302 results match your criteria nmj rat

Cross-talk between motor neurons and myotubes via endogenously secreted neural and muscular growth factors.

Physiol Rep 2021 Apr;9(8):e14791

Musculoskeletal Science & Sports Medicine Research Centre, Department of Life Sciences, Manchester Metropolitan University, Manchester, UK.

Neuromuscular junction (NMJ) research is vital to advance the understanding of neuromuscular patho-physiology and development of novel therapies for diseases associated with NM dysfunction. In vivo, the micro-environment surrounding the NMJ has a significant impact on NMJ formation and maintenance via neurotrophic and differentiation factors that are secreted as a result of cross-talk between muscle fibers and motor neurons. Recently we showed the formation of functional NMJs in vitro in a co-culture of immortalized human myoblasts and motor neurons from rat-embryo spinal-cord explants, using a culture medium free from serum and neurotrophic or growth factors. Read More

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Heterologous fibrin biopolymer associated to a single suture stitch enables the return of neuromuscular junction to its mature pattern after peripheral nerve injury.

Injury 2021 Apr 17;52(4):731-737. Epub 2020 Oct 17.

Department of Structural and Functional Biology (Anatomy Sector), Institute of Biosciences, São Paulo State University (Unesp), Botucatu, São Paulo, Brazil. Electronic address:

Denervation leads to severe atrophy of neuromuscular junction (NMJ) structure including decrease of the expression of fundamental proteins. Up to now, conventional suture has been the gold standard method used to correct this injury. Fibrin sealant is one of the alternatives proposed to optimize this method. Read More

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Profiling age-related muscle weakness and wasting: neuromuscular junction transmission as a driver of age-related physical decline.

Geroscience 2021 Apr 24. Epub 2021 Apr 24.

Division of Neuromuscular Diseases, Department of Neurology, The Ohio State University Wexner Medical Center, 1060 Carmack Road, Room 207, Columbus, OH, 43210, USA.

Pathological age-related loss of skeletal muscle strength and mass contribute to impaired physical function in older adults. Factors that promote the development of these conditions remain incompletely understood, impeding development of effective and specific diagnostic and therapeutic approaches. Inconclusive evidence across species suggests disruption of action potential signal transmission at the neuromuscular junction (NMJ), the crucial connection between the nervous and muscular systems, as a possible contributor to age-related muscle dysfunction. Read More

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Bariatric surgery induces morphological changes in the extensor digitorum longus muscle in the offspring of obese rats.

Tissue Cell 2021 Mar 26;72:101537. Epub 2021 Mar 26.

Master's Program in Biosciences and Health, State University of Western Paraná (UNIOESTE), Cascavel, PR, Brazil.

Introduction: The effects of the maternal nutritional environment on the growth and metabolism of the offspring, and its impacts on health in adult life are defined as metabolic programming. Thus, the objective of this study was to evaluate the effects of Roux-en-Y gastric bypass (RYGB) on the morphology of muscle fiber and neuromuscular junction (NMJ) of the offspring of rats submitted to RYGB.

Methods: Three-week-old Wistar rats were separated into two groups: 1) CAF SHAM which received a cafeteria diet and was submitted to a sham operation and 2) CAF RYGB, which received a cafeteria diet and was submitted to RYGB. Read More

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Secondary Denervation is a Chronic Pathophysiologic Sequela of Volumetric Muscle Loss.

J Appl Physiol (1985) 2021 Apr 8. Epub 2021 Apr 8.

School of Kinesiology, University of Minnesota, United States.

Volumetric muscle loss (VML) is the traumatic loss of muscle tissue that results in long-term functional impairments. Despite the loss of myofibers, there remains an unexplained significant decline in muscle function. VML injury likely extends beyond the defect area, causing negative secondary outcomes to the neuromuscular system, including the neuromuscular junctions (NMJs), yet the extent to which VML induces denervation is unclear. Read More

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Pelvic floor muscle function recovery using biofabricated tissue constructs with neuromuscular junctions.

