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Morphological and Functional Abnormalities in Mitochondria Associated with Synaptic Degeneration in Prion Disease

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)

Publication metadata

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


DOI: 10.2353/ajpath.2010.091037


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Funder referenceFunder name
G0501636UK Medical Research Council (MRC)