By Alice de Bernardy
Myelin insulates neurons and enable a faster nerve conduction across the nervous system. This quite simplistic and straight forward definition presents myelin as an accessory helping us “think fast”. But Myelin’s fundamental role in health and implication in diseases presents it as a major regulator of nervous system integrity and fundamental for normal nerve conduction.
Myelin is made of layers of cell membrane wrapped many times around axons of neurons1. This sheath enables a faster nerve conduction in the white matter since the electrical message travelling along the axon and through synapses jumps over the protective membrane and progresses at a higher pace by inducing depolarisation of the neuron membrane at the nodes of Ranvier which are rich in Sodium and Potassium channels. The insulation provided by oligodendrocytes in the brain and spinal cord, and by Schwan cell in the periphery are important modulators of the nervous system not only because myelin enables a fast conduction of messages, but because it is also crucial to maintain axon integrity and health, as well as mediating interactions between neurons and glial cells, ensuring the overall health and integrity of the nervous system1. Therefore, when regulated, myelin can be linked to many diseases.
The process of myelination occurs during the end of development and continues after birth mainly during the first year but also throughout life, as myelin plasticity has been seen to occur to repair injured tissues or even to reinforce neuronal signalling when learning2.
Factors dysregulating myelin dynamics or progressive loss of myelin can occur due to environmental factors, damaging the sheath, or to genetical defects preventing proper myelination of the tracts. Hypomyelination leads to a slower nerve conduction, and symptoms can include loss of reflexes and sensory sensations, which depends on which nerves are affected, dysautonomia which can also occur when the integrity of the autonomic nervous system is compromised. And as another example, if the upper motor neuron is damaged, exaggerated reflexes can occur due to other tracts taking over. But the loss of myelin doesn’t only reduces nerve conduction, as previously describes, the sheath has a protective role. Therefore, when this protection is loss, axons degenerate which leads to impairments gradually increasing and symptoms worsening.
The most common example when talking about demyelinating diseases3 is multiple sclerosis, designating autoimmune inflammatory diseases of the Central nervous system. Immune cells such as B and T cells invade the CNS and attack the body’s own cells, targeting myelin sheaths and creating vacuoles, leading to a process called spongiform degeneration. This is then followed by degeneration of the axon. Many different reasons can be at the origin of the inflammation, such as environmental factors like Epstein Barr virus infection. While some factors can come from genetics such as mutation in the proteolipid protein (plp) gene leading to a failure of myelin development in the CNS. Other than multiple sclerosis, chronic inflammation, such as caused by infection by the papovavirus4 can transform the nervous system in an unfavourable environment for maintenance of myelination levels. Non inflammatory causes for demyelination comprise stress, such as hypoxia or compression as seen in cases of neuralgia4.
The crucial role of myelin for maintaining the nervous system is also demonstrated as occasionally glial tumours surround themselves with zones of demyelination, creating a favourable environment for tumour proliferation and reversibly as demyelination could promote tumorigenesis3.
Overall, different well-known roles of myelin and diseases demonstrate efficiently the necessity of healthy myelination of white matter tracts to ensure cognitive capabilities. Emerging research also linked dysregulated myelin dynamics and psychiatric disorders such as schizophrenia and bipolar disorder5. In post-mortem brains of schizophrenic patients, oligodendrocytes showed structural defects and high levels of cell death, via necrosis and apoptosis, which was also linked to lowered levels of myelin in different brain regions. Aberrantly myelinated white matter tracts would contribute to the asynchrony in firing or neurons, leading to aberrant higher-level function and psychotic episodes as seen in patients due to a lack of proper coordination between brain regions. Those findings are associated to the disconnection hypothesis in mental disorders5. More research is still needed to determine the exact correlation and if myelin dysregulation would be a cause or consequence of those diseases. But overall, identification of molecular targets related to myelin health could be targeted as potential therapies for such heavy disabilities.
References:
1. Brady S, Siegel G, Albers RW. Basic Neurochemistry : Principles of Molecular, Cellular, and Medical Neurobiology. San Diego: Elsevier Science & Technology; 2011.
2. Gibson EM, Geraghty AC, Monje M. Bad wrap: Myelin and myelin plasticity in health and disease. Dev Neurobiol [Internet]. 2018 [cited 2022 May 21];78(2):123–35. Available from: http://dx.doi.org/10.1002/dneu.22541
3. Duncan ID, Radcliff AB. Inherited and acquired disorders of myelin: The underlying myelin pathology. Exp Neurol [Internet]. 2016 [cited 2022 May 21];283(Pt B):452–75. Available from: http://dx.doi.org/10.1016/j.expneurol.2016.04.002
4. Love S. Demyelinating diseases. J Clin Pathol [Internet]. 2006 [cited 2022 May 21];59(11):1151–9. Available from: http://dx.doi.org/10.1136/jcp.2005.031195
5. Valdés-Tovar M, Rodríguez-Ramírez AM, Rodríguez-Cárdenas L, Sotelo-Ramírez CE, Camarena B, Sanabrais-Jiménez MA, et al. Insights into myelin dysfunction in schizophrenia and bipolar disorder. World J Psychiatry [Internet]. 2022 [cited 2022 Jun 3];12(2):264–85. Available from: https://www.wjgnet.com/2220-3206/full/v12/i2/264.htm
Article written in June, 2022
Imperial Bioscience Review 