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Lookup NU author(s): Dr Don Mahad, Mark Cadogan
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Synaptic and dendritic pathology is a well-documented component of prion disease. In common with other neurodegenerative diseases that contain an element of protein misfolding, little is known about the underlying mechanisms of synaptic degeneration. In particular, in prion disease the relationship between synaptic malfunction, degeneration, and mitochondria has been neglected. We investigated a wide range of mitochondrial parameters, including changes in mitochondrial density, inner membrane ultrastructure, functional properties and nature of mitochondrial DNA from hippocampal tissue of mice with prion disease, which have ongoing synaptic pathology. Our results indicate that despite a lack of detectable changes in either mitochondrial density or expression of the mitochondrial proteins, mitochondrial function was impaired when compared with age-matched control animals. We observed changes in mitochondrial inner membrane morphology and a reduction in the cytochrome c oxidase activity relative to a sustained level of a mitochondrial proteins such as porin and individual, functionally important subunits of complex II and complex IV. These data support the idea that mitochondrial dysfunction appears to occur due to inhibition or modification of respiratory complex rather than deletions of mitochondrial DNA. Indeed, these changes were seen in the stratum rediatum where synaptic pathology is readily detected, indicating that mitochondrial function is impaired and could potentially contribute to or even initiate the synaptic pathology in prion disease. (Am J Pathol 2010, 177:1411-1421; DOI: 10.2353/ajpath.2010.091037)
Author(s): Siskova Z, Mahad DJ, Pudney C, Campbell G, Cadogan M, Asuni A, O'Connor V, Perry VH
Publication type: Article
Publication status: Published
Journal: American Journal of Pathology
Year: 2010
Volume: 177
Issue: 3
Pages: 1411-1421
Print publication date: 22/07/2010
ISSN (print): 0002-9440
ISSN (electronic): 1525-2191
Publisher: American Society for Investigative Pathology
URL: http://dx.doi.org/10.2353/ajpath.2010.091037
DOI: 10.2353/ajpath.2010.091037
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