Acta Biomater 2021 02 13;121:237-249. Epub 2020 Dec 13.

Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1094, USA. Electronic address:

Damages in pelvic floor muscles often cause dysfunction of the entire pelvic urogenital system, which is clinically challenging. A bioengineered skeletal muscle construct that mimics structural and functional characteristics of native skeletal muscle could provide a therapeutic option to restore normal muscle function. However, most of the current bioengineered muscle constructs are unable to provide timely innervation necessary for successful grafting and functional recovery. Read More

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February 2021

Evidence That the Central Nervous System Can Induce a Modification at the Neuromuscular Junction That Contributes to the Maintenance of a Behavioral Response.

J Neurosci 2020 11 23;40(48):9186-9209. Epub 2020 Oct 23.

Department of Psychological and Brain Sciences, Texas A&M University, College Station, Texas 77843

Neurons within the spinal cord are sensitive to environmental relations and can bring about a behavioral modification without input from the brain. For example, rats that have undergone a thoracic (T2) transection can learn to maintain a hind leg in a flexed position to minimize exposure to a noxious electrical stimulation (shock). Inactivating neurons within the spinal cord with lidocaine, or cutting communication between the spinal cord and the periphery (sciatic transection), eliminates the capacity to learn, which implies that it depends on spinal neurons. Read More

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November 2020

Functional characterization of extrinsic tongue muscles in the Pink1-/- rat model of Parkinson disease.

PLoS One 2020 16;15(10):e0240366. Epub 2020 Oct 16.

Department of Surgery, University of Wisconsin, Madison, Wisconsin, United States of America.

Parkinson disease (PD) is associated with speech and swallowing difficulties likely due to pathology in widespread brain and nervous system regions. In post-mortem studies of PD, pathology has been reported in pharyngeal and laryngeal nerves and muscles. However, it is unknown whether PD is associated with neuromuscular changes in the tongue. Read More

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December 2020

A Novel Bioengineered Functional Motor Unit Platform to Study Neuromuscular Interaction.

J Clin Med 2020 Oct 10;9(10). Epub 2020 Oct 10.

Musculoskeletal Science & Sports Medicine Research Centre, Department of Life Sciences, Manchester Metropolitan University, Manchester M1 5GD, UK.

Background: In many neurodegenerative and muscular disorders, and loss of innervation in sarcopenia, improper reinnervation of muscle and dysfunction of the motor unit (MU) are key pathogenic features. studies of MUs are constrained due to difficulties isolating and extracting functional MUs, so there is a need for a simplified and reproducible system of engineered MUs.

Objective: to develop and characterise a functional MU model , permitting the analysis of MU development and function. Read More

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October 2020

Combination of acamprosate and baclofen (PXT864) as a potential new therapy for amyotrophic lateral sclerosis.

J Neurosci Res 2020 12 19;98(12):2435-2450. Epub 2020 Aug 19.

PHARNEXT, Paris, 75009, France.

There is currently no therapy impacting the course of amyotrophic lateral sclerosis (ALS). The only approved treatments are riluzole and edaravone, but their efficacy is modest and short-lasting, highlighting the need for innovative therapies. We previously demonstrated the ability of PXT864, a combination of low doses of acamprosate and baclofen, to synergistically restore cellular and behavioral activity in Alzheimer's and Parkinson's disease models. Read More

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December 2020

Effects of Vocal Training on Thyroarytenoid Muscle Neuromuscular Junctions and Myofibers in Young and Older Rats.

J Gerontol A Biol Sci Med Sci 2021 Jan;76(2):244-252

Department of Otolaryngology-Head and Neck Surgery, NYU Langone Health, New York, New York.

