Mitochondrial Dysfunction Linked to Brain Damage in Multiple Sclerosis
A new study illuminates how damage to the cerebellum, a key brain region for movement and balance, occurs in multiple sclerosis. The research identifies a link between mitochondrial dysfunction and the degeneration of crucial nerve cells, offering potential targets for future treatments.
Unraveling Cerebellar Degeneration
The University of California, Riverside study, published in the Proceedings of the National Academy of Sciences, investigates the mechanisms behind cerebellar degeneration in multiple sclerosis. Researchers suggest that mitochondrial impairment significantly contributes to the loss of Purkinje cells, worsening motor issues.
The research team, led by Seema Tiwari-Wodrufff, observed that inflammation and demyelination in the cerebellum disrupt mitochondrial function. This disruption contributes to nerve damage and Purkinje cell loss. They found a significant loss of the mitochondrial protein COXIV in demyelinated Purkinje cells, suggesting mitochondrial impairment directly contributes to cell death and cerebellar damage.
“Our study proposes that inflammation and demyelination in the cerebellum disrupt mitochondrial function, contributing to nerve damage and Purkinje cell loss,”
—Seema Tiwari-Woodruff, Professor
Approximately 2.3 million individuals globally are impacted by multiple sclerosis, a condition marked by chronic inflammation and myelin sheath damage in the central nervous system. The myelin sheath protects nerve fibers in the brain and spinal cord, and its damage disrupts electrical signal transmission. The loss of Purkinje cells, vital for movement, leads to ataxia, causing mobility problems.
Delving into Purkinje Cells
The cerebellum is essential for movement and balance, particularly relying on Purkinje neurons to coordinate smooth, precise actions. According to Tiwari-Woodruff, these large cells are critical for fine motor skills.
In multiple sclerosis, the cerebellum can sustain damage, resulting in Purkinje cell death. This cell loss leads to coordination and movement problems. This study looked at brain tissue from MS patients and found major issues in these neurons: they had fewer branches, were losing myelin, and had mitochondrial problems — meaning their energy supply was failing. According to the National MS Society, MS affects roughly 1 in 770 people in the United States (National MS Society).
Mouse Model Insights
Researchers utilized a mouse model of MS, known as experimental autoimmune encephalomyelitis (EAE), to study mitochondrial alterations during disease progression. They found that the EAE mice lost Purkinje cells over time.
Tiwari-Woodruff noted that the remaining neurons do not function optimally because their mitochondria, which produce energy, begin to fail. Myelin breaks down early in the disease. These problems—reduced energy, myelin loss, and damaged neurons—start early, while brain cell death happens later as the disease worsens.
Future Directions
The team intends to explore whether mitochondrial impairment in Purkinje cells also affects other brain cells. Such research may find ways to protect the brain early on, like boosting energy in brain cells, assisting with the repair of their myelin coating, or calming the immune system. This is particularly important for people with multiple sclerosis, where balance and coordination issues are linked to cerebellum damage.
Tiwari-Wodruff emphasizes that this disease-related research is vital for improving lives. She stated that “Cutting funding to science only slows progress when we need it most. Public support for research matters now more than ever.”
