Related Experiment Video
Updated: Aug 9, 2026
Methods for In situ Quantification of Mitochondrial Morphology in Muscle and Terminal Schwann Cells of Mice
Published on: April 10, 2026
Increased axonal mitochondrial activity as an adaptation to myelin deficiency in the Shiverer mouse
Helen Andrews1, Kathryn White, Christine Thomson
1Department of Neurology, The Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom.
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.
Insights
In the absence of myelin, axons increase mitochondria for energy, potentially leading to damage from reactive oxygen species (ROS). This study found adaptive mitochondrial increases in dysmyelinated axons, offering insights into chronic demyelination.
Area of Science:
- Neuroscience
- Cell Biology
- Pathology
Background:
- Axonal pathology is a key feature of multiple sclerosis (MS), contributing to disability.
- Mitochondrial dysfunction and oxidative damage are implicated in chronic MS lesions.
- The energy demands of demyelinated axons may lead to mitochondrial adaptations.
Purpose of the Study:
- To investigate if chronic myelin absence induces adaptive mitochondrial changes in axons.
- To understand how axons cope with sustained demyelination in a non-inflammatory context.
Main Methods:
- Utilized the shiverer mouse model, a mutant lacking myelin basic protein.
- Employed cytochrome c histochemistry to assess mitochondrial activity.
- Used electron microscopy to quantify mitochondrial numbers within axons.
Main Results:
- Shiverer mice exhibited a twofold increase in mitochondrial activity in white matter tracts.
- Electron microscopy confirmed a significantly higher number of mitochondria in dysmyelinated axons.
- Demonstrated adaptive mitochondrial proliferation within CNS axons lacking myelin.
Conclusions:
- Axons undergo adaptive changes involving mitochondria in response to chronic myelin loss.
- These findings provide insights into axonal responses in chronically demyelinated conditions, relevant to MS.
- Mitochondrial adaptation may represent a compensatory mechanism in the face of sustained energy demands in demyelinated axons.