The purpose of this investigation was to determine the effects of vocal training on neuromuscular junction (NMJ) morphology and muscle fiber size and composition in the thyroarytenoid muscle, the primary muscle in the vocal fold, in younger (9-month) and older (24-month) Fischer 344 × Brown Norway male rats. Over 4 or 8 weeks of vocal training, rats of both ages progressively increased their daily number of ultrasonic vocalizations (USVs) through operant conditioning and were then compared to an untrained control group. Neuromuscular junction morphology and myofiber size and composition were measured from the thyroarytenoid muscle. Read More

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January 2021

Is Innervation of the Neuromuscular Junction at the Diaphragm Modulated by sGC/cGMP Signaling?

Front Physiol 2020 23;11:700. Epub 2020 Jun 23.

Institute of Neurobiology, Biomedical Research Center of the Slovak Academy of Sciences, Košice, Slovakia.

We previously reported NO/sGC signaling in the upper respiratory pathway, receiving input from the respiratory neurons of the brainstem to phrenic motoneurons in the C3-C6 spinal cord. In order to assess whether innervation of the neuromuscular junction (NMJ) at the diaphragm is modulated by sGC/cGMP signaling, we performed unilateral 8-day continuous ligation of the phrenic nerve in rats. We examined sGCβ1 within the lower bulbospinal pathway (phrenic motoneurons, phrenic nerves and NMJs at the diaphragm) and the cGMP level in the contra- and ipsilateral hemidiaphragm. Read More

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Synergistic PXT3003 therapy uncouples neuromuscular function from dysmyelination in male Charcot-Marie-Tooth disease type 1A (CMT1A) rats.

J Neurosci Res 2020 10 26;98(10):1933-1952. Epub 2020 Jun 26.

Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Göttingen, Germany.

Charcot-Marie-Tooth disease 1 A (CMT1A) is caused by an intrachromosomal duplication of the gene encoding for PMP22 leading to peripheral nerve dysmyelination, axonal loss, and progressive muscle weakness. No therapy is available. PXT3003 is a low-dose combination of baclofen, naltrexone, and sorbitol which has been shown to improve disease symptoms in Pmp22 transgenic rats, a bona fide model of CMT1A disease. Read More

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October 2020

Cinnamyl Sulfonamide Hydroxamate Derivatives Inhibited LPS-Stimulated NF-kB Expression in RAW 264.7 Cells and Mitigated Experimental Colitis in Wistar Rats .

Curr Pharm Des 2020 ;26(38):4934-4943

Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka-576104, India.

Background: Histone deacetylase (HDAC) inhibition has been found to be effective in the treatment of inflammatory bowel disease. Previous studies have reported that Cinnamyl sulfonamide hydroxamate derivatives possess non-selective HDAC inhibition.

Objective: The present study was designed to screen three selected Cinnamyl sulfonamide hydroxamate derivatives, NMJ-1, NMJ-2, and NMJ3, for in vitro anti-inflammatory response by assessing the expression of pNF-κB in lipopolysaccharide (LPS)-induced inflammatory changes on RAW 264. Read More

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Reaching task performance is associated to neuromuscular junction adaptations in rats with induced diabetes mellitus.

Braz J Med Biol Res 2020 3;53(7):e8763. Epub 2020 Jun 3.

Departamento de Fisioterapia, Universidade Federal de São Carlos, São Carlos, SP, Brasil.

Upper limb performance is affected by diabetes mellitus (DM). Neuromuscular junction (NMJ) is a key structure to understand the relationship between performance and morphology in DM. The aim of the study was to analyze NMJ plasticity due to DM in an animal model and its relationship with the function of forelimbs in rats. Read More

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Neutralizing BDNF and FGF2 injection into denervated skeletal muscle improve recovery after nerve repair.

Muscle Nerve 2020 09 18;62(3):404-412. Epub 2020 Jun 18.

Department of Anatomy I, University of Cologne, Germany.

