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Chromatin Structure in Scrapie and Alzheimer's Disease

Published online by Cambridge University Press:  18 September 2015

D.R. Crapper McLachlan*
Affiliation:
Departments of Physiology and Medicine, University of Toronto, Toronto
W.J. Lukiw
Affiliation:
Departments of Physiology and Medicine, University of Toronto, Toronto
H.J. Cho
Affiliation:
Animal Disease Research Institute, Agriculture Canada, Lethbridge, Alberta
R.I. Carp
Affiliation:
New York State Institute for Basic Research in Mental Retardation, Staten Island, New York
H. Wisniewski
Affiliation:
New York State Institute for Basic Research in Mental Retardation, Staten Island, New York
*
Dept. of Physiology, Medical Sciences Building, University of Toronto, Toronto, Ontario, Canada M5S 1A8
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Abstract:

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Scrapie affected brains exhibit a number of pathological features in common with the human neurodegenerative condition, Alzheimer's disease. The present report describes studies on chromatin structure seen in these two disease processes.

Chromatin associated proteins influence transcriptional activity of DNA through an effect upon chromatin structure. We examined chromatin structure by: (1) measuring the capacity of the enzyme micrococcal nuclease to release mono- and dinucleosomes from isolated nuclei and (2) measuring DN A-histone interactions by examining the effect of ambient tonicity upon the release of chromatin proteins.

In two strains of mice infected with two strains of scrapie agent there was reduced accessibility to micrococcal nuclease and an increased content on dinucleosomes of the histone HI and Hl° types. These changes precede clinical signs of scrapie and resemble those found in the human conditions of Alzheimer's and Pick's disease. Scrapie mouse brain differs from Alzheimer brain in that scrapie does not alter histone-DNA interactions as monitored by ionically induced histone release from chromatin. Despite similarities, the scrapie agent appears to operate upon different molecular mechanisms than those found in Alzheimer's disease.

Type
Cellular Clues to Pathogenesis
Copyright
Copyright © Canadian Neurological Sciences Federation 1986

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