Potential Circadian Rhythms in Oligodendrocytes? Working Together Through Time

Abstract

Oligodendrocytes (OL) are the only myelinating cells of the central nervous system thus interferences, either environmental or genetic, with their maturation or function have devastating consequences. Albeit so far neglected, one of the less appreciated, nevertheless possible, regulators of OL maturation and function is the circadian cycle. Yet, disruptions in these rhythms are unfortunately becoming a common "disorder" in the today's world. The temporal patterning of behaviour and physiology is controlled by a circadian timing system based in the anterior hypothalamus. At the molecular level, circadian rhythms are generated by a transcriptional/translational feedback system that regulates transcription and has a major impact on cellular function(s). Fundamental cellular properties/functions in most cell types vary with the daily circadian cycle: OL are unlikely an exception! To be clear, the presence of circadian oscillators or the cell-specific function(s) of the circadian clock in OL has yet to be defined. Furthermore, we wish to entertain the idea of links between the "thin" evidence on OL intrinsic circadian rhythms and their interjection(s) at different stages of lineage progression as well as in supporting/regulating OL crucial function: myelination. Individuals with intellectual and developmental syndromes as well as neurodegenerative diseases present with a disrupted sleep/wake cycle; hence, we raise the possibility that these disturbances in timing can contribute to the loss of white matter observed in these disorders. Preclinical and clinical work in this area is needed for a better understanding of how circadian rhythms influence OL maturation and function(s), to aid the development of new therapeutic strategies and standards of care for these patients.

Sleep quality relates to emotional reactivity via intracortical myelination

“…For the same reason, TIV was orthogonalized to sex before inclusion in the GLMs completely removing the well-known collinearity between these two variables ( r = 0.002, p = 0.9 after orthogonalization). Finally, the inclusion of the time of day when the MRI scan took place was included to account for circadian effects on oligodendrocyte physiology and myelin production [ 37 ]. Subjects’ chronotype is not available on the HCP dataset.…”

Sleep Disorders in Relapsing-Remitting Multiple Sclerosis Patients

“…Maturation of OL depends on circadian cycle, disruption of which can be caused by SD or created artificially (common "disorder" in shift work). Neurodegenerative diseases associated with a disrupted sleep/wake cycle contribute to the volume of the white matter loss [25,36,38]. Philips T. and Rothstein J. D. reported that decreasing of sleep quality and duration has a negative influence on myelination due to OLs' dysfunction (disruption of myelin sheath and prevention of lactate transmission to axons) [24,25].…”

Circadian Variation in Efficacy of Medications

“…Finally, the preclinical and clinical studies of remyelination by oligodendrocytes for disease mitigation should take into account circadian rhythms of those cells. 168…”

“…Regardless, taken together it is apparent that treatment of MS should use a chronobiological approach, and the few clinical studies that have investigated time of day effects are very limited and grossly underpowered. Finally, the preclinical and clinical studies of remyelination by oligodendrocytes for disease mitigation should take into account circadian rhythms of those cells 168 …”