Multiple sclerosis (EM) affects approximately 2.3 million people worldwide. Approximately 80% of people with EM have inflammation in the cerebellum, the part of the brain that helps control movement and balance, which can generate tremors, poor coordination and problems with motor control. These problems often persist and can get worse over time, since the cerebellum gradually loses healthy brain tissue.
A Riverside study of the University of California, published today in the minutes of the National Academy of Sciences, now sheds light on the underlying mechanisms of cerebellar degeneration in EM, which suggests that mitochondrial dysfunction can play a key role in the progressive loss of neuronal cells called purkinje cells and motor heights.
EM is marked by chronic inflammation and demyelination in the central nervous system. Demonicization is the process in which myelin sheath, a protective and insulating layer that surrounds nerve fibers in the brain and spinal cord, is damaged or lost. This interruption interferes with the normal transmission of electrical signals along the nerves, resulting in various neurological problems. Mitochondria are vital structures within the cells that generate most of the cell energy, which are worth the nickname of the “powers” of the cell.
“Our study, conducted by my graduated student Kelley Atkinson, proposes that inflammation and demyelination in the mitochondrial function of the cerebellum interrupt the mitochondrial function, contributing to the nervous damage and the loss of purkin cells,” said Sema Tiwari-Woodruff, a biomedical science professor at the Riverside School of Medicine of UC Riversid of the research team. “We observe a significant loss of COXIV mitochondrial protein in demyelinized Purkinje cells, suggesting that mitochondrial deterioration contributes directly to cell death and cerebellar damage.”
Purkinje cells
When we walk or move, many parts of our brain and body work together: our muscles, spine, eyes, ears and especially our brain. A key brain area for movement and balance is the cerebellum.
Inside the cerebellum there are special cells called purkinje neurons. These large and highly active cells help coordinate soft and precise movements, such as dancing, throwing a ball or even walking. They are essential for balance and fine motor skills. “
Sema Tiwari-Woodruff, Professor of Biomedical Sciences, UC Riverside School of Medicine
Tiwari-Woodruff explained that in diseases such as MS, the cerebellum can be damaged, and Purkinje cells often begin to die. This leads to problems with coordination and movement, a condition known as ataxia.
“Our research analyzed the brain tissue of patients with EM and found important problems in these neurons: they had less branches, they were losing myelin and had mitochondrial problems, which means that their energy supply was failing,” said Tiwari -Woodruff. “Because Purkinje cells play such a central role in movement, their loss can cause serious mobility problems. Understand why they are damaged in EM could help us find better treatments to protect movement and balance in people with the disease.”
Off
The team also used a well -established mouse model known as experimental autoimmune encephalomyelitis (EAE), a mouse model that develops symptoms similar to EM, to investigate mitochondrial disorders during the progression of the disease.
The researchers found that EAE mice lost Purkinje cells over time, just like people with EM.
“The remaining neurons do not work so well because their mitochondria, the energy producing parts, begin to fail,” said Tiwari-Woodruff. “We also saw that myelin breaks down early in the disease. These problems (less energy, myelin loss and damaged neurons) begin early, but the real death of brain cells tends to occur later, as the disease becomes more serious. The loss of energy in brain cells seems to be a key part of what causes damage to EM.”
Although the mouse model does not capture all aspects of EM, its similarities with human disease make it a valuable tool to study neurodegeneration and test possible therapies.
“Our findings offer critical ideas about the progression of cerebellar dysfunction in EM,” said Tiwari-Woodruff. “Directing mitochondrial health can represent a promising strategy to stop or prevent neurological deterioration and improve the quality of life of people living with EM. This research brings us one more step to understand the complex mechanisms of EM and develop more effective and specific treatments for this weakening disease.”
Feeding the future
Next, the team will investigate whether the mitochondrial deterioration found in Purkinje cells also affects other brain cells such as oligodendrocytes, which help form white matter, or astrocytes, which support the general brain function.
“To respond to this, one of our ongoing research projects focuses on studying mitochondria in specific types of brain cells in the cerebellum,” said Tiwari-Woodruff. “This research can open the door to find ways to protect the brain from the beginning, such as increasing energy in brain cells, helping them repair their protective myelin coating or calming the immune system before too much damage is done. This is especially important for people with MS who fight with balance and coordination, since these symptoms are engaged in damage to the cerebellum.”
Tiwari-Woodruff emphasized that disease-related research is vital to improve lives.
“Cutting funds for science only decreases progress when we need it most,” he said. “Public support for research is more important than ever.”
Tiwari-Woodruff and Atkinson joined in the studio of Shane DaS, Micah Feria, Maria T. Sekyia, Marvelous Osunde, Sandhya Sriram, Saima Meoria, Wendy Rincóna and Britany Belloa.
The research team analyzed the postmortem cerebellar fabric of patients with secondary progressive EM, along with samples of healthy individuals, obtained from the National Institutes of Health of Neurobiobank and the Cleveland Clinic.
The study was supported by a subsidy of the National Society of Multiple Sclerosis.
Research work is entitled “Decreased mitochondrial activity in the demyelinizing cerebellum of progressive multiple sclerosis and chronic EAE contributes to the loss of purkinje cells.”
Fountain:
University of California – Riverside
(Tagstotranslate) Brain
