The series of images display cross-sectional electron micrographs of individual nerve fibres in brain biopsies of individuals with multiple sclerosis. The images show axons with myelin sheaths (depicted as black rings), illustrating increasingly severe damage from images 1 to 8. The spectrum of damage ranges from the accumulation of individual cellular components in otherwise bright, intact axons (image 1) to advanced degeneration in irreversibly damaged, dark axons (image 8). Photo credit: Leipzig University
Multiple sclerosis (MS) is a serious neurological disease that often leads to permanent disability. It affects approximately 2.9 million people worldwide, with 240,000 cases in Germany alone. The exact cause of the disease is not yet clear, but a key characteristic is the loss of the protective myelin coating on nerve connections in the central nervous system. This loss is caused by autoimmune processes. The myelin is created by specialized glial cells called oligodendrocytes and allows for fast transmission of nerve impulses. In MS, it is believed that immune cells break down oligodendrocytes and myelin, leading to irreversible damage to the vulnerable nerve connections. The loss of these nerve connections is a major factor in the severity and progression of MS.
Recent research suggests that our understanding of diseases needs to change. Myelin, previously thought to be only protective, can actually threaten the survival of axons when attacked by immune cells. Oligodendrocytes not only form myelin but also support the energy metabolism of axons. Myelinated axons rely on metabolic support and need intact myelin architecture for maintenance.
“When oligodendrocytes are exposed to an acute inflammatory environment, they may lose their ability to support the axons, and myelin becomes a threat to the survival of the axons,” says Professor Klaus-Armin Nave from the Max Planck Institute for Multidisciplinary Sciences in Göttingen, Germany. To test their hypothesis, the researchers examined tissue samples from patients with multiple sclerosis, as well as various mouse models of this disease in order to experimentally simulate the autoimmune attack on myelin. For the first time, the researchers were able to demonstrate by electron microscopy in the tissue samples of the patients that irreversible damage almost always occurs in the axons that are still coated with myelin. Conversely, using genetically modified mouse models, the researchers were able to show that “naked” axons in an acute inflammatory region of the central nervous system are better protected from degeneration.
Professor Ruth Stassart from the Paul Flechsig Institute suggests gaining a deeper understanding of myelin and developing new treatment strategies. Dr. Robert Fledrich adds that promoting rapid degradation of damaged myelin might be therapeutically better.