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Neuromuscular junction

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https://www.readbyqxmd.com/read/28544556/electrophysiological-analysis-of-synaptic-transmission-in-drosophila
#1
REVIEW
Maria Bykhovskaia, Alexander Vasin
Synaptic transmission is dynamic, plastic, and highly regulated. Drosophila is an advantageous model system for genetic and molecular studies of presynaptic and postsynaptic mechanisms and plasticity. Electrical recordings of synaptic responses represent a wide-spread approach to study neuronal signaling and synaptic transmission. We discuss experimental techniques that allow monitoring synaptic transmission in Drosophila neuromuscular and central systems. Recordings of synaptic potentials or currents at the larval neuromuscular junction (NMJ) are most common and provide numerous technical advantages due to robustness of the preparation, large and identifiable muscles, and synaptic boutons which can be readily visualized...
May 24, 2017: Wiley Interdisciplinary Reviews. Developmental Biology
https://www.readbyqxmd.com/read/28543723/neuromuscular-junctions-nmjs-ultrastructural-analysis-and-nicotinic-acetylcholine-receptor-nachr-subunit-mrna-expression-in-offspring-subjected-to-protein-restriction-throughout-pregnancy
#2
Paula Aiello Tomé de Souza Castro, Ludimila Canuto Faccioni, Patrícia Aline Boer, Robson Francisco Carvalho, Selma Maria Michelin Matheus, Maeli Dal-Pai-Silva
Protein restriction during gestation can alter the skeletal muscle phenotype of offspring; however, little is known with regard to whether this also affects the neuromuscular junction (NMJ), as muscle phenotype maintenance depends upon NMJ functional integrity. This study aimed to evaluate the effects of a low protein (6%) intake by dams throughout gestation on male offspring NMJ morphology and nicotinic acetylcholine receptor (nAChR) α1, γ and ε subunit expression in the soleus (SOL) and extensor digitorum longus (EDL) muscles...
May 25, 2017: International Journal of Experimental Pathology
https://www.readbyqxmd.com/read/28538252/concurrent-paraspinous-myopathy-and-myasthenia-gravis
#3
Alissa E Romano, Zaid Al-Qudah, Henry J Kaminski, Bashar Katirji, Karim Salame
Paraspinous myopathy is a rare neuromuscular disorder characterized by selective involvement of the cervical, thoracic, or lumbar muscles. Leading clinical features include a bent spine or dropped head (antecollis). In myasthenia gravis (MG), patients may have camptocormia secondary to neuromuscular junction dysfunction of the paraspinal muscles, and this condition usually responds to acetylcholinesterase inhibitors or immunosuppressive treatments. However, concomitant MG and paraspinous myopathy with histologic and electrophysiologic evidence of myopathic changes of the paraspinal muscles has only been reported twice in the literature...
June 2017: Journal of Clinical Neuromuscular Disease
https://www.readbyqxmd.com/read/28534855/rbc-adherence-of-immune-complexes-containing-botulinum-toxin-improves-neutralization-and-macrophage-uptake
#4
Fetweh H Al-Saleem, Rashmi Sharma, Rama Devudu Puligedda, Md Elias, Chandana Devi Kattala, Paul M Simon, Lance L Simpson, Scott K Dessain
In the paralytic disease botulism, the botulinum neurotoxin (BoNT) passes through the bloodstream to reach and inactivate neuromuscular junctions. Monoclonal antibodies (mAbs) may be useful BoNT countermeasures, as mAb combinations can rapidly clear BoNT from the blood circulation. We have previously shown that the BoNT-neutralizing potency of mAbs can be improved through red blood cell (RBC) immunoadherence. For example, a fusion protein (FP) that adheres biotinylated mAbs to the RBC surface enabled a pair of mAbs to neutralize 5000 LD50 BoNT/A in the mouse protection assay...
May 19, 2017: Toxins
https://www.readbyqxmd.com/read/28533206/myostatin-like-proteins-regulate-synaptic-function-and-neuronal-morphology
#5
Hrvoje Augustin, Kieran McGourty, Joern R Steinert, Helena M Cochemé, Jennifer Adcott, Melissa Cabecinha, Alec Vincent, Els F Halff, Josef T Kittler, Emmanuel Boucrot, Linda Partridge
Growth factors of the TGF-β superfamily play key roles in regulating neuronal and muscle function. Myostatin (or GDF8) and GDF11 are potent negative regulators of skeletal muscle mass. However, expression of both Myostatin and its cognate receptors in other tissues, including brain and peripheral nerves, suggests a potential wider biological role. Here, we show that Myoglianin (MYO), the Drosophila homolog of Myostatin and GDF11, regulates not only body weight and muscle size, but also inhibits neuromuscular synapse strength and composition in a Smad2-dependent manner...
May 22, 2017: Development
https://www.readbyqxmd.com/read/28522038/injectable-and-topical-neurotoxins-in-dermatology-basic-science-anatomy-and-therapeutic-agents
#6
REVIEW
Cerrene N Giordano, Seth L Matarasso, David M Ozog
Botulinum toxin is a potentially deadly anaerobic bacterial toxin that acts by inhibiting release of acetylcholine at the neuromuscular junction, thereby inhibiting contraction of the exposed striated muscle. There are currently 4 botulinum toxin preparations approved by the US Food and Drug Administration (FDA): onabotulinumtoxin, abobotulinumtoxin, incobotulinumtoxin and rimabotulinumtoxin. While significant overlap exists, each product has unique properties and specifications, including dosing, diffusion, and storage...
June 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/28520784/presynaptic-a%C3%AE-40-prevents-synapse-addition-in-the-adult-drosophila-neuromuscular-junction
#7
Begoña López-Arias, Enrique Turiégano, Ignacio Monedero, Inmaculada Canal, Laura Torroja
Complexity in the processing of the Amyloid Precursor Protein, which generates a mixture of βamyloid peptides, lies beneath the difficulty in understanding the etiology of Alzheimer's disease. Moreover, whether Aβ peptides have any physiological role in neurons is an unresolved question. By expressing single, defined Aβ peptides in Drosophila, specific effects can be discriminated in vivo. Here, we show that in the adult neuromuscular junction (NMJ), presynaptic expression of Aβ40 hinders the synaptic addition that normally occurs in adults, yielding NMJs with an invariable number of active zones at all ages tested...
2017: PloS One
https://www.readbyqxmd.com/read/28518121/two-algorithms-for-high-throughput-and-multi-parametric-quantification-of-drosophila-neuromuscular-junction-morphology
#8
Anna Castells-Nobau, Bonnie Nijhof, Ilse Eidhof, Louis Wolf, Jolanda M Scheffer-de Gooyert, Ignacio Monedero, Laura Torroja, Jeroen A W M van der Laak, Annette Schenck
Synaptic morphology is tightly related to synaptic efficacy, and in many cases morphological synapse defects ultimately lead to synaptic malfunction. The Drosophila larval neuromuscular junction (NMJ), a well-established model for glutamatergic synapses, has been extensively studied for decades. Identification of mutations causing NMJ morphological defects revealed a repertoire of genes that regulate synapse development and function. Many of these were identified in large-scale studies that focused on qualitative approaches to detect morphological abnormalities of the Drosophila NMJ...
May 3, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28515212/regulation-of-wnt-signaling-at-the-neuromuscular-junction-by-the-immunoglobulin-super-family-protein-rig-3-in-caenorhabditis-elegans
#9
Pratima Pandey, Ashwani Bhardwaj, Kavita Babu
Perturbations in synaptic function could affect the normal behavior of an animal, making it important to understand the regulatory mechanisms of synaptic signaling. Previous work has shown that in Caenorhabditis elegans an immunoglobulin super-family protein, RIG-3, functions in pre-synaptic neurons to maintain normal acetylcholine receptor levels at the neuromuscular junction (NMJ). In this study we elucidate the molecular and functional mechanism of RIG-3. We demonstrate by genetic and BiFC (Bi-molecular Fluorescence Complementation) assays that pre-synaptic RIG-3 functions by directly interacting with the immunoglobulin domain of the non-conventional Wnt receptor, ROR receptor tyrosine kinase (RTK), CAM-1, that functions in post-synaptic body-wall muscles...
May 17, 2017: Genetics
https://www.readbyqxmd.com/read/28503133/behavioral-senescence-and-aging-related-changes-in-motor-neurons-and-brain-neuromodulator-levels-are-ameliorated-by-lifespan-extending-reproductive-dormancy-in-drosophila
#10
Sifang Liao, Susan Broughton, Dick R Nässel
The lifespan of Drosophilamelanogaster can be extended substantially by inducing reproductive dormancy (also known as diapause) by lowered temperature and short days. This increase of longevity is accompanied by lowered metabolism and increased stress tolerance. We ask here whether behavioral senescence is ameliorated during adult dormancy. To study this we kept flies for seven or more weeks in normal rearing conditions or in diapause conditions and compared to 1-week-old flies in different behavioral assays of sleep, negative geotaxis and exploratory walking...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28500055/rnai-mediated-reverse-genetic-screen-identified-drosophila-chaperones-regulating-eye-and-neuromuscular-junction-morphology
#11
Sandeep Raut, Bhagaban Mallik, Arpan Parichha, Amrutha V, Chandan Sahi, Vimlesh Kumar
Accumulation of toxic proteins in neurons have been linked with the onset of neurodegenerative diseases, which in many cases, are characterized by altered neuronal function and synapse loss. Molecular chaperones help protein folding and resolubilization of unfolded proteins thereby reducing the protein aggregation stress. While most of the chaperones are expressed in neurons, their functional relevance largely remains unknown. Here, using bioinformatics analysis, we identified 95 Drosophila chaperones and classified them into seven different classes...
May 12, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28498949/proteolytic-cleavage-is-required-for-functional-neuroligin-2-maturation-and-trafficking-in-drosophila
#12
Renjun Tu, Jinjun Qian, Menglong Rui, Nana Tao, Mingkuan Sun, Yan Zhuang, Huihui Lv, Junhai Han, Moyi Li, Wei Xie
Neuroligins are transmembrane cell adhesion molecules playing essential roles in synapse development and function. Genetic mutations in neuroligin genes have been linked with some neurodevelopmental disorders such as autism. These mutated Neuroligins are mostly retained in the endoplasmic reticulum (ER). However, the mechanisms underlying normal Neuroligin maturation and trafficking have remained largely unknown. Here, we found that Drosophila Neuroligin 2 (DNlg2) undergoes proteolytic cleavage in the ER in a variety of Drosophila tissues throughout developmental stages...
May 11, 2017: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/28495800/mechanically-patterned-neuromuscular-junctions-in-a-dish-have-improved-functional-maturation
#13
Cassandra L Happe, Kevin P Tenerelli, Anastasia K Gromova, Frederic Kolb, Adam J Engler
Motor neuron (MN) diseases are progressive disorders resulting from degeneration of neuromuscular junctions (NMJs), which form the connection between MNs and muscle fibers. NMJ-in-a-dish models have been developed to examine human MN-associated dysfunction with disease; however such co-culture models have randomly oriented myotubes with immature synapses that contract asynchronously. Mechanically patterned (MP) extracellular matrix with alternating soft and stiff stripes improve current NMJ-in-a-dish models by inducing both mouse and human myoblast durotaxis to stripes where they aligned, differentiated, and fused into patterned myotubes...
May 11, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28490756/expressing-acetylcholine-receptors-after-innervation-suppresses-spontaneous-vesicle-release-and-causes-muscle-fatigue
#14
Meghan Mott, Victor M Luna, Jee-Young Park, Gerald B Downes, Kimberly Epley, Fumihito Ono
The formation and function of synapses are tightly orchestrated by the precise timing of expression of specific molecules during development. In this study, we determined how manipulating the timing of expression of postsynaptic acetylcholine receptors (AChRs) impacts presynaptic release by establishing a genetically engineered zebrafish line in which we can freely control the timing of AChR expression in an AChR-less fish background. With the delayed induction of AChR expression after an extensive period of AChR-less development, paralyzed fish displayed a remarkable level of recovery, exhibiting a robust escape response following developmental delay...
May 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28490573/dok7-gene-therapy-enhances-motor-activity-and-life-span-in-als-model-mice
#15
Sadanori Miyoshi, Tohru Tezuka, Sumimasa Arimura, Taro Tomono, Takashi Okada, Yuji Yamanashi
Amyotrophic lateral sclerosis (ALS) is a progressive, multifactorial motor neurodegenerative disease with severe muscle atrophy. The glutamate release inhibitor riluzole is the only medication approved by the FDA, and prolongs patient life span by a few months, testifying to a strong need for new treatment strategies. In ALS, motor neuron degeneration first becomes evident at the motor nerve terminals in neuromuscular junctions (NMJs), the cholinergic synapse between motor neuron and skeletal muscle; degeneration then progresses proximally, implicating the NMJ as a therapeutic target...
May 10, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28489965/evidence-for-the-subsynaptic-zone-as-a-preferential-site-for-chrn-recycling-at-neuromuscular-junctions
#16
Franziska Wild, Muzamil Majid Khan, Rüdiger Rudolf
Vertebrate skeletal muscle contraction is mediated by nicotinic acetylcholine receptors (CHRN). Endocytosis and recycling of CHRN regulate their proper abundance at nerve-muscle synapses, i.e. neuromuscular junctions. Recent work showed that RAB5 is essential for CHRN endocytosis. Here, using in vivo-imaging of endocytosed CHRN and RAB-GFP fusion proteins, we deliver evidence for differential effects of RAB5-GFP, RAB4-GFP, and RAB11-GFP on CHRN endocytosis. Furthermore, while newly endocytosed CHRN colocalized with RAB5-GFP over large stretches of muscle fibers, RAB4-GFP and RAB11-GFP colocalized with endocytosed CHRN almost exclusively at neuromuscular junctions...
May 10, 2017: Small GTPases
https://www.readbyqxmd.com/read/28489002/usp5-leon-deubiquitinase-confines-postsynaptic-growth-by-maintaining-ubiquitin-homeostasis-through-ubiquilin
#17
Chien-Hsiang Wang, Yi-Chun Huang, Pei-Yi Chen, Ying-Ju Cheng, Hsiu-Hua Kao, Haiwei Pi, Cheng-Ting Chien
Synapse formation and growth are tightly controlled processes. How synaptic growth is terminated after reaching proper size remains unclear. Here, we show that Leon, the Drosophila USP5 deubiquitinase, controls postsynaptic growth. In leon mutants, postsynaptic specializations of neuromuscular junctions are dramatically expanded, including the subsynaptic reticulum, the postsynaptic density, and the glutamate receptor cluster. Expansion of these postsynaptic features is caused by a disruption of ubiquitin homeostasis with accumulation of free ubiquitin chains and ubiquitinated substrates in the leon mutant...
May 10, 2017: ELife
https://www.readbyqxmd.com/read/28488683/progressive-hereditary-spastic-paraplegia-caused-by-a-homozygous-ky-mutation
#18
Yuval Yogev, Yonatan Perez, Iris Noyman, Anwar Abu Madegem, Hagit Flusser, Zamir Shorer, Eugene Cohen, Leonid Kachko, Analia Michaelovsky, Ruth Birk, Arie Koifman, Max Drabkin, Ohad Wormser, Daniel Halperin, Rotem Kadir, Ohad S Birk
Twelve individuals of consanguineous Bedouin kindred presented with autosomal recessive progressive spastic paraplegia evident as of age 0-24 months, with spasticity of lower limbs, hyperreflexia, toe walking and equinus deformity. Kyphoscolisois was evident in older patients. Most had atrophy of the lateral aspects of the tongue and few had intellectual disability. Nerve conduction velocity, electromyography and head and spinal cord magnetic resonance imaging were normal in tested subjects. Muscle biopsy showed occasional central nuclei and fiber size variability with small angular fibers...
May 10, 2017: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/28488382/neuron-specific-knockdown-of-the-drosophila-fat-induces-reduction-of-life-span-deficient-locomotive-ability-shortening-of-motoneuron-terminal-branches-and-defects-in-axonal-targeting
#19
Aya Nakamura, Ryo Tanaka, Kazushige Morishita, Hideki Yoshida, Yujiro Higuchi, Hiroshi Takashima, Masamitsu Yamaguchi
Mutations in FAT4 gene, one of the human FAT family genes, have been identified in Van Maldergem syndrome (VMS) and Hennekam lymphangiectasia-lymphedema syndrome (HS). The FAT4 gene encodes a large protein with extracellular cadherin repeats, EGF-like domains and Laminin G-like domains. FAT4 plays a role in tumor suppression and planar cell polarity. Drosophila contains a human FAT4 homologue, fat. Drosophila fat has been mainly studied with Drosophila eye and wing systems. Here, we specially knocked down Drosophila fat in nerve system...
May 9, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28480963/use-of-stimulated-electromyography-in-the-analysis-of-the-neuromuscular-junction-in-children
#20
REVIEW
Matthew C Pitt
A screening test is required to diagnose disorders of the neuromuscular junction (NMJ) in children. This Review describes the development of stimulation potential analysis with concentric needle electrodes (SPACE). This nomenclature was chosen to distinguish the technique from single-fiber methodology because of the difficulties in identifying single-fiber potentials in most studies, particularly those with the most severe abnormalities of the NMJ. Performed on orbicularis oculi in children with proven or probable disorders of the NMJ, it demonstrated a sensitivity of 84%, specificity of 71%, negative predictive value of 95%, and positive predictive value of 36%...
May 8, 2017: Muscle & Nerve
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