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neuromuscular junction physiology

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https://www.readbyqxmd.com/read/28072465/splicing-regulation-and-dysregulation-of-cholinergic-genes-expressed-at-the-neuromuscular-junction
#1
REVIEW
Kinji Ohno, Mohammad Alinoor Rahman, Mohammad Nazim, Farhana Nasrin, Yingni Lin, Jun-Ichi Takeda, Akio Masuda
We humans have evolved by acquiring diversity of alternative RNA metabolisms including alternative means of splicing and transcribing non-coding genes, and not by acquiring new coding genes. Tissue-specific and developmental stage-specific alternative RNA splicing is achieved by tightly regulated spatiotemporal regulation of expressions and activations of RNA-binding proteins that recognize their cognate splicing cis-elements on nascent RNA transcripts. Genes expressed at the neuromuscular junction (NMJ) are also alternatively spliced...
January 10, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27998908/loss-of-laminin-%C3%AE-4-results-in-pre-and-postsynaptic-modifications-at-the-neuromuscular-junction
#2
Kirat K Chand, Kah Meng Lee, Nickolas A Lavidis, Peter G Noakes
Synaptic basal lamina such as laminin-421 (α4β2γ1) mediate differentiation of the neuromuscular junction (NMJ). Laminins interact with their pre- or postsynaptic receptors to provide stability and alignment of the pre- to postsynaptic specializations. Knockout of the lama4 gene does not alter gross NMJ morphogenesis. However, mice deficient in laminin-α4 (lama4(-/-)) display disruptions in the alignment of the active zones and postsynaptic folds at the NMJ, although the physiological consequences of this loss have not been examined...
December 20, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27990107/a-novel-striated-muscle-specific-myosin-blocking-drug-for-the-study-of-neuromuscular-physiology
#3
Dante J Heredia, Douglas Schubert, Siddhardha Maligireddy, Grant W Hennig, Thomas W Gould
The failure to transmit neural action potentials (APs) into muscle APs is referred to as neuromuscular transmission failure (NTF). Although synaptic dysfunction occurs in a variety of neuromuscular diseases and impaired neurotransmission contributes to muscle fatigue, direct evaluation of neurotransmission by measurement of successfully transduced muscle APs is difficult due to the subsequent movements produced by muscle. Moreover, the voltage-gated sodium channel inhibitor used to study neurotransmitter release at the adult neuromuscular junction is ineffective in embryonic tissue, making it nearly impossible to precisely measure any aspect of neurotransmission in embryonic lethal mouse mutants...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27927794/nmj-morph-reveals-principal-components-of-synaptic-morphology-influencing-structure-function-relationships-at-the-neuromuscular-junction
#4
Ross A Jones, Caitlan D Reich, Kosala N Dissanayake, Fanney Kristmundsdottir, Gordon S Findlater, Richard R Ribchester, Martin W Simmen, Thomas H Gillingwater
The ability to form synapses is one of the fundamental properties required by the mammalian nervous system to generate network connectivity. Structural and functional diversity among synaptic populations is a key hallmark of network diversity, and yet we know comparatively little about the morphological principles that govern variability in the size, shape and strength of synapses. Using the mouse neuromuscular junction (NMJ) as an experimentally accessible model synapse, we report on the development of a robust, standardized methodology to facilitate comparative morphometric analysis of synapses ('NMJ-morph')...
December 2016: Open Biology
https://www.readbyