Skip to main content Accessibility help
×
Home

Chromatin Structure in Scrapie and Alzheimer's Disease

  • D.R. Crapper McLachlan (a1), W.J. Lukiw (a1), H.J. Cho (a2), R.I. Carp (a3) and H. Wisniewski (a3)...

Abstract:

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.

    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Chromatin Structure in Scrapie and Alzheimer's Disease
      Available formats
      ×

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Chromatin Structure in Scrapie and Alzheimer's Disease
      Available formats
      ×

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Chromatin Structure in Scrapie and Alzheimer's Disease
      Available formats
      ×

Copyright

Corresponding author

Dept. of Physiology, Medical Sciences Building, University of Toronto, Toronto, Ontario, Canada M5S 1A8

References

Hide All
1.Bruce, M, Fraser, H.Amyloid plaques in the brains of mice infected with Scrapie: morphological variation and staining properties. Neuropathology and Applied Neurobiology 1975; 1: 189202.
2.Wisniewski, HM, Bruce, M, Fraser, H.Infectious etiology of neuritic (senile) plaques in mice. Science 1975: 190: 11081110.
3.Dickinson, AG, Bruce, ME, Scott, JR. In: Katzman, R (ed), Banbury Report 15, Biological aspects of Alzheimer’s Disease. New York, Cold Spring Harbor Laboratory Press 1983; 387398.
4.Wietgrefe, S, Zupancic, M, Hasse, A, Chesebro, B, Race, R, Frey, IIW, Rustan, T, Friedman, RL.Cloning of a gene whose expression is increased in scrapie and in senile plaques in human brain. Science 1985; 230: 11771179.
5.Bruce, M.Scrapie and Alzheimer’s Disease. Physiological Medicine 1984; 14: 497500.
6.Somerville, RA.Ultrastructural links between scrapie and Alzheimer’s Disease. Lancet March 1985; 504506.
7.Glenner, CW, Wong, CW.Alzheimer’s Disease: Initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochemical Biophysical Res Comm 1984; 120: 885890.
8.Masters, CL, Simms, G, Weinman, NA, Multhaup, G, McDonald, BL, Beyreuther, K.Amyloid plaque core protein in Alzheimer Disease and Down’s Syndrome. Proc Natl Acad Sci 1985; 82: 42454249.
9.Prusiner, SB.Prions: Novel infectious pathogens in advances in virus research. Academic Press 1984; 29: 156.
10.Chesebro, B, Race, R, Wehrly, K, Nishio, J, Bloom, M, Lechner, D, Bergstrom, S, Robbins, K, Mayer, L, Keith, JM, Garon, C, Hasse, A.Identification of scrapie prion protein specific mRNA in scrapie infected and uninfected brain. Nature 1985, 315: 331333.
11.Crapper, DR, Quittkat, S, De Boni, U.Altered chromatin conformation in Alzheimer’s Disease. Brain 1979; 102: 483495.
12.Lewis, PN, Lukiw, WJ, De Boni, U, Crapper McLachlan, DR.Changes in chromatin structure associated with Alzheimer’s Disease. J Neurochem November 1981; 37: 11931202.
13.Crapper McLachlan, DR, Lewis, PN, Lukiw, WJ, Sima, A, Bergeron, C, de Boni, U.Chromatin structure in dementia. Ann Neurol 1984; 15: 329334.
14.Chatigny, MA, Prusiner, SB.Biohazards and risk assessment of laboratory studies on the agents causing the spongiform encephalopathies in slow transmissible diseases of the nervous system. Academic Press 1979; 2: 491514.
15.Burton, K.Determination of DNA concentration with diphenylamine. Methods Enzymol 1968; 12B: 163166.
16.Cesarone, CF, Bolognesi, C, Santi, L.Improved microfluorometric DNA determination in biological material using 33258 Hoechst. Anal Biochem 1979; 100: 188197.
17.Biorad Technical Bulletin Biorad Protein Assay No. 1069; February 1979.
18.Heins, JN, Suriano, RJ, Taniuchi, H, Anfinsen, CB.Characterization of a nuclease produced by staphylococcus aureus. J Biol Chem 1967; 242 No. 5.
19.Thoma, F, Roller, T, Klug, A.Involvement of histone HI in the organization of the nucleosome and of the salt dependent superstructure of chromatin. J Cell Biol 1979; 83: 403427.
20.Manning, EJ, Lax, AJ, Kimberlin, RH.Polyadenylated RNA and scrapie in mice. Veterinary Microbiology 1982; 7: 267271.
21.Bountiff, L, Hunter, GD.Observations on a change in the low molecular weight cytoplasmic RNA in the brains of scrapie affected mice transactions. Biochemical Society 1982; 10:454458.
22.German, TL, McMillan, BC, Castle, BE, Dees, C, Wade, WF, Marsh, RF.Comparison of RNA from healthy and scrapie affected hamster brain. J Gen Virology 1985; 66: 839844.
23.Lerner, MR, Steitz, JA.Snurps and Scyrps. Cell 1981;25:298300.
24.Lukiw, WJ, Lewis, PN, McLachlan, DR.Analysis of chromatin from senile dementia affected brains. 12th International Congress of Biochemistry, Perth, Western Australia, August 1982; Poster Abstract 003–98.
25.Lukiw, WJ, Kruck, TPA and Crapper McLachlan, DR.Alterations in human linker histone — DNA binding in the presence of aluminum salts in vitro and in Alzheimer’s Disease. Submitted to Neuro Toxicology 1986.
26.Sadjel-Sulkowska, EM, Coughlin, JF, Staton, DM, Marotta, CA.In vitro protein synthesis by messenger RNA from the Alzheimer’s Disease brain from biological aspects of Alzheimer’s Disease. C.S.H.S.Q.B. Banbury Report No. 15, Katzman, R Editor, New York, 1982.
27.Guillemette, JG, Wong, L, Crapper McLachlan, DR, Lewis, PN.Characterization of messenger RNA from the cerebral cortex of control and Alzheimer affected brain. J Neurochem 1986; 47: 987997.

Metrics

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed