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Morphological and functional abnormalities in mitochondria associated with synaptic degeneration in prion disease

Record type: Article

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 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 radiatum 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.

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Citation

Sisková, Zuzana, Mahad, Don Joseph, Pudney, Carianne, Campbell, Graham, Cadogan, Mark, Asuni, Ayodeji, O'Connor, Vincent and Perry, Victor Hugh CNS Inflammation Group, University of Southampton (2010) Morphological and functional abnormalities in mitochondria associated with synaptic degeneration in prion disease The American Journal of Pathology, 177, (3), pp. 1411-1421. (doi:10.2353/ajpath.2010.091037). (PMID:20651247).

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Published date: September 2010

Identifiers

Local EPrints ID: 180203
URI: http://eprints.soton.ac.uk/id/eprint/180203
ISSN: 0002-9440
PURE UUID: fdab1a50-a2da-4627-984f-617daf6c03a7

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Date deposited: 06 Apr 2011 07:38
Last modified: 18 Jul 2017 12:01

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Contributors

Author: Zuzana Sisková
Author: Don Joseph Mahad
Author: Carianne Pudney
Author: Graham Campbell
Author: Mark Cadogan
Author: Ayodeji Asuni

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