Skeletal Muscle Denervation: Past, Present and Future

Kostrominova, Tatiana Y.

doi:10.3390/ijms23147489

Cited by 16 publications

(5 citation statements)

References 18 publications

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“…Skeletal muscle innervation comprises stable and functional nerve interactions with muscles, which is critical for the maintenance of normal muscle structure and function ( Kostrominova, 2022 ). Loss of motor innervation may induce rapid skeletal muscle fiber degeneration, causing muscle atrophy and fibrosis, which was verified using histopathological analysis in our study ( Supplementary Figure 2 ).…”

Section: Discussionmentioning

confidence: 99%

The profiles and clinical significance of extraocular muscle-expressed lncRNAs and mRNAs in oculomotor nerve palsy

Wu,

Shi,

Liang

et al. 2023

Front. Mol. Neurosci.

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IntroductionOculomotor nerve palsy (ONP) arises from primary abnormalities in the central neural pathways that control the extraocular muscles (EOMs). Long non-coding RNAs (lncRNAs) have been found to be involved in the pathogenesis of various neuroparalytic diseases. However, little is known about the role of lncRNAs in ONP.MethodsWe collected medial rectus muscle tissue from ONP and constant exotropia (CXT) patients during strabismus surgeries for RNA sequencing analysis. Differentially expressed mRNAs and lncRNAs were revealed and included in the functional enrichment analysis. Co-expression analysis was conducted between these differentially expressed mRNAs and lncRNAs, followed by target gene prediction of differentially expressed lncRNAs. In addition, lncRNA-microRNA and lncRNA-transcription factor-mRNA interaction networks were constructed to further elaborate the pathological changes in medial rectus muscle of ONP. Furthermore, RT-qPCR was applied to further validate the expression levels of important lncRNAs and mRNAs, whose clinical significance was examined by receiver operating characteristic (ROC) curve analysis.ResultsA total of 618 differentially expressed lncRNAs and 322 differentially expressed mRNAs were identified. The up-regulated mRNAs were significantly related to cholinergic synaptic transmission (such as CHRM3 and CHRND) and the components and metabolism of extracellular matrix (such as CHI3L1 and COL19A1), while the down-regulated mRNAs were significantly correlated with the composition (such as MYH7 and MYL3) and contraction force (such as MYH7 and TNNT1) of muscle fibers. Co-expression analysis and target gene prediction revealed the strong correlation between MYH7 and NR_126491.1 as well as MYOD1 and ENST00000524479. Moreover, the differential expressions of lncRNAs (XR_001739409.1, NR_024160.1 and XR_001738373.1) and mRNAs (CDKN1A, MYOG, MYOD1, MYBPH, TMEM64, STATH, and MYL3) were validated by RT-qPCR. ROC curve analysis showed that lncRNAs (XR_001739409.1, NR_024160.1, and NR_002766.2) and mRNAs (CDKN1A, MYOG, MYOD1, MYBPH, TMEM64, and STATH) might be promising biomarkers of ONP.ConclusionsThese results may shed light on the molecular biology of EOMs of ONP, as well as the possible correlation of lncRNAs and mRNAs with clinical practice.

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Section: Discussionmentioning

confidence: 99%

The profiles and clinical significance of extraocular muscle-expressed lncRNAs and mRNAs in oculomotor nerve palsy

Wu,

Shi,

Liang

et al. 2023

Front. Mol. Neurosci.

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“…Motor nerve denervation results in a series of degenerative processes including Wallerian degeneration, degenerative fibrosis, and muscle atrophy over a few years. 1,2 Denervation-induced muscle atrophy leads to variable degrees of functional and aesthetic deterioration, such as weakened muscle tone, eyelid descent, dry eye, changes in pretarsal fullness and convexity, and others. Although the eyelid malposition may be overcome by lateral canthal supporting procedures or the symptoms and signs of malposition may be mild enough to be accepted, the weakened muscle tone and changed pretarsal contour will last a lifetime.…”

Section: Discussionmentioning

confidence: 99%

“…Preservation of preoperative muscle tone is essential for a successful lower blepharoplasty. When the pretarsal orbicularis oculi muscle is denervated during surgery, it eventually atrophies, 1,2 which leads to eyelid malposition and loss of natural pretarsal convexity. 3,4 Pretarsal atrophy may appear variably from slight scleral show to symptomatic ectropion, according to the affected muscle part.…”

mentioning

confidence: 99%

Avoiding Pretarsal Denervation in Lower Blepharoplasty Incisions: Refined Pretarsal Motor Nerve Anatomy

