Multiple sclerosis, also known as encephalomyelitis disseminata is a neurodegenerative disease characterized by damage to the white matter in the brain and spinal cord (central nervous system. The mitochondria are implicated in MS disease progression. With that said, lifestyle changes that improve mitochondrial health might be a way to delay/slow disease progression and disability. In this article, you will learn about the structure and function of the central nervous system (brain and spinal cord), mitochondrial structure and function, and how mitochondrial dysfunction may play a role in disease progression.
Structure and function brain and spinal cord
The brain is made up of two types of nerve cells. Neurons and microglia.
Neurons are the cells that are responsible for getting the body to function properly (more on that in the next section).
Microglia are the “support cells”. Microglia are made up of astrocytes, oligodendrocytes and glial cells. Astrocytes are the cells that bring provisions from the blood vessels to the neurons. Oligodendrocytes are the cells that produce the myelin sheath that wraps around the axon to allow an electrical impulse to conduct from one cell body to another. And finally, the glial cells are immune cells that keep the brain clean.
Neuron structure and function
Neurons are made up of a cell body, an axon, and dendrites. The cell body is a fluid filled sac filled with DNA, lipids, fats, proteins, signaling molecules, and mitochondria that keep a cell functioning.
The axon is a long tail that extends from the cell body to connect one cell body to another. At the end of each axon is an axon terminal that consists of small vesicles that store and release neurotransmitters (chemicals that will communicate a message from one neuron to the next). Dendrites extend from the cell body and receive chemical messages (neurotransmitters) from the axon terminals of an adjacent neuron.
Structure and function of mitochondria
Mitochondria are structures in the neuron called organelles. These oval shaped structures are encased with a double membrane. Mitochondria make their own DNA, called mtDNA. Interesting fact, offspring inherit mtDNA from their mothers and therefor mtDNA is a great way to study maternal lineage.
The main job of mitochondria is to use oxygen to turn glucose into energy, called ATP. This process is called oxidative phosphorylation (OXPHOS) and will become important as we get into the mechanisms behind multiple sclerosis.
In addition to producing energy, mitochondria also control the calcium in the cell, are involved in cell signaling and are involved in cell death (by overloading the cell with calcium)
Free Radicals, antioxidants and oxidative stress
When talking about mitochondria, it is important to mention free radicals. Free radicals are unstable molecules with one unpaired electron (electrons like to stay in pairs). To become a “stable molecule”, free radicals either need to steal or give away an electron. Thus making another molecule unstable. In excess, free radicals cause cell damage.
Reactive oxygen species (ROS) are free radicals released in the mitochondria during the process of oxidative phosphorylation (OXPHOS)- discussed above. ROS can also be released from immune cells, fat cells, and damaged cells. In some instances, ROS and other free radicals are necessary and in fact beneficial. For example, when released from immune cells during a normal immune response, they can destroy potentially harmful molecules. However, too many can cause mitochondria to cell damage. To prevent free radicals from accumulating, they are neutralized by the antioxidant defense system. An imbalance between the number of free radicals and the ability of the antioxidant defense system leads to oxidative stress.
Neuroinflammation and Glia In Multiple Sclerosis
Neuroinflammation is inflammation of the central nervous system and is the primary driver of multiple sclerosis. This inflammatory process in the brain is initiated when perpheral immune cells pass the blood brain barrier, and enter the brain. These peripheral immune cells release inflammatory cytokines that activate the glial cells (the brain’s immune cells). Some of these immune cells release reactive oxygen species (ROS), tumor necrosis factor (TNF), reactive nitrogen species (RNS), and glutamate.
This rise in ROS causes mitochondria to malfunction. Malfunctioning mitochondria produce less energy and more ROS. Less energy production means impaired neurotransmitter transmission and other critical nerve cell functions. Decreased nerve transmission is one explanation for brain fog, fatigue, and depression associated with MS.
Mitochondrial Dysfunction and the Future of Multiple Sclerosis Treatment
“Mitochondrial metabolism has a role in the inflammation cascade and targeting the metabolism of innate immune cells may be of benefit.”
Novel therapies could have the potential to reduce chronic neuroinflammation as a way of preventing secondary neurologic damage including:
- Therapies that support cellular metabolism such as high dose biotin, iron and vitamin D [studies looking at each of these treatments are ongoing (https://clinicaltrials.gov)]
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Gene therapies are being developed in mitochondrial disorders, though most are still in the early phases of development