Animal Models Offer New Insights Into Energy Metabolism in Multiple Sclerosis

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Researchers at United Arab Emirates University in Abu Dhabi have recently published in the journal BMC Neuroscience new insights into the involvement of mitochondria and energy metabolism in the pathology of multiple sclerosis (MS) in rats. The study is entitled “Bioenergetics of the spinal cord in experimental autoimmune encephalitis of rats.

MS is a progressive neurodegenerative autoimmune disorder that results from an attack to the central nervous system by the body’s own immune system (auto-reactive T cells), causing inflammation and damage to the myelin layer that covers and protects nerve fibers. Myelin loss leads to impairment in signal transmission along the nerve fibers, affecting motor function (coordination, balance, speech and vision), and causing irreversible neurological disability and paralysis. It is estimated that more than 2.3 million people in the world suffer from multiple sclerosis.

Mitochondria are small cellular organelles responsible for the production of energy (in the form of ATP) in the body through the process of respiration. Mitochondrial dysregulation has been linked to axonal damage and demyelination in MS human patients and the corresponding experimental autoimmune encephalomyelitis (EAE) model in mice. Curiously, rodents have been reported to apparently recover from EAE with minimal neurological deficits. This recovery is thought to be linked to a downregulation of pro-inflammatory factors and clearance of infiltrating immune cells (T cells).

The cellular bioenergetics (energy metabolism) of the central nervous system (CNS) during the early development and clinical course of EAE has, however, been poorly investigated. In this study, the team hypothesized that the CNS bioenergetics may be used as a prognosis predictor of the disease and that it may explain disease remission in rodents, a recovery time where animals experience few or no symptoms. EAE susceptible and resistant rats were used and their oxygen consumption and ATP concentration in the spinal cord tissue were determined. Cell death (or apoptosis) was also assessed.

Researchers observed that in terms of cellular respiration in the CNS, no difference was found between diseased and healthy rats. Significant inflammation and apoptosis events were, however, observed in EAE susceptible animals, suggesting that both processes play a relevant role in the development of clinical disease, having little effect on mitochondrial function. These animals exhibited smaller mitochondria in the spinal cord regions with immune infiltrates. Demyelination events were also found in these specific regions at the initial stage of the disease.

The research team concluded that EAE at an early stage does not seem to significantly affect the CNS cellular respiration and ATP content, suggesting that the role played by mitochondria in demyelination and EAE development is minimal. The team hypothesizes that the recovery of rats with EAE might be due to the presence of a large population of functional mitochondria in regions of the spinal cord that have not been affected by the disease (no immune infiltrates). Based on the findings, the research team suggests that any intervention based on preserving the energy metabolism in EAE animals will likely improve disease outcome. Further studies are required to determine how these findings can be translated into the human context.

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Patrícia holds her PhD in Medical Microbiology and Infectious Diseases from the Leiden University Medical Center in Leiden, The Netherlands. She has studied Applied Biology at Universidade do Minho and was a postdoctoral research fellow at Instituto de Medicina Molecular in Lisbon, Portugal. Her work has been focused on molecular genetic traits of infectious agents such as viruses and parasites.
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One comment

  1. Greg says:

    Hi, a great article and study.

    It may be worthwhile your readers looking into MitoQ. This is a specific mitochondria-targeted antioxidant and we are getting some great results. Thanks. Greg

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