Myelination and myelin sheath remodelling in normal and pathological PNS nerve fibres

Hildebrand, Claes; Bowe, Constance M.; Remahl, Ingela Nilsson

doi:10.1016/0301-0082(94)90010-8

Cited by 71 publications

(43 citation statements)

References 173 publications

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“…For remyelination, we quantified g ratios ranging from 0.4 to greater than 0.85, where 0.7 is the optimal myelin thickness for nerve conduction (29). Compared with injured WT nerves, we found that the g ratios in crushed αBC −/− mice were skewed toward higher values ( Fig.…”

Section: Sensory and Motor Behaviors Are Impaired In αBcmentioning

confidence: 98%

AlphaB-crystallin regulates remyelination after peripheral nerve injury

Lim

Nakanishi

Hoghooghi

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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AlphaB-crystallin (αBC) is a small heat shock protein that is constitutively expressed by peripheral nervous system (PNS) axons and Schwann cells. To determine what role this crystallin plays after peripheral nerve damage, we found that loss of αBC impaired remyelination, which correlated with a reduced presence of myelinating Schwann cells and increased numbers of nonmyelinating Schwann cells. The heat shock protein also seems to regulate the cross-talk between Schwann cells and axons, because expected changes in neuregulin levels and ErbB2 receptor expression after PNS injury were disrupted in the absence of αBC. Such dysregulations led to defects in conduction velocity and motor and sensory functions that could be rescued with therapeutic application of the heat shock protein in vivo. Altogether, these findings show that αBC plays an important role in regulating Wallerian degeneration and remyelination after PNS injury.T he robust regenerative capacity of the damaged peripheral nervous system (PNS) is partly determined by cellular and molecular events that occur in the nerve segment distal to the injury site (1). For instance, during Wallerian degeneration, influx of calcium into the damaged nerve within 12-24 h of PNS injury activates proteases (2) that result in cytoskeletal breakdown and subsequent disintegration of the axon membrane. This axon degeneration is then followed by breakdown of the myelin sheath within 2 d (3). Schwann cells, the glial cells that characterize the PNS, subsequently undergo a number of reactive physiological changes that benefit the damaged axon. Within 48 h of peripheral nerve damage, myelinating Schwann cells decrease their expression of myelin proteins, such as myelin basic protein (MBP), peripheral myelin protein 22, and protein 0 (P0) (4), and along with their nonmyelinating counterparts, revert to a nonmyelinating phenotype (4). At ∼3-4 d postinjury, the dedifferentiated Schwann cells proliferate (5-7) and align within the basal lamina to form bands of Büngner that provide a structural and trophic supportive substrate for regenerating axons. These Schwann cells secrete neurotrophic factors that provide trophic sustenance to damaged neurons until they reestablish contact with their targets (8) and produce extracellular matrix molecules that encourage and guide outgrowing axons (9), whereas secretion of chemokines is thought to mediate the infiltration of blood-derived macrophages, which along with Schwann cells, phagocytose myelin debris and its associated axon growth inhibitors (9). Finally, based on the level of neuregulin 1 Types I and III on Schwann cells and axons, respectively, and their binding to their cognate receptors ErbB2/ ErbB3 on Schwann cells, these glia will revert to a myelinating or ensheathing phenotype on contact with regrowing axons (10). Altogether, these morphological and physiological changes in Schwann cells create an environment that encourages longdistance axon growth.In humans, however, regrowth of damaged peripheral nerves is often incomplete, wh...

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Section: Sensory and Motor Behaviors Are Impaired In αBcmentioning

confidence: 98%

AlphaB-crystallin regulates remyelination after peripheral nerve injury

Lim

Nakanishi

Hoghooghi

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…Axonal contact stimulates the differentiation of Schwann cells, perhaps in part through elevation of intracellular cAMP levels (Morgan et al 1991; for review see Mezei 1993). After rapid prolifera tion and invasion of bundles of axons, myelinating Schwann cells cease cell division, then ensheathe and wrap large caliber axons (for review, see Webster 1993;Hildebrand et al 1994), whereas nonmyelinating Schwann cells associate with small caliber axons, and retain many of the characteristics of immature Schwann cells. Based on evidence from transient cotransfection and transgenic mouse studies, it has been proposed that Tst-l/Oct-6/SClP serves as a repressor of myelination in developing Schwann cells (Monuki et al 1990(Monuki et al , 1993aWeinstein et al 1995).…”

mentioning

confidence: 99%

Tst-1/Oct-6/SCIP regulates a unique step in peripheral myelination and is required for normal respiration.

