Researchers at LMU Munich and Helmholtz Zentrum München have taken a significant step toward the understanding of how mature oligodendrocytes are generated in the adult brain. This is of great importance as loss of these cells leads to several debilitating diseases, including multiple sclerosis. The results of this study are now reported in ‘Nature Neuroscience’.
Oligodendrocytes are a part of the central nervous system that forms the so-called myelin sheath, an electrically insulating coat that is wrapped around the signal-transmitting processes (“axons”) of both sensory and motor neurons. This insulation increases the speed of impulse propagation along the axon, and is required for normal motor coordination, for instance. This function is exemplified by the effects of multiple sclerosis, one of several autoimmune diseases in which aberrant immune reactions lead to the localized destruction of myelin. Oligodendrocyte progenitor cells (OPCs) exist within the whole brain and as was recently discovered, they can generate mature, myelinating oligodendrocytes throughout life in a region dependent manner. In order to identify the reason for this difference in differentiation potential, Dr. Dimou, who is working at the Institute of Physiology at LMU Munich and at the Institute of Stem Cell Research (ISF), Helmholtz Zentrum München, and her colleagues have taken a closer look at the properties of OPCs from different brain regions.
The region-specific difference between OPCs lies in the fact that those located in the white matter – which consists primarily of nerve fibers – have a greater potential to generate myelinating oligodendrocytes than those in the gray matter, where the neuronal cell bodies are found. “Our aim was to discover whether this difference is cell-intrinsic or is dependent on the environment in which these cells are located,” says Dimou. To answer this question, her team carried out transplantation experiments in a mouse model system. Genetically marked donor OPCs from both white and gray matter were transplanted into both regions and their differentiation in the recipient mice was monitored over a period of several weeks. Dimou summarizes the findings as follows: “The results indicate that the differences are primarily intrinsic to the cells. While OPCs derived from the white matter give rise to myelin-producing oligodendrocytes with high efficiency irrespective of whether they are transplanted into white or gray matter, progenitors obtained from the gray matter are generating mature oligodendrocytes less effective.”
The next step is to identify the molecular factors responsible for this difference. “Our goal is to define conditions in which these progenitors will always differentiate into oligodendrocytes that form myelin,” Dimou explains. “We are still a long way from a practical therapy, but our studies represent an important advance in the quest to understand the origin and progression of demyelinating diseases such as multiple sclerosis.”
Viganò, F. et al. (2013). Transplantation reveals regional differences in oligodendrocyte differentiation in the adult brain, Nature Neuroscience, doi:10.1038/nn.3503
The Helmholtz Zentrum München, the German Research Center for Environmental Health, pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München is headquartered in Neuherberg in the north of Munich and has about 2,100 staff members. It is a member of the Helmholtz Association, a community of 18 scientific-technical and medical-biological research centers with a total of about 34,000 staff members. www.helmholtz-muenchen.de
The Institute of Stem Cell Research (ISF) investigates the basic molecular and cellular mechanisms of stem cell maintenance and differentiation. From that, the ISF then develops approaches in order to replace defect cell types, either by activating resting stem cells or by re-programming other existing cell types to repair themselves. The aim of these approaches is to stimulate the regrowth of damaged, pathologically changed or destroyed tissue.
Dr. Leda Dimou, Helmholtz Zentrum München – German Research Center for Environmental Health (GmbH), Institute of Stem Cell Research, Ingolstädter Landstr. 1, 85764 Neuherberg – Tel. +49-89-3187-3752 – E-Mail
Prof. Magdalena Götz, Helmholtz Zentrum München – German Research Center for Environmental Health (GmbH), Institute of Stem Cell Research, Ingolstädter Landstr. 1, 85764 Neuherberg – Tel. +49 89-3187-3750 – E-Mail