Shifting Paradigms of White Matter Diseases

Oligodendrocytes, the cells that make “white matter” white play an important role in conducting signals through the brain and spinal cord. The breakdown and loss of oligodendrocytes has long been implicated in demyelinating disorders, most notably multiple sclerosis (MS). However, scientists increasingly understand that oligodendrocytes dysfunction may be to blame for neuropsychological disorders such as bipolar disorder and schizophrenia.

Oligodendrocytes insulate neurons by wrapping layers of fat, or myelin, around the axons, the long processes of neurons that convey signals. A myelinated axon, thus, resembles a branch with a series of evenly spaced croissants wrapped around it. This allows a signal to jump along the spaces between the myelination instead of traveling along the entire axon. Myelination allows the neural equivalent of taking the subway instead of walking.

As oligodendrocytes play such an important role in information processing in the brain, the loss of myelination can be devastating. The most well known demyelinating disorder is MS, in which the immune system attacks oligodendrocytes and breaks down the myelin. If myelination is the neural equivalent of signals riding the subway, demyelinating disorders close the subway lines forcing passengers to walk. This then disrupts the coordination of signals sent through the brain. In MS, this results in problems with motor control and movement.

But movement is not the only brain function that requires the complex coordination of signals. The brain is constantly receiving and processing information, making decisions, and sending instructions. These processes also require the coordination inputs with appropriate decisions and actions. Furthermore, myelin is known to be intimately involved in higher brain functions like cognition and learning. As a result, scientist and neurologists have recently begun looking at the similarities between MS and other neuropsychiatric disorders such as schizophrenia and bipolar disorder. Oligodendrocyte dysfunction and a loss of white matter have been implicated in these neuropsychiatric disorders. Imaging studies have shown that patients with bipolar disorder and schizophrenia have less white matter than healthy patients. And post-mortem studies have demonstrated a cessation of development of new myelin in early adulthood in patients with bipolar disorder, compared to a steady decrease over a lifetime in healthy patients.

Although anti-psychotics have always been assumed to act on neurons, the evidence is mounting that they actually function by improving myelination. Lithium, for example, acts on a number of the pathways involved in myelination, and has even been effective in treating experimental models of MS. It seems, therefore, possible that the emotional and cognitive dysregulation in these disorders actually results from an inability of the brain to coordinate the flow of information received from the environment with the proper emotional output? If oligodendrocytes are, in fact, responsible these disorders, this could lead to additional innovative treatment strategies.

References

Emery, B. (2010). Regulation of Oligodendrocyte Differentiation and Myelination Science, 330 (6005), 779-782 DOI: 10.1126/science.1190927

Nave, K. (2010). Myelination and support of axonal integrity by glia Nature, 468 (7321), 244-252 DOI: 10.1038/nature09614

Bartzokis, G. (2012). Neuroglialpharmacology: Myelination as a shared mechanism of action of psychotropic treatments Neuropharmacology DOI: 10.1016/j.neuropharm.2012.01.015

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