Choi

Kim

2023

Plastic &Amp; Reconstructive Surgery

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Background: Pretarsal atrophy is not uncommonly found in patients who have undergone a transcutaneous or transconjunctival lower blepharoplasty due to intraoperative denervation of the pretarsal orbicularis oculi. The motor supplying concept to the lower eyelid was recently updated, however, there have not yet been any guidelines to preserve motor nerves in lower blepharoplasty incisions based on the refined knowledge. Methods: 46 fresh cadaveric hemifaces were examined to find a safe zone for a lower blepharoplasty muscle incision and a danger zone for an infraorbital incision in the transblepharoplasty midface approach. Additionally, practical anatomy about the pretarsal motor supply was also investigated in detail. Results: The medial, lateral, superior, and inferior borders of the safe zone for a lower blepharoplasty muscle incision were 9.4 mm from the medial canthus line, 3 mm from the lateral canthal crease, and 6.0 and 6.5 mm from the eyelid margin, respectively. The danger zone for an infraorbital incision ranged from 9.4 mm medial to the midpupillary line to 9.7 mm lateral to the midpupillary line. The motor nerve in the danger zone abutted the distal roof of the preseptal pocket making it vulnerable to electrocautery heat. Motor nerve distribution of the lower pretarsal orbicularis oculi was fully identified. Conclusion: There is a safe zone for the lower blepharoplasty muscle incision which if adhered to will preserve the pretarsal motor supply and prevent muscle atrophy. There is an infraorbital danger zone, where surgeons should pay special attention to avoid electrocautery heat injury.

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“…The rate of human peripheral nerve regeneration is slow; approximately 1 inch per month [ 22 ]. As a result, skeletal muscle fibers remain denervated for long periods of time, leading to activation of atrophy related pathways, muscle wasting and ultimately loss of muscle function [ 23 ]. In fact, molecular changes in muscle function can be observed within a few hours of injury and denervation [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

Skeletal muscle reprogramming enhances reinnervation after peripheral nerve injury

Personius,

Mehrotra,

Jablonski

et al. 2024

Preprint

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Peripheral Nerve Injuries (PNI) affect more than 20 million Americans and severely impact quality of life by causing long-term disability. The onset of PNI is characterized by nerve degeneration distal to the nerve injury resulting in long periods of skeletal muscle denervation. During this period, muscle fibers atrophy and frequently become incapable of “accepting” innervation because of the slow speed of axon regeneration post injury. We hypothesize that reprogramming the skeletal muscle to an embryonic-like state may preserve its reinnervation capability following PNI. To this end, we generated a mouse model in which NANOG, a pluripotency-associated transcription factor can be expressed locally upon delivery of doxycycline (Dox) in a polymeric vehicle. NANOG expression in the muscle upregulated the percentage of Pax7+ nuclei and expression of eMYHC along with other genes that are involved in muscle development. In a sciatic nerve transection model, NANOG expression led to upregulation of key genes associated with myogenesis, neurogenesis and neuromuscular junction (NMJ) formation, and downregulation of key muscle atrophy genes. Further, NANOG mice demonstrated extensive overlap between synaptic vesicles and NMJ acetylcholine receptors (AChRs) indicating restored innervation. Indeed, NANOG mice showed greater improvement in motor function as compared to wild-type (WT) animals, as evidenced by improved toe-spread reflex, EMG responses and isometric force production. In conclusion, we demonstrate that reprogramming the muscle can be an effective strategy to improve reinnervation and functional outcomes after PNI.

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Skeletal Muscle Denervation: Past, Present and Future

Abstract: This Special Issue presents some of the most recent studies on the skeletal muscle denervation [...]

Cited by 16 publications

References 18 publications

The profiles and clinical significance of extraocular muscle-expressed lncRNAs and mRNAs in oculomotor nerve palsy

The profiles and clinical significance of extraocular muscle-expressed lncRNAs and mRNAs in oculomotor nerve palsy

Avoiding Pretarsal Denervation in Lower Blepharoplasty Incisions: Refined Pretarsal Motor Nerve Anatomy

Skeletal muscle reprogramming enhances reinnervation after peripheral nerve injury

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