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Neuromuscular junction

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https://www.readbyqxmd.com/read/28821658/opposite-synaptic-alterations-at-the-neuromuscular-junction-in-an-als-mouse-model-when-motor-units-matter
#1
Tremblay Elsa, Martineau Éric, Robitaille Richard
Denervation of the neuromuscular junction (NMJ) precedes the loss of motor neurons (MNs) in amyotrophic lateral sclerosis (ALS). ALS is characterized by a motor unit (MU) dependent vulnerability where MNs with fast-fatigable (FF) characteristics are lost first, followed by fast-fatigue resistant (FR) and slow (S) ones. However, changes of NMJ properties as a function of MU types remain debated. We hypothesized that NMJ synaptic functions would be altered precociously in a MU specific manner, prior to structural alterations of the NMJ...
August 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28819043/increased-acetylation-of-microtubules-rescues-human-tau-induced-microtubule-defects-and-neuromuscular-junction-abnormalities-in-drosophila
#2
Chuan-Xi Mao, Xue Wen, Shan Jin, Yong Q Zhang
Tau normally associates with and stabilizes microtubules (MTs), but is hyperphosphorylated and aggregated into neurofibrillary tangles in Alzheimer's disease and related neurodegenerative diseases, which are collectively known as tauopathies. MTs are regulated by different forms of post-translational modification including acetylation; acetylated MTs represent a more stable microtubule population. In our previous study, we show that inhibition of histone deacetylase 6 (HDAC6), which deacetylates tubulin at lysine 40, rescues defects in MTs and in neuromuscular junction growth caused by tau overexpression...
August 17, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28811140/divergent-effects-of-resistance-training-and-anabolic-steroid-on-the-postsynaptic-region-of-different-skeletal-muscles-of-aged-rats
#3
Walter Krause Neto, Wellington de Assis Silva, Adriano Polican Ciena, Carlos Alberto Anaruma, Eliane Florencio Gama
This study aimed to analyze the effects of resistance training associated with testosterone administration in the neuromuscular junction (NMJ) postsynaptic region of different skeletal muscle types of aged rats. Wistar rats were divided into: SEI - 20-months-old control, SEF - 24-months-old control, T - 20-months-old with testosterone, S - 20-months-old resistance trained and ST - 20-months-old with resistance training associated with testosterone propionate. All groups were submitted to familiarization and maximum load carrying testing (MLCT)...
August 12, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28810241/molecular-epidemiology-of-charcot-marie-tooth-disease-in-northern-ostrobothnia-finland-a-population-based-study
#4
Maria Marttila, Laura Kytövuori, Seppo Helisalmi, Mika Kallio, Marjo Laitinen, Mikko Hiltunen, Mikko Kärppä, Kari Majamaa
BACKGROUND: Charcot-Marie-Tooth (CMT) disease is the most common hereditary neuromuscular disorder with a population prevalence of 9.7-82.3/100,000. In this study, we have estimated the prevalence of CMT and its subtypes in Finland and examined the frequency of molecular etiologies. METHODS: A population-based survey included adult patients with peripheral neuropathy from the province of Northern Ostrobothnia, Finland. Secondary causes of peripheral polyneuropathy were excluded and patients with clinical and neurophysiological features pertinent with CMT were included...
August 16, 2017: Neuroepidemiology
https://www.readbyqxmd.com/read/28809841/measuring-neuromuscular-junction-functionality
#5
Emanuele Rizzuto, Simona Pisu, Carmine Nicoletti, Zaccaria Del Prete, Antonio Musarò
Neuromuscular junction (NMJ) functionality plays a pivotal role when studying diseases in which the communication between motor neuron and muscle is impaired, such as aging and amyotrophic lateral sclerosis (ALS). Here we describe an experimental protocol that can be used to measure NMJ functionality by combining two types of electrical stimulation: direct muscle membrane stimulation and the stimulation through the nerve. The comparison of the muscle response to these two different stimulations can help to define, at the functional level, potential alterations in the NMJ that lead to functional decline in muscle...
August 6, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28803817/6mwt-can-identify-type-3-sma-patients-with-neuromuscular-junction-dysfunction
#6
REVIEW
Maria Carmela Pera, Marco Luigetti, Marika Pane, Giorgia Coratti, Nicola Forcina, Lavinia Fanelli, Elena S Mazzone, Laura Antonaci, Leonardo Lapenta, Concetta Palermo, Domiziana Ranalli, Giuseppe Granata, Mauro Lomonaco, Serenella Servidei, Eugenio Mercuri
The aim of the study was to establish if the decrease in gait velocity on the 6 minute walk test relates to signs of neuromuscular junction dysfunction in spinal muscular atrophy type 3 patients. 6 minute walk test and low-rate repetitive nerve stimulation test were performed in fifteen ambulant patients with spinal muscular atrophy type 3 of age between 9 and 66 years. The 6 minute walk distance ranged between 66 and 575 m. The difference between the first and the 6th minute ranged between 0 and -69%. The low-rate repetitive nerve stimulation test measured in % of loss ranged between -31...
July 14, 2017: Neuromuscular Disorders: NMD
https://www.readbyqxmd.com/read/28800600/botulinum-neurotoxin-c-mutants-reveal-different-effects-of-syntaxin-or-snap-25-proteolysis-on-neuromuscular-transmission
#7
Giulia Zanetti, Stefan Sikorra, Andreas Rummel, Nadja Krez, Elisa Duregotti, Samuele Negro, Tina Henke, Ornella Rossetto, Thomas Binz, Marco Pirazzini
Botulinum neurotoxin serotype C (BoNT/C) is a neuroparalytic toxin associated with outbreaks of animal botulism, particularly in birds, and is the only BoNT known to cleave two different SNARE proteins, SNAP-25 and syntaxin. BoNT/C was shown to be a good substitute for BoNT/A1 in human dystonia therapy because of its long lasting effects and absence of neuromuscular damage. Two triple mutants of BoNT/C, namely BoNT/C S51T/R52N/N53P (BoNT/C α-51) and BoNT/C L200W/M221W/I226W (BoNT/C α-3W), were recently reported to selectively cleave syntaxin and have been used here to evaluate the individual contribution of SNAP-25 and syntaxin cleavage to the effect of BoNT/C in vivo...
August 11, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28798955/super-resolution-microscopy-reveals-a-nanoscale-organization-of-acetylcholine-receptors-for-trans-synaptic-alignment-at-neuromuscular-synapses
#8
Amanda L York, James Q Zheng
The neuromuscular junction (NMJ) is a chemical synapse formed between motoneurons and skeletal muscle fibers. The vertebrate NMJ uses acetylcholine (ACh) as the neurotransmitter and features numerous invaginations of the postsynaptic muscle membrane termed junctional folds. ACh receptors (AChRs) are believed to be concentrated on the crest of junctional folds but their spatial organization remains to be fully understood. In this study, we utilized super-resolution microscopy to examine the nanoscale organization of AChRs at NMJ...
July 2017: ENeuro
https://www.readbyqxmd.com/read/28798922/practical-approach-to-the-patient-with-acute-neuromuscular-weakness
#9
REVIEW
Rajeev Nayak
Acute neuromuscular paralysis (ANMP) is a clinical syndrome characterized by rapid onset muscle weakness progressing to maximum severity within several days to weeks (less than 4 wk). Bulbar and respiratory muscle weakness may or may not be present. It is a common neurological emergency which requires immediate and careful investigations to determine the etiology because accurate diagnosis has significant impact on therapy and prognosis. Respiratory failure caused by neuromuscular weakness is considered as more critical than lung disease because its development may be insidious or subtle until sudden decompensation leads to life threatening hypoxia...
July 16, 2017: World Journal of Clinical Cases
https://www.readbyqxmd.com/read/28791707/preface-cholinergic-mechanisms
#10
Marco A M Prado, Pascale Marchot, Israel Silman
This special issue is a companion to the meeting 'XVth International Symposium on Cholinergic Mechanisms', and is edited by Israel Silman, Marco Prado and Pascale Marchot. In the review articles, renowned researchers in the field capture key mechanisms of cholinergic neurotransmission, from genomic amplification of cholinesterase genes, splicing and post-translational modifications; features of the neuromuscular junction, implications of cholinergic circuitry that are relevant to addiction, anxiety and mood, to preclinical models, protein biomarkers, and clinical findings that are relevant to pathology, for example, developmental neurotoxicity...
August 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28790398/shedding-light-on-alzheimer-s-%C3%AE-amyloidosis-photosensitized-methylene-blue-inhibits-self-assembly-of-%C3%AE-amyloid-peptides-and-disintegrates-their-aggregates
#11
Byung Il Lee, Yoon Seok Suh, You Jung Chung, Kweon Yu, Chan Beum Park
Abnormal aggregation of β-amyloid (Aβ) peptides is a major hallmark of Alzheimer's disease (AD). In spite of numerous attempts to prevent the β-amyloidosis, no effective drugs for treating AD have been developed to date. Among many candidate chemicals, methylene blue (MB) has proved its therapeutic potential for AD in a number of in vitro and in vivo studies; but the result of recent clinical trials performed with MB and its derivative was negative. Here, with the aid of multiple photochemical analyses, we first report that photoexcited MB molecules can block Aβ42 aggregation in vitro...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28780847/-characteristics-of-repetitive-nerve-stimulation-in-53-cases-of-amyotrophic-lateral-sclerosis
#12
W X Liu, Z H Chen, L Ling, Y T Ren, B Sun, F Yang, F Cui, X S Huang
Objective: To investigate the feature of repetitive nerve stimulation (RNS) in patients with amyotrophic lateral sclerosis (ALS) and correlation between RNS and clinical features and electromyography (EMG) findings of the corresponding muscle. Methods: Needle EMG and RNS were performed in 53 patients with ALS, who were recruited into Department of Neurology of Chinese PLA general hospital during April to December in 2016. Decrement of the compond muscle action potential (CMAP) in response to RNS of different nerves and stimulus frequencies was compared...
August 1, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28780294/pathophysiology-and-immunological-profile-of-myasthenia-gravis-and-its-subgroups
#13
REVIEW
Fredrik Romi, Yu Hong, Nils Erik Gilhus
Myasthenia gravis (MG) is an autoimmune antibody-mediated disease characterized by muscle weakness and fatigability. It is believed that the initial steps triggering humoral immunity in MG take place inside thymic tissue and thymoma. The immune response against one or several epitopes expressed on thymic tissue cells spills over to neuromuscular junction components sharing the same epitope causing humoral autoimmunity and antibody production. The main cause of MG is acetylcholine receptor antibodies. However, many other neuromuscular junction membrane protein targets, intracellular and extracellular proteins are suggested to participate in MG pathophysiology...
August 3, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28777299/ultrafast-and-slow-cholinergic-transmission-different-involvement-of-acetylcholinesterase-molecular-forms
#14
REVIEW
Yves Dunant, Victor Gisiger
Acetylcholine (ACh), an ubiquitous mediator substance broadly expressed in nature, acts as neurotransmitter in cholinergic synapses, generating specific communications with different time-courses. (1) Ultrafast transmission. Vertebrate neuromuscular junctions (NMJs) and nerve-electroplaque junctions (NEJs) are the fastest cholinergic synapses; able to transmit brief impulses (1-4 ms) at high frequencies. The collagen-tailed A12 acetylcholinesterase is concentrated in the synaptic cleft of NMJs and NEJs, were it curtails the postsynaptic response by ultrafast ACh hydrolysis...
August 4, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28770114/human-app-gene-expression-alters-active-zone-distribution-and-spontaneous-neurotransmitter-release-at-the-drosophila-larval-neuromuscular-junction
#15
Ekaterina A Saburova, Alexander N Vasiliev, Violetta V Kravtsova, Elena V Ryabova, Andrey L Zefirov, Olga I Bolshakova, Svetlana V Sarantseva, Igor I Krivoi
This study provides further insight into the molecular mechanisms that control neurotransmitter release. Experiments were performed on larval neuromuscular junctions of transgenic Drosophila melanogaster lines with different levels of human amyloid precursor protein (APP) production. To express human genes in motor neurons of Drosophila, the UAS-GAL4 system was used. Human APP gene expression increased the number of synaptic boutons per neuromuscular junction. The total number of active zones, detected by Bruchpilot protein puncta distribution, remained unchanged; however, the average number of active zones per bouton decreased...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/28765879/mass-spectrometric-identification-of-dystrophin-the-protein-product-of-the-duchenne-muscular-dystrophy%C3%A2-gene-in-distinct-muscle-surface-membranes
#16
Sandra Murphy, Kay Ohlendieck
Supramolecular membrane complexes of low abundance are difficult to study by routine bioanalytical techniques. The plasmalemmal complex consisting of sarcoglycans, dystroglycans, dystrobrevins and syntrophins, which is closely associated with the membrane cytoskeletal protein dystrophin, represents such a high‑molecular‑mass protein assembly in skeletal muscles. The almost complete loss of the dystrophin isoform Dp427‑M and concomitant reduction in the dystrophin‑associated glycoprotein complex is the underlying cause of the highly progressive neuromuscular disorder named Duchenne muscular dystrophy...
July 27, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28762314/insights-into-nicotinic-receptor-signaling-in-nicotine-addiction-implications-for-prevention-and-treatment
#17
Wuyi Liu, Ming D Li
Nicotinic acetylcholine receptors (nAChRs) belong to the Cys-loop ligand-gated ion-channel (LGIC) superfamily, which also includes the GABA, glycine, and serotonin receptors. Many nAChR subunits have been identified and shown to be involved in signal transduction on binding to them of either the neurotransmitter acetylcholine or exogenous ligands such as nicotine. The nAChRs are pentameric assemblies of homologous subunits surrounding a central pore that gates cation flux, and they are expressed at neuromuscular junctions throughout the nervous system...
August 1, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28759703/extracorporeal-shock-wave-treatment-can-selectively-destroy-endplates-in-neuromuscular-junctions
#18
Tomonori Kenmoku, Noriko Nemoto, Nahoko Iwakura, Nobuyasu Ochiai, Kentaro Uchida, Takashi Saisu, Seiji Ohtori, Koichi Nakagawa, Takahisa Sasho, Masashi Takaso
INTRODUCTION: This study assessed the effect of radial extracorporeal shock wave (rESW) exposure on neuromuscular transmission and neuromuscular junction (NMJ) morphology. METHODS: We applied 2,000 rESWs at 0.18 mJ/mm(2) and a frequency of 15 Hz to the right calf of male rats, measured the compound muscle action potential (CMAP) and examined NMJ morphology using electron microscopy. Left calf muscles were used as controls. RESULTS: rESW exposure significantly reduced CMAP amplitude without delayed latency in exposed muscles compared to controls...
July 31, 2017: Muscle & Nerve
https://www.readbyqxmd.com/read/28759131/neuromuscular-adaptability-of-male-and-female-rats-to-muscle-unloading
#19
Michael R Deschenes, Matthew A Adan, Maria C Kapral, Kaitlin A Kressin, Colleen M Leathrum, Anna Seo, Shuhan Li, Ellen C Schaffrey
Previously, it has been shown that following muscle unloading, males and females experience different maladaptations in neuromuscular function. As a follow-up, the present investigation sought to determine if male and female neuromuscular systems demonstrated similar, or disparate morphological adaptations to muscle unloading. Twenty young adult male, and 20 young adult female rats were randomly assigned to one of two treatment protocols: muscle unloading, or control conditions. Following the 2-week intervention period, immunofluorescent procedures were used to quantify pre- and post-synaptic features of neuromuscular junctions (NMJs), and to assess myofiber profiles (size and fiber type composition) of the soleus, plantaris, and EDL muscles...
July 31, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28755059/nusinersen-the-first-option-beyond-supportive-care-for-spinal-muscular-atrophy
#20
REVIEW
Vikas Maharshi, Shazia Hasan
Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by degeneration of spinal motor neurons and poses significant adverse outcome in affected population. Survival motor neuron 1 (SMN1) protein encoded by SMN1 gene located on 5q(13) is critical for survival and functioning of motor neurons. Almost identical gene SMN2, present on the same chromosome, produces a small truncated protein (SMN2) because of skipping of exon 7 from translation due to translation silent C6U substitution in exon 7 of SMN2 pre-mRNA transcript...
July 28, 2017: Clinical Drug Investigation
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