Myelin plasticity in the central nervous system

Purger, David; Gibson, Elaine; Monje, Michelle

doi:10.1016/j.neuropharm.2015.08.001

Cited by 99 publications

(84 citation statements)

References 131 publications

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“…Recent studies suggest that myelination can serve as a form of plasticity to adapt brain function to environmental stimuli and that altering myelin growth to neuronally derived signals (activity or growth factor) is one potential mechanism (Fields, 2008;Makinodan et al, 2012;Mckenzie et al, 2014;Fields, 2015;Purger et al, 2015). For example, social isolation of adolescent or adult mice resulted in behavioral and cognitive dysfunction that correlated with reduced myelin gene expression and reduced myelin thickness in the prefrontal cortex, which were normalized upon social reintegration Makinodan et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Strength of ERK1/2 MAPK Activation Determines Its Effect on Myelin and Axonal Integrity in the Adult CNS

et al. 2016

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Myelin growth is a tightly regulated process driven by multiple signals. ERK1/2-MAPK signaling is an important regulator of myelin thickness. Because, in demyelinating diseases, the myelin formed during remyelination fails to achieve normal thickness, increasing ERK1/2 activity in oligodendrocytes is of obvious therapeutic potential for promoting efficient remyelination. However, other studies have suggested that increased levels of ERK1/2 activity could, in fact, have detrimental effects on myelinating cells. Because the strength, duration, or timing of ERK1/2 activation may alter the biological outcomes of cellular responses markedly, here, we investigated the effect of modulating ERK1/2 activity in myelinating cells using transgenic mouse lines in which ERK1/2 activation was upregulated conditionally in a graded manner. We found enhanced myelin gene expression and myelin growth in the adult CNS at both moderate and hyperactivated levels of ERK1/2 when upregulation commenced during developmental myelination or was induced later during adulthood in quiescent preexisting oligodendrocytes, after active myelination is largely terminated. However, a late onset of demyelination and axonal degeneration occurred at hyperelevated, but not moderately elevated, levels regardless of the timing of the upregulation. Similarly, myelin and axonal pathology occurred with elevated ERK1/2 activity in Schwann cells. We conclude that a fine tuning of ERK1/2 signaling strength is critically important for normal oligodendrocyte and Schwann cell function and that disturbance of this balance has negative consequences for myelin and axonal integrity in the long term. Therefore, therapeutic modulation of ERK1/2 activity in demyelinating disease or peripheral neuropathies must be approached with caution.

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Section: Discussionmentioning

confidence: 99%

Strength of ERK1/2 MAPK Activation Determines Its Effect on Myelin and Axonal Integrity in the Adult CNS

et al. 2016

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“…Changes in the fine structure of myelin in a neural circuit, such as alterations in sheath thickness and internode length, are expected to affect conduction velocity (Purger et al, 2016). Myelinated fibers with large diameters and thick myelin sheaths can produce more effective conduction velocities.…”

Section: Fig 4 Alteration Of the Myelin Sheaths In The Aged Rats *mentioning

confidence: 99%

Stereological Evidence for De/Re-Generation of Myelin Sheaths in Aged Brain White Matter of Female Rats

Zhang

et al. 2017

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Studies have provided qualitative evidence of de-myelination and re-myelination in aged brain white matter. However, there have been no quantitative evidences of degeneration and regeneration of myelin sheaths in white matter. The present study was designed to investigate the quantitative changes in myelin sheaths using unbiased stereological techniques and qualitative changes using electron microscopy in aged brain white matter. Results obtained showed that in brain white matter, the total volume of myelin sheaths of old-age female rats was not significantly different from that of young female rats, but the total length of myelinated fibers in old female rats was significantly decreased by 46.1% when compared with that of young female rats. Myelin sheath volume per unit length of myelinated fibers of old female rats was significantly increased by 43.4% compared with that of young female rats. The mean thickness of myelin sheaths in the white matter of the old rats was significantly increased by 33.3%, when compared with that of young female rats. In age-related loss of myelinated fibers, most fibers had diameters less than 1.4 μm, and myelin sheath thicknesses less than 0.14 μm, but the length of myelinated fibers with diameters more than 0.6 μm and myelin sheath thicknesses more than 0.22 μm increased with age. Myelinated fibers with ratios of myelin sheath thicknesses to myelinated fiber external diameter less than 0.21 were significantly lower in elderly rats than in young rats. However, the total length of myelinated fibers with ratios of myelin sheath thicknesses to myelinated fiber external diameter more than 0.23 was higher in aged rats than in young rats. About 6.58% of myelin sheaths showed degenerative alterations, while 0.88% myelin sheaths showed regenerative alterations. This study provides stereological evidence not only for degeneration but also regeneration of myelin sheaths in aged white matter.

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“…As this topic is examined in-depth in a review in this same issue (Purger et al, 2015), what follows here is a general summary of some of the highlights of the potential relationship between behavioral experiences and neuronal activity-induced changes in the oligodendrocyte lineage.…”

Section: Neural Activitymentioning

confidence: 99%

Behavioral experiences as drivers of oligodendrocyte lineage dynamics and myelin plasticity

2016

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Many behavioral experiences are known to promote hippocampal neurogenesis. In contrast, the ability of behavioral experiences to influence the production of oligodendrocytes and myelin sheath formation remains relatively unknown. However, several recent studies indicate that voluntary exercise and environmental enrichment can positively influence both oligodendrogenesis and myelination, and that, in contrast, social isolation can negatively influence myelination. In this review we summarize studies addressing the influence of behavioral experiences on oligodendrocyte lineage cells and myelin, and highlight potential mechanisms including experience-dependent neuronal activity, metabolites, and stress effectors, as well as both local and systemic secreted factors. Although more study is required to better understand the underlying mechanisms by which behavioral experiences regulate oligodendrocyte lineage cells, this exciting and newly emerging field has already revealed that oligodendrocytes and their progenitors are highly responsive to behavioral experiences and suggest the existence of a complex network of reciprocal interactions among oligodendrocyte lineage development, behavioral experiences, and brain function. Achieving a better understanding of these relationships may have profound implications for human health, and in particular, for our understanding of changes in brain function that occur in response to experiences. This article is part of the Special Issue entitled 'Oligodendrocytes in Health and Disease'.

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Myelin plasticity in the central nervous system

Cited by 99 publications

References 131 publications

Strength of ERK1/2 MAPK Activation Determines Its Effect on Myelin and Axonal Integrity in the Adult CNS

Strength of ERK1/2 MAPK Activation Determines Its Effect on Myelin and Axonal Integrity in the Adult CNS

Stereological Evidence for De/Re-Generation of Myelin Sheaths in Aged Brain White Matter of Female Rats

Behavioral experiences as drivers of oligodendrocyte lineage dynamics and myelin plasticity

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