Bermingham¹,

Scherer²,

O’Connell³

et al. 1996

Genes Dev.

258

246

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The terminal differentiation of myelinating glia involves complex interactions that culminate in the formation of myelin. The POU domain transcription factor Tst-l/Oct-6/SCIP is expressed transiently during myelination, and we report here that it has a critical role in this developmental process. Deletion of the Tst-l/Oct-6/SCIP gene produces a severe defect in peripheral myelination by arresting Schwann cell maturation before axonal wrapping. Unexpectedly, the activation of major myelin-specific genes appears to be unaffected by the Tst-l/Oct-6/SCIP mutation, demonstrating that multiple, independently regulated events are required for terminal differentiation of Schwann cells. In addition, aberrant differentiation and migration of specific neurons in Tst-l/Oct-6/SCIP mutant homozygotes is associated with a fatal breathing defect, providing a model for investigating the regulation of pulmonary homeostasis.

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“…The hypothesis that myelin figures represent regions of heavy membrane turnover during development (Hildebrand et al, 1994;Morara et al, 1990) or in degeneration or pathological conditions (Tanaka et al, 1988;Tani et al, 1971;Higashi, 1995;Park et al, 1999) is pertinent in the aging rat model in which chronic ethanol consumption results in dendritic regression. Dendritic regression may result in heavy membrane turnover as it involves the retraction of dendritic processes and retrieval of dendritic organelles (Chendotal and Sotelo, 1993).…”

Section: Discussionmentioning

confidence: 99%

Ethanol-related increases in degenerating bodies in the Purkinje neuron dendrites of aging rats

Dlugos

2008

Brain Research

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Chronic ethanol consumption in aging rats results in regression of Purkinje neuron (PN) dendritic arbors (Pentney, 1995), loss of synapses (Dlugos and Pentney, 1997), dilation of the smooth endoplasmic reticulum (SER), and the formation of degenerating bodies within PN dendrites (Dlugos 2006 a, b). Dilation of the SER and the formation of degenerating bodies may be a predictor of dendritic regression. Ethanol-induced effects on mitochondria may be involved as mitochondria cooperate with the SER to maintain calcium homeostasis. The purpose of this study was to determine whether degenerating body number and mitochondrial density and structure are altered by chronic ethanol treatment in PN dendrites. Male, Fischer 344 rats, 12 months of age, were fed an ethanol or pair-fed liquid diet, or rat chow for a period of 10, 20, or 40 weeks (15 rats / treatment; 45rats / treatment duration). Ethanol-fed rats received 35% of their calories as ethanol. At the end of treatment, all animals were euthanized, perfused, and tissue prepared for electron microscopy. The densities of degenerating bodies and mitochondria, mitochondrial areas, and the distance between the SER and the mitochondria were measured. Results showed that there was an ethanol-related increase in degenerating bodies compared to controls at 40 weeks. Ethanol-induced alterations to mitochondria were absent. Correlation of the present results with those of previous studies suggest that degenerating bodies may be formed from membrane re-absorption during dendritic regression or from degenerating SER whose function has been compromised by dilation.

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Myelination and myelin sheath remodelling in normal and pathological PNS nerve fibres

Cited by 71 publications

References 173 publications

AlphaB-crystallin regulates remyelination after peripheral nerve injury

AlphaB-crystallin regulates remyelination after peripheral nerve injury

Tst-1/Oct-6/SCIP regulates a unique step in peripheral myelination and is required for normal respiration.

Ethanol-related increases in degenerating bodies in the Purkinje neuron dendrites of aging rats

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