Background: After facial nerve injury and surgical repair in rats, recovery of vibrissal whisking is associated with a high proportion of mono-innervated neuro-muscular junctions (NMJs). Our earlier work with Sprague Dawley (SD)/Royal College of Surgeons (RCS) rats, which are blind and spontaneously restore NMJ-monoinnervation and whisking, showed correlations between functional recovery and increase of fibroblast growth factor-2 (FGF2) and brain-derived neurotrophic factor (BDNF) in denervated vibrissal muscles.

Methods: We used normally sighted rats (Wistar), in which NMJ-polyinnervation is highly correlated with poor whisking recovery, and injected the vibrissal muscle levator labii superioris (LLS) with combinations of BDNF, anti-BDNF, and FGF2 at different postoperative periods after facial nerve injury. Read More

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September 2020

Site-directed MT1-MMP trafficking and surface insertion regulate AChR clustering and remodeling at developing NMJs.

Elife 2020 03 24;9. Epub 2020 Mar 24.

School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.

At vertebrate neuromuscular junctions (NMJs), the synaptic basal lamina contains different extracellular matrix (ECM) proteins and synaptogenic factors that induce and maintain synaptic specializations. Here, we report that podosome-like structures (PLSs) induced by ubiquitous ECM proteins regulate the formation and remodeling of acetylcholine receptor (AChR) clusters via focal ECM degradation. Mechanistically, ECM degradation is mediated by PLS-directed trafficking and surface insertion of membrane-type 1 matrix metalloproteinase (MT1-MMP) to AChR clusters through microtubule-capturing mechanisms. Read More

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Pre- and post-synaptic roles of action potential activity in synapse elimination revealed by using ectopic neuromuscular junction formation by a foreign nerve.

Neurosci Lett 2020 03 10;722:134835. Epub 2020 Feb 10.

Department of Neurosciences Biomedicine and Movement Sciences, University of Verona, Strada Le Grazie 8, 37134, Verona, Italy; National Institute of Neuroscience, Verona, Italy. Electronic address:

The formation of the neuromuscular junction (nmj) is based on molecular cascades initiated by neural agrin as well as electrical activity in the neuromuscular structures. This review focuses on the latter factor, emphasizing the multiplicity of its mechanisms in the process of synapse elimination following initial polyneuronal innervation. Pre- and post-synaptic components of activity have in fact been identified through experiments on an adult model of nmj formation: ectopic reinnervation of the rat soleus muscle by the fibular nerve. Read More

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Regeneration of Denervated Skeletal Muscles - Brunelli's CNS-PNS Paradigm.

J Med Life 2019 Oct-Dec;12(4):342-353

Department of Neurology, University Medical Center Schleswig-Holstein, Lübeck, Germany.

The restoration of voluntary muscle activity in posttraumatic paraplegia in both animal experiments and other clinical applications requires reproducibility of a technically-demanding microsurgical procedure, limited by physicians' understanding of Brunelli's spinal cord grafting paradigm. The insufficient clinical investigation of the long-term benefits of the CNS-PNS graft application warrants additional inquiry. The objective of this study is to explore the potential benefits of the first replicated, graft-induced neuroregeneration of denervated skeletal muscle regarding long-term clinical outcomes and to investigate the effect of Cerebrolysin on neuromodulation. Read More

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Unraveling the Role of Receptor for Advanced Glycation End Products (RAGE) and Its Ligands in Myasthenia Gravis.

ACS Chem Neurosci 2020 03 13;11(5):663-673. Epub 2020 Feb 13.

Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece.

Myasthenia gravis (MG) is an autoimmune T cell-dependent B cell-mediated disorder of the neuromuscular junction (NMJ) characterized by fluctuating skeletal muscle weakness, most commonly attributed to pathogenic autoantibodies against postsynaptic nicotinic acetylcholine receptors (AChRs). Although MG pathogenesis is well-documented, there are no objective biomarkers that could effectively correlate with disease severity or MG clinical subtypes, and current treatment approaches are often ineffective. The receptor for advanced glycation end products (RAGE) is a multiligand cell-bound receptor highly implicated in proinflammatory responses and autoimmunity. Read More

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Compensatory neuromuscular junction adaptations of forelimb muscles in focal cortical ischemia in rats.

