Detail:
Created Date:  1995-05-10     Completed Date:  1995-05-10     Revised Date:  2007-11-09    
Medline Journal Info:
Nlm Unique ID:  0412041     Medline TA:  Acta Neuropathol     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  8-16     Citation Subset:  IM    
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MeSH Terms
Alzheimer Disease / pathology
Cerebral Cortex / pathology*
Disease Models, Animal
Injections, Intraventricular
Leupeptins* / administration & dosage
Models, Neurological
Nerve Degeneration
Neurofibrillary Tangles / ultrastructure*
Parietal Lobe / ultrastructure
Rats, Wistar
Reg. No./Substance:
0/Leupeptins; 24365-47-7/leupeptin
Erratum In:
Acta Neuropathol (Berl) 1996 Dec;92(6):645

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

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