Image taken using an electron microscope of the cellular processes of nerve cells (gray) and their myelin sheaths (black ring-like structures) in a brain section. Image credit: Wiebke Möbius (CC BY 4.0)
Like the electrical wires in our homes, the processes of nerve cells – the axons, thin extensions that project from the cell bodies – need to be insulated to work effectively. This insulation takes the form of layers of a membrane called myelin, which is made of proteins and fats and produced by specialized cells called oligodendrocytes in the brain and the spinal cord. If this layer of insulation becomes damaged, the electrical impulses travelling along the nerves slow down, affecting the ability to walk, speak, see or think. This is the cause of several illnesses, including multiple sclerosis and a group of rare genetic diseases known as leukodystrophies.
A lot of the research into myelin, oligodendrocytes and the diseases caused by myelin damage uses mice as an experimental model for humans. Using mice for this type of research is appropriate because of the ethical and technical limitations of experiments on humans. This approach can be highly effective because mice and humans share a large proportion of their genes. However, there are many obvious physical differences between the two species, making it important to determine whether the results of experiments performed in mice are applicable to humans. To do this, it is necessary to understand how myelin differs between these two species at the molecular level.
Gargareta, Reuschenbach, Siems, Sun et al. approached this problem by studying the proteins found in myelin isolated from the brains of people who had passed away and donated their organs for scientific research. They used a technique called mass spectrometry, which identifies molecules based on their weight, to produce a list of proteins in human myelin that could then be compared to existing data from mouse myelin. This analysis showed that myelin is very similar in both species, but some proteins only appear in humans or in mice. Gargareta, Reuschenbach, Siems, Sun et al. then compared which genes are turned on in the oligodendrocytes making the myelin. The results of this comparison reflected most of the differences and similarities seen in the myelin proteins.
Despite the similarities identified by Gargareta, Reuschenbach, Siems, Sun et al., it became evident that there are unexpected differences between the myelin of humans and mice that will need to be considered when applying results from mice research to humans. To enable this endeavor, Gargareta, Reuschenbach, Siems, Sun et al. have created a searchable web interface of the proteins in myelin and the genes expressed in oligodendrocytes in the two species.
