image: Dr. Gilad Levy (seated) & Prof. Boaz Barak.
Credit: Tel Aviv University
Researchers from Tel Aviv University have discovered a new biological mechanism that boosts the production of myelin - the fatty substance that insulates nerve fibers (axons) and enables rapid, efficient transmission of electrical signals between neurons in the brain and the body. The researchers: “Our findings may serve as the basis for developing innovative treatments for severe neurological disorders involving myelin damage, including multiple sclerosis, Alzheimer’s disease, and certain neurodevelopmental syndromes.”
The study was conducted in the laboratory of Prof. Boaz Barak of the Sagol School of Neuroscience and the School of Psychological Sciences at Tel Aviv University and was led by Dr. Gilad Levy. The lab collaborated with the laboratories of Dr. Asaf Marco from the Hebrew University of Jerusalem, Prof. Inna Slutsky and Prof. Yaniv Assaf from Tel Aviv University, Prof. Elior Peles from the Weizmann Institute of Science, and Prof. Hauke Werner from Germany. The findings were published in the prestigious journal Nature Communications.
Prof. Barak explains: “Damage to myelin is associated with a variety of neurodegenerative diseases such as Alzheimer’s disease and multiple sclerosis (an autoimmune disease in which the body itself attacks the myelin), as well as neurodevelopmental syndromes like Williams syndrome and autism spectrum disorders. In this study we focused on the cells that produce myelin in both the central and peripheral nervous systems. Specifically in these cells, we investigated the role of a protein called Tfii-i, known for its ability to increase or decrease the expression of many genes crucial for cell function. While Tfii-i has long been linked to abnormal brain development and neurodevelopmental syndromes, its role in myelin production had not been studied until now.”
Prof. Barak's team discovered that the Tfii-i acts as a 'biological brake' that inhibits myelin production in the relevant cells. Based on this finding, the researchers hypothesized that reducing Tfii-i activity in myelinating cells might increase myelin output. To test this, they used advanced genetic engineering in model mice: Tfii-i expression was selectively eliminated only in myelin-producing cells, while remaining unchanged in all other cells. These genetically modified mice were compared to normal mice in a wide variety of measures, including levels of myelin proteins, structure and thickness of the myelin sheath surrounding axons, speed of nerve signal conduction, and even motor and behavioral performance.
Dr. Gilad Levy explains: “We found that in the absence of Tfii-i, the myelin-producing cells generated higher amounts of myelin proteins. This resulted in abnormally thick myelin sheaths, which enhanced the conduction speed of electrical signals along the neural axons. These improvements resulted in a significant enhancement of the mice’s motor abilities, including better coordination and mobility, along with other behavioral benefits.”
Prof. Barak concludes: “In this study we demonstrated for the first time that it is possible to ‘release the brakes’ on myelin production in the brain and peripheral nervous system by regulating the expression of Tfii-i. This study is among the few to identify a mechanism for increasing myelin levels in the brain. Its results may enable the development of future therapies that suppress Tfii-i activity in myelin-producing cells, to restore myelin in a wide variety of degenerative and developmental diseases in which myelin is impaired — including Alzheimer’s disease, multiple sclerosis, Williams syndrome, and autism spectrum disorders. We believe this fundamentally new approach holds great therapeutic potential.”
Journal
Nature Communications