Vertebrate neuromuscular junctions are highly stable synapses, retaining the morphology they achieve in early postnatal development throughout most of life. However, these synapses undergo dramatic change during aging. The acetylcholine receptors (AChRs) from smooth gutters into fragmented islands, and nerve terminals similarly to be varicosities apposed islands. These changes have been attributed a slow deterioration mechanisms maintaining synapse. We used repeated, vital imaging...

Clinical trials delivering high doses of adeno-associated viruses (AAVs) expressing truncated dystrophin molecules (microdystrophins) are underway for Duchenne muscular dystrophy (DMD). We examined the efficiency and efficacy this strategy with 4 microdystrophin constructs (3 in clinical a variant largest construct), severe mouse model DMD, using AAV comparable those trials. achieved levels expression striated muscles cardiac approximately 10-fold higher than that observed skeletal muscle....

The competitive processes that result in elimination/pruning of developing synapses are incompletely understood. Serial electron microscopy was used to image postnatal mouse neuromuscular junctions where elimination is well studied and events at every synaptic contact can be examined. Glial or Schwann cells (SCs) shown have two activities during elimination: their separate nerve terminals from each other the muscle fiber; they plaque acetylcholine receptors, apposing this surface as closely...

Significance Refinement of synaptic connections occurs throughout the nervous system and is essential for its proper function. Significant gaps remain in our understanding mechanisms that mediate pruning connections—a form plasticity known as synapse elimination. Recently it has become clear there significant glial cell involvement. The present study rodent neuromuscular junction addresses two outstanding questions involving this involvement: which molecules determine Schwann behavior during...

Abstract The muscular dystrophy X-linked mouse ( mdx ) is the most commonly used preclinical model for Duchenne dystrophy. Although disease progression in does not perfectly human disease, it shares many pathological features. Early characterizations of reported severe pathology through early adulthood followed by stabilization. As a result, research has largely focused on adulthood. overarching goal this study to improve understanding tracking features throughout life. We performed thorough...

Mice lacking the sarcolemmal protein dystrophin, designated mdx, have been widely used as a model of Duchenne muscular dystrophy. Dystrophic mdx mice they mature develop notable morphological abnormalities to their neuromuscular junctions, peripheral cholinergic synapses responsible for activating muscle fibers. Most obviously acetylcholine receptor aggregates are fragmented into small non-continuous, islands. This contrasts with wild type whose continuous and pretzel-shaped in appearance....

Successful CRISPR/Cas9-based gene editing in skeletal muscle is dependent on efficient propagation of Cas9 to all myonuclei the myofiber. However, nuclear-targeted therapy cargos are strongly restricted their myonuclear domain origin. By screening nuclear localization signals and export signals, we identify “Myospreader,” a combination short peptide sequences that promotes propagation. Appending Myospreader enhances protein stability myoblasts myofibers. AAV-delivered dCas9 better inhibits...

The key to successful treatment of OSAS is individually tailor such treatment. Thus, it very important determine the severity OSAS, its pattern, and extent collapse, by gender, age, BMI.The objective study was understand characteristics obstructive sleep apnea in postmenopausal women comparing premenopausal subjects, men, using DISE. We hope that our work will help medical community consult on, diagnose, treat more effectively.A total 273 patients (195 males 78 females) diagnosed with were...

Skeletal muscle fibers are multinucleated cellular giants formed by the fusion of mononuclear myoblasts. Several molecules involved in myoblast have been discovered, and finger-like projections coincident with also implicated process. The role these cell was investigated herein. We demonstrate that filopodia generated class X myosin (Myo10), an unconventional motor protein specialized for filopodia. further show Myo10 is highly expressed differentiating myoblasts, ablation inhibits both...

In order to develop novel, effective therapies for central nervous system regeneration, it is essential better understand the role of neurotrophic factors and design, accordingly, artificial scaffolds support both neurite outgrowth synapse formation. Both nerve growth factor brain-derived are major in neural survival, development, synaptogenesis, synaptic connectivity primary cultured neurons. As a prime candidate coating material such cultures, carbon nanotubes offer unique structural,...

Exposure to the underwater environment for occupational or recreational purposes is increasing. As estimated, there are around 7 million divers active worldwide and 300,000 more in Korea. The hyperbaric presents a number of risks diver. Injuries from these hazards include barotrauma, decompression sickness, toxic effects gases, drowning, hypothermia, dangerous marine animals. For reasons, primary care physicians should understand diving related injuries assessment fitness dive. However, most...

Abstract Agrin is a motoneuron‐derived factor that initiates neuromuscular synapse formation; however, the signaling pathway underlying postsynaptic differentiation not yet understood. We have investigated role of calcium in agrin through MuSK receptor tyrosine kinase and intracellular cascade leads to AChR phosphorylation clustering. find agrin‐ neuramindase‐induced activation cultured myotubes completely blocked by removal extracellular calcium, but only slightly reduced clamping...

Hand, foot, and mouth disease (HFMD) is an acute, mostly self-limiting infection. Patients usually recover without any sequelae. However, a few cases are life threatening, especially those caused by enterovirus 71 (EV71). A 12-month-old boy was admitted to primary hospital with high fever vesicular lesions of the mouth, hands, feet. After 3 days, he experienced seizure episodes referred our hospital. On admission, conscious his chest radiograph normal. 6 hours later, suddenly lost...

Abstract Schwann cells (SCs) are integral to the formation and function of peripheral nervous system (PNS). Exemplifying their importance, loss or dysfunction SCs is a feature myriad diseases conditions that compromise PNS. Thus, it remains essential understand rules govern proliferation, differentiation reconnection with axons. Here, we examined consequences locally acutely ablating terminal (tSCs) at adult mouse neuromuscular junction (NMJ) by using mice expressing diphtheria toxin...

The arrangement of myonuclei in skeletal muscle tissue has long been used as a biomarker for health, but there is dearth vivo exploration potential effects myonuclear organization on the function and regeneration because traditional nuclear stains are performed postmortem tissue. Therefore, we sought transgenic method to produce selective persistent label whole muscles living mice. We bred together mouse line with fiber-selective expression Cre recombinase second Cre-inducible fluorescently...

Abstract The emergence of a mature nervous system requires significant refinement the synaptic connections initially formed during development. Redundant are removed in process known as synapse elimination. Synapse elimination has been extensively studied at rodent neuromuscular junction (NMJ). Although several axons converge onto each postsynaptic muscle fiber, all redundant inputs early postnatal development until single motor neuron innervates NMJ. Neuronal activity well glia influence...

The potential use of the D2.mdx mouse (the mdx mutation on DBA/2J genetic background) as a preclinical model cardiac aspects Duchenne muscular dystrophy (DMD) has been criticized based speculation that background displays an inherent hypertrophic cardiomyopathy (HCM) phenotype. Accordingly, goal current study was to further examine status this strain over 12-month period determine if observable signs HCM develop, including histopathology and pathological enlargement myocardium. Previous...

Abstract Background There is increasing evidence of crosstalk between organs. The neuromuscular junction (NMJ) a peripheral chemical synapse whose function and morphology are sensitive to acetylcholine (ACh) release muscle depolarization. In an attempt improve our understanding NMJ plasticity crosstalk, the effects unilateral direct electrical stimulation hindlimb on were investigated in rats exposed long‐term post‐synaptic blockade. Methods Sprague Dawley subjected blockade transmission by...