Brain Behav 2020 03 31;10(3):e01472. Epub 2020 Jan 31.

Physiotherapy Deparment - (DFisio), Laboratorio de Pesquisa em Fisioterapia Neurológica - LaFiN, Federal University of São Carlos, São Carlos, Brazil.

Introduction: Upper limb movements are affected frequently by brain ischemia (BI). Mechanisms involved in recovery and compensatory movements have developed several studies. However, less attention is given to skeletal muscles, where neuromuscular junction (NMJ) has an important role on muscle tropism and functional performance. Read More

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Modification of Neuromuscular Junction Protein Expression by Exercise and Doxorubicin.

Med Sci Sports Exerc 2020 07;52(7):1477-1484

Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL.

Purpose: Doxorubicin (DOX) is a highly effective antitumor agent widely used in cancer treatment. However, it is well established that DOX induces muscular atrophy and impairs force production. Although no therapeutic interventions exist to combat DOX-induced muscle weakness, endurance exercise training has been shown to reduce skeletal muscle damage caused by DOX administration. Read More

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Efficient gene transfer into primary muscle cells to analyze nerve-independent postsynaptic organization in vitro.

Neuromuscul Disord 2019 07 22;29(7):533-542. Epub 2019 May 22.

Faculty of Biological Sciences, Neuromuscular Studies Laboratory (NeSt Lab), Department of Cell Biology, Center for Advanced Microscopy (CMA BioBio), Universidad de Concepción, Casilla 160-C, 4089100 Concepción, Chile. Electronic address:

Acetylcholine receptor (AChR) clustering on the surface of muscle cells is a hallmark of postsynaptic differentiation at the vertebrate neuromuscular junction (NMJ). Even though the assembly of complex postsynaptic apparatuses is known to rely on both, pre- and postsynaptic signals, the identity of muscle-derived proteins modulating postsynaptic assembly and maintenance is still to be fully elucidated. Efficient gene transfer into muscle cells represents a powerful tool to analyze the contribution of muscle proteins on postsynaptic assembly and maintenance. Read More

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Investigational RNAi Therapeutic Targeting C5 Is Efficacious in Pre-clinical Models of Myasthenia Gravis.

Mol Ther Methods Clin Dev 2019 Jun 10;13:484-492. Epub 2019 May 10.

Alnylam Pharmaceuticals, Cambridge, MA 02142, USA.

Complement-mediated damage to the neuromuscular junction (NMJ) is a key mechanism of pathology in myasthenia gravis (MG) and therapeutics inhibiting complement have shown evidence of efficacy in the treatment of MG. In this study, we describe the development of a subcutaneously administered N-acetylgalactosamine (GalNAc)-conjugated small interfering RNA (siRNA) targeting the C5 component of complement that silences C5 expression in the liver (ALN-CC5). Treatment of wild-type rodents with ALN-CC5 resulted in robust and durable suppression of liver C5 expression. Read More

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A hydrogel engineered to deliver minocycline locally to the injured cervical spinal cord protects respiratory neural circuitry and preserves diaphragm function.

Neurobiol Dis 2019 07 25;127:591-604. Epub 2019 Apr 25.

School of Biomedical Engineering, Science and Health Systems, Drexel University, 3141 Chestnut Street, Bossone 7-716, Philadelphia, PA 19104, United States of America. Electronic address:

We tested a biomaterial-based approach to preserve the critical phrenic motor circuitry that controls diaphragm function by locally delivering minocycline hydrochloride (MH) following cervical spinal cord injury (SCI). MH is a clinically-available antibiotic and anti-inflammatory drug that targets a broad range of secondary injury mechanisms via its anti-inflammatory, anti-oxidant and anti-apoptotic properties. However, MH is only neuroprotective at high concentrations that cannot be achieved by systemic administration, which limits its clinical efficacy. Read More

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Knee osteoarthritis induces atrophy and neuromuscular junction remodeling in the quadriceps and tibialis anterior muscles of rats.

