Document Detail


Olivocerebellar projections modify hereditary Purkinje cell degeneration.
MedLine Citation:
PMID:  11074164     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Brainstem inferior olivary neurons, through their olivocerebellar efferent projections, dynamically regulate the structure and function of Purkinje neurons. To test the hypothesis that the inferior olive can epigenetically modify adult-onset hereditary Purkinje cell death, olivocerebellar projections were destroyed by 3-acetylpyridine chemoablation of the inferior olive in Shaker mutant rats. Starting around seven weeks of age, mutant Purkinje cells degenerate in a highly predictable spatial and temporal pattern. Chemoablation of the inferior olive at the onset of hereditary Purkinje cell degeneration accelerated the temporal pattern of Purkinje cell death from a natural phenotypic course of six to eight weeks to one and two weeks. When chemoablation of the inferior olive was performed three and a half weeks earlier, the onset of Purkinje cell death was accelerated by seven to 10days, but the spatial pattern and natural rate of temporal degeneration was maintained. Chemoablation of the inferior olive in normal rats did not result in any apparent death of Purkinje cells. These findings indicate that the olivocerebellar system can markedly modify hereditary Purkinje cell death. The accelerated death of Purkinje cells following chemoablation of the inferior olive can result from either the interruption of a trophic signal by climbing fiber deafferentation or parallel fiber excitotoxicity due to cortical disinhibition, but not due to olivocerebellar excitotoxicity.
Authors:
D L Tolbert; B R Clark
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Neuroscience     Volume:  101     ISSN:  0306-4522     ISO Abbreviation:  Neuroscience     Publication Date:  2000  
Date Detail:
Created Date:  2001-01-04     Completed Date:  2001-02-01     Revised Date:  2009-11-03    
Medline Journal Info:
Nlm Unique ID:  7605074     Medline TA:  Neuroscience     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  417-33     Citation Subset:  IM    
Affiliation:
Francis and Doris Murphy Neuroanatomy Research Laboratory, Department of Anatomy and Neurobiology, and Department of Surgery (Neurosurgery), Saint Louis University School of Medicine, St Louis, MO 63104, USA. tolbertd@slu.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Behavior, Animal / drug effects,  physiology
Calcium-Binding Protein, Vitamin D-Dependent / metabolism
Cell Survival / drug effects,  physiology
Cerebellar Cortex / drug effects,  pathology,  physiopathology*
Denervation / adverse effects
Disease Models, Animal
Harmaline / pharmacology
Male
Nerve Degeneration / chemically induced,  genetics,  pathology,  physiopathology*
Neural Pathways / drug effects,  pathology,  physiopathology*
Neurotoxins / pharmacology
Niacinamide / pharmacology
Olivary Nucleus / drug effects,  pathology,  physiopathology*
Parvalbumins / metabolism
Purkinje Cells / drug effects,  metabolism*,  pathology
Pyridines / pharmacology
Rats
Rats, Mutant Strains
Rats, Sprague-Dawley
Rats, Wistar
Spinocerebellar Degenerations / genetics,  pathology,  physiopathology*
Chemical
Reg. No./Substance:
0/Calcium-Binding Protein, Vitamin D-Dependent; 0/Neurotoxins; 0/Parvalbumins; 0/Pyridines; 0/calbindin; 304-21-2/Harmaline; 350-03-8/3-acetylpyridine; 98-92-0/Niacinamide

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


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