Chronic peripheral nerve compression disrupts paranodal axoglial junctions

Otani, Yoshinori; Yermakov, Leonid M.; Dupree, Jeffrey L.; Susuki, Keiichiro

doi:10.1002/mus.25273

Cited by 15 publications

(12 citation statements)

References 47 publications

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“…Electrophysiological analysis. Motor NCVs were measured as previously described 59 with slight modifications. In brief, conduction speeds in motor nerve fibers innervating the plantar muscle was examined under anesthesia by intraperitoneal injection of anesthetic combination (0.3 mg kg −1 medetomidine, 4.0 mg kg −1 midazolam, and 5.0 mg kg −1 butorphanol).…”

Section: Methodsmentioning

confidence: 99%

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Upregulation of large myelin protein zero leads to Charcot–Marie–Tooth disease-like neuropathy in mice

et al. 2020

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Charcot-Marie-Tooth (CMT) disease is a hereditary neuropathy mainly caused by gene mutation of peripheral myelin proteins including myelin protein zero (P0, MPZ). Large myelin protein zero (L-MPZ) is an isoform of P0 that contains an extended polypeptide synthesized by translational readthrough at the C-terminus in tetrapods, including humans. The physiological role of L-MPZ and consequences of an altered L-MPZ/P0 ratio in peripheral myelin are not known. To clarify this, we used genome editing to generate a mouse line (L-MPZ mice) that produced L-MPZ instead of P0. Motor tests and electrophysiological, immunohistological, and electron microscopy analyses show that homozygous L-MPZ mice exhibit CMT-like phenotypes including thin and/or loose myelin, increased small-caliber axons, and disorganized axo-glial interactions. Heterozygous mice show a milder phenotype. These results highlight the importance of an appropriate L-MPZ/P0 ratio and show that aberrant readthrough of a myelin protein causes neuropathy.

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Section: Methodsmentioning

confidence: 99%

“…Immunofluorescence study. Immunostaining methods were modified as described previously 59 . Sciatic nerves obtained from anesthetized 10-week-old mice were rapidly dissected and immediately fixed in ice-cold 4% paraformaldehyde (PFA) in 0.1 M phosphate buffer (PB) (pH 7.4) for 30 min.…”

Section: Methodsmentioning

confidence: 99%

Upregulation of large myelin protein zero leads to Charcot–Marie–Tooth disease-like neuropathy in mice

et al. 2020

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“…Immunostaining of optic and sciatic nerve sections or teased sciatic nerves was performed as described previously ( Otani et al., 2017 ). In brief, after the completion of methylglyoxal exposure, nerves were immediately fixed in ice-cold 4% paraformaldehyde in 0.1 M phosphate buffer for 30 min, cryoprotected overnight in 20% sucrose, blocked and placed in custom-made foil blocks, and frozen in Optimal Cutting Temperature (O.C.T.)…”

Section: Methodsmentioning

confidence: 99%

Methylglyoxal Disrupts Paranodal Axoglial Junctions via Calpain Activation

et al. 2018

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Nodes of Ranvier and associated paranodal and juxtaparanodal domains along myelinated axons are essential for normal function of the peripheral and central nervous systems. Disruption of these domains as well as increases in the reactive carbonyl species methylglyoxal are implicated as a pathophysiology common to a wide variety of neurological diseases. Here, using an ex vivo nerve exposure model, we show that increasing methylglyoxal produces paranodal disruption, evidenced by disorganized immunostaining of axoglial cell-adhesion proteins, in both sciatic and optic nerves from wild-type mice. Consistent with previous studies showing that increase of methylglyoxal can alter intracellular calcium homeostasis, we found upregulated activity of the calcium-activated protease calpain in sciatic nerves after methylglyoxal exposure. Methylglyoxal exposure altered clusters of proteins that are known as calpain substrates: ezrin in Schwann cell microvilli at the perinodal area and zonula occludens 1 in Schwann cell autotypic junctions at paranodes. Finally, treatment with the calpain inhibitor calpeptin ameliorated methylglyoxal-evoked ezrin loss and paranodal disruption in both sciatic and optic nerves. Our findings strongly suggest that elevated methylglyoxal levels and subsequent calpain activation contribute to the disruption of specialized axoglial domains along myelinated nerve fibers in neurological diseases.

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“…Кроме того, исследования последних лет показали, что на молекулярном уровне при длительной компрессии нерва страдают паранодальные и юкстапаранодальные области, а миелин интернодальных областей остается неизменным [16]. Паранодальные изменения также обнаруживаются при ряде аутоиммунных нейропатий.…”

Section: Introductionunclassified

“…При компрессионных нейропатиях также страдает высокоупорядоченная структура паранодальной и юкстапаранодальной областей. Повреждаются аксо-глиальные соединения в юкстапаранодальной области, в связи с чем быстрые калиевые каналы перемещаются к перехватам Ранвье [16]. При этом миелиновая оболочка и белковые соединения интернодальных участков остаются интактными.…”

Section: Introductionunclassified

Conduction block as an electrophysiological phenomenon: a review of the literature

Никитин

Муртазина

Дружинин

2019

Neuromuscular Diseases

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Evaluation and interpretation of electrophysiological phenomena often plays an important role in the diagnosis of neuromuscular diseases. Motor nerve conduction block is a reduction of either amplitude or area of the compound motor action potential elicited by proximal to distal motor nerve stimulation. Today, the value of conduction block in the diagnosis of demyelinating and axonal neuropathies, as well as the diagnostic criteria for these disorders, are still under discussion.Objective of the review of the literature is to highlight the value of conduction block as an electrophysiological phenomenon in the light of clinical manifestations. There is no consensus in the literature which motor response parameters should be used as partial conduction block criteria. The diversity of pathogenic forms in which conduction block can be registered does not allow to consider the phenomenon as a sign of only demyelinating lesions, and the term conduction block should be considered as a pure electrophysiological phenomenon. Different pathophysiological mechanisms of conduction block formation should be studied separately within each nosology. Conduction block detection does not allow to specify a particular diagnosis, however, in conjunction with clinical and anamnestic data, it may be the main argument in the diagnosis of a number of peripheral nerves diseases.

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Chronic peripheral nerve compression disrupts paranodal axoglial junctions

Cited by 15 publications

References 47 publications

Upregulation of large myelin protein zero leads to Charcot–Marie–Tooth disease-like neuropathy in mice

Upregulation of large myelin protein zero leads to Charcot–Marie–Tooth disease-like neuropathy in mice

Methylglyoxal Disrupts Paranodal Axoglial Junctions via Calpain Activation

Conduction block as an electrophysiological phenomenon: a review of the literature

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