Sci Rep 2019 04 24;9(1):6366. Epub 2019 Apr 24.

Physical Therapy Department, Federal University of São Carlos, São Carlos, SP, Brazil.

Knee osteoarthritis (KOA) is associated with muscle weakness, but it is unclear which structures are involved in the muscle changes. This study assessed morphological alterations and the expression of genes and proteins linked to muscular atrophy and neuromuscular junctions (NMJs) in KOA, induced by anterior cruciate ligament transection (ACLT) in rats. Two groups of rats were assessed: control (without intervention) and KOA (ACLT surgery in the right knee). Read More

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Effect of surgically guided axonal regrowth into a 3-way-conduit (isogeneic trifurcated aorta) on functional recovery after facial-nerve reconstruction: Experimental study in rats.

Restor Neurol Neurosci 2019 ;37(2):181-196

Department of Anatomy, Akdeniz University Faculty of Medicine, Antalya, Turkey.

Background: The "post-paralytic syndrome" after facial nerve reconstruction has been attributed to (i) malfunctioning axonal guidance at the fascicular (branches) level, (ii) collateral branching of the transected axons at the lesion site, and (iii) intensive intramuscular terminal sprouting of regenerating axons which causes poly-innervation of the neuromuscular junctions (NMJ).

Objective: The first two reasons were approached by an innovative technique which should provide the re-growing axons optimal conditions to elongate and selectively re-innervate their original muscle groups.

Methods: The transected facial nerve trunk was inserted into a 3-way-conduit (from isogeneic rat abdominal aorta) which should "guide" the re-growing facial axons to the three main branches of the facial nerve (zygomatic, buccal and marginal mandibular). Read More

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Laryngeal Neuromuscular Response to Short- and Long-Term Vocalization Training in Young Male Rats.

J Speech Lang Hear Res 2019 02;62(2):247-256

Department of Communicative Sciences and Disorders, New York University, New York.

Purpose Although vocal training is often purported to restore and rebalance laryngeal muscle function, little is known about the direct effects of vocal training on the laryngeal muscles themselves. Consequently, parameters of vocal exercise dose, such as training duration and intensity, have not been well defined. The goal of this study was to use a behavioral animal model to determine the effects of short- and long-term ultrasonic vocalization (USV) training on USV acoustics, thyroarytenoid (TA) muscle neuromuscular junctions (NMJs), and TA muscle fiber size in adult rats. Read More

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February 2019

Experimental Studies on Facial Nerve Regeneration.

Anat Rec (Hoboken) 2019 08 17;302(8):1287-1303. Epub 2019 Apr 17.

Department of Anatomy 1, University of Cologne, Cologne, Germany.

Insufficient recovery after injury of a peripheral motor nerve is due to (1) inappropriate pathfinding as a result of axonal regrowth to inappropriate targets, (2) excessive collateral axonal branching at the lesion site, and (3) polyinnervation of the neuromuscular junctions (NMJs). The rat facial nerve model is often used because of its simple and reliable readout to measure recovery of function (vibrissal whisking). Over the last decades scientists have concentrated their efforts to combat mostly NMJ polyinnervation, because it turned out to be very difficult to reduce collateral axonal branching and impossible to navigate thousands of axons toward the original fascicles. Read More

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Muscle Fiber Type Changes in Lumbrical Muscles at Early Stages of Chronic Nerve Compression.

Curr Med Sci 2019 Feb 13;39(1):59-66. Epub 2019 Mar 13.

Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Chronic nerve compression (CNC) neuropathy is a common disease in the clinic and provokes paraesthesia, or numbness at early stage. The changes in muscle fiber composition and motor nerve terminal morphology in distal muscles were studied in this study. A well-established CNC model was used to assess the changes in the muscles. Read More

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February 2019