The myelin sheath a tubular case or envelope gives the whitish appearance to the white matter of the brain. Myelin cells are included in the category of Gail cells. Glial cells function to support the processes of neurons in a variety of ways.
The glial cells forming myelin sheaths are called oligodendrocytes in the central nervous system and Schwann cells in the peripheral nervous system. While the optical transparency of the larval zebrafish lends itself to non-invasive live imaging, performing such experiments in the mammalian CNS is more invasive and technically challenging. Similar techniques could be used to image superficial myelinated tracts in the spinal cord over time Locatelli et al.
One alternative is to use two-photon microendoscopy, where a microendoscope probe with a gradient refractive index GRIN lens is inserted into the tissue to image cells deeper in the brain [previously used to image CA1 neurons of the hippocampus Jung et al.
However, endoscope insertion may lead to inflammatory responses which could impact myelination. An alternative could be three-photon microscopy using the cranial imaging window method, which has also been previously used to image the hippocampus Horton et al. Three-photon microscopy gives a significantly greater signal-to-background ratio than two-photon microscopy and can therefore be used to image deeper tissue structures.
It is particularly important to consider not only different CNS regions, but different neurons within these regions. Previous research suggests that there are mechanistic differences in how distinct neuron subtypes regulate their myelination Koudelka et al.
Additionally, there may be diversity in local regulation of myelin. It is essential to remember that different parts of the CNS are not separate entities but are interconnected. Integrating mesoscale connectomics, which focuses on understanding the connections of different neuron subtypes across different regions Zeng, , will be crucial to our understanding of how lifelong myelination dynamics vary between different circuits.
What is the functional consequence of myelin regulation along distinct circuits? Thus far, the functional implications can only be inferred by correlations with behaviour. Ultimately, there is a need to couple measurement of myelin dynamics with direct assessment of circuit activity.
This will require the recording of neuronal activity during longitudinal studies of myelination in order to directly connect de novo myelination or sheath remodelling observed to changes in circuit function with time. It will be important to measure the myelin dynamics and electrophysiological activity of individual neurons and axons to determine how changes in the various myelin sheath parameters actually affects the conduction properties at the single cell level, as well as assessing activity on a population level.
The myelination of axons represents a powerful potential mechanism to regulate circuit function throughout life. Research has demonstrated that de novo myelination in the cortex via the production of new oligodendrocytes occurs even in adulthood, and that this can be enhanced by stimulating circuit activity. Once myelin has formed, it is stable with little turnover of oligodendrocytes and limited remodelling of the lengths of existing myelin sheaths.
However, these stable structures may retain the capacity to remodel if myelin is disturbed. This has interesting implications concerning the plasticity of myelin in maintaining circuit function during injury, disease, and old age. Precisely how changes in myelination affect the function of the underlying circuit remains to be seen. Ultimately, a circuit-level approach, integrating analysis of myelin dynamics with direct measurement of circuit function, is required to fully appreciate how dynamic myelination influences overall nervous system function throughout life.
All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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Individual oligodendrocytes have only a few hours in which to generate new myelin sheaths in vivo. Cell 25, — Dawson, M. NG2-expressing glial progenitor cells: an abundant and widespread population of cycling cells in the adult rat CNS. Fard, M. BCAS1 expression defines a population of early myelinating oligodendrocytes in multiple sclerosis lesions.
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In vivo mammalian brain imaging using one- and two-photon fluorescence microendoscopy. Researchers developed mouse models that had defective myelin proteins, resulting in a myelin deficiency. Loss of myelin is a problem for many CNS disorders, including stroke, spinal cord injury, and, most notably, multiple sclerosis MS.
MS is a chronic, disabling disease of the CNS that affects more than 2. MS results from the accumulation of damage to myelin and the underlying nerve fibers it insulates and protects. Current research indicates that MS involves an autoimmune response.
Scientists think that immune cells, which normally defend the body against bacteria and viruses, mistakenly attack the myelin sheath, stripping it away and exposing the nerve fibers underneath. In addition, recent research suggests that axon damage occurs early on in the course of the disease. Once damaged, the ability of nerve cells in the brain and spinal cord to communicate with each other and with muscles is compromised, leading to a variety of unpredictable symptoms that vary from person to person.
These symptoms, which can be temporary or permanent, range from fatigue, weakness, and numbness to blindness and even paralysis. Research understanding the components of myelin, how it is produced, and how it functions has paved the way for new therapeutic possibilities in myelin-degenerative diseases like MS.
Repairing and protecting myelin is one of the approaches to treating demyelinating disease like MS. This approach focuses on 1 repairing the damage that has already occurred and 2 preventing further injury to nerves and axons. Several drugs that are currently approved for treating MS follow the second strategy.
They work by suppressing or changing the activity of the immune system, protecting myelin from unwarranted attacks. However, to date none of the available medications address regeneration of lost myelin. Stem cell therapy is one avenue being explored in the search for treatments for MS. These new stem cells were then infused into the spinal cords of mice models of MS where they secreted factors that helped the myelin-producing cells survive.
Consequently, these mice had more myelination and less axonal damage compared to mice that did not receive stem cell infusions. While the results are promising, much more work will need to be done in human clinical trials to determine the therapeutic efficacy. Continued research efforts funded by public and private institutions worldwide seek to understand how myelin is compromised in diseases like MS, revealing new possibilities for treatment and offering hope to the millions of people affected by these diseases.
Her translational research focuses on molecular mechanisms of Alzheimer's disease and psychosis. In addition to contributing to BrainFacts. Ask a neuroscientist your questions about the brain. Submit a Question. See how discoveries in the lab have improved human health. Information Transmission in the Body. Figure 1. Figure Detail. Axonal Signaling Regulates Myelination.
Figure 2: The fate of demyelinated axons. The case in the CNS is illustrated. Research in Myelin Biology and Pathology. Figure 3. References and Recommended Reading Brinkmann, B. Waxman, S. The Axon: Structure, Function and Pathophysiology.
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