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Increased axonal mitochondrial activity as an adaptation to myelin deficiency in the Shiverer mouse

Lookup NU author(s): Dr Helen Andrews, Dr Kathryn White, Emeritus Professor David Bates, Emeritus Professor Doug Turnbull, Dr Philip Nichols

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Abstract

Axonal pathology in multiple sclerosis (MS) has been described for over a century, but new insights into axonal loss and disability have refocused interest in this area. There is evidence of oxidative damage to mitochondrial DNA in chronic MS plaques, suggesting that mitochondrial failure may play a role in MS pathology. We propose that in the chronic absence of myelin the maintenance of conduction relies partially on an increase in mitochondria to provide energy. This increased energy requirement also promotes reactive oxygen species (ROS), because most intraaxonal ROS are generated by mitochondria. If antioxidant defenses are overwhelmed by an excess of ROS, this may result in damage to the axon. Our aim was to investigate whether a chronic lack of myelin results in adaptive changes involving mitochondria within the axon. We investigated this in the shiverer mouse. This myelin basic protein gene mutant provides a model of how adult central nervous system (CNS) axons cope with the chronic absence of a compact myelin sheath. Cytochrome c histochemistry demonstrated a twofold increase in mitochondrial activity in white matter tracts of shiverer, and electron microscopy confirmed a significantly higher number of mitochondria within the dysmyelinated axons. Our data demonstrate that there are adaptive changes involving mitochondria occurring within CNS axons in shiverer mice in response to a lack of myelin. This work contributes to our understanding of the adaptive changes occurring in response to a lack of myelin in a noninflammatory environment similar to the situation seen in chronically demyelinated MS plaques. © 2006 Wiley-Liss, Inc.

Publication metadata

Author(s): Andrews H, White K, Thomson C, Edgar J, Bates D, Griffiths I, Turnbull D, Nichols P

Publication type: Article

Publication status: Published

Journal: Journal of Neuroscience Research

Year: 2006

Volume: 83

Issue: 8

Pages: 1533-1539

ISSN (print): 0360-4012

ISSN (electronic): 1097-4547

Publisher: John Wiley & Sons, Inc.

URL: http://dx.doi.org/10.1002/jnr.20842

DOI: 10.1002/jnr.20842

PubMed id: 16555298

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