A question of heritage
Researchers at LMU 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.
Oligodendrocytes are an 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. “It is rather like damaging the insulating mantle around an electrical cable,” explains Dr. Leda Dimou, who is working at the Institute of Physiology at LMU Munich.
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 and her colleagues have taken a closer look at the properties of OPCs from different brain regions. The results of this study are now reported in Nature Neuroscience.
Intrinsic vs. extrinsic factors
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.” (Nature Neuroscience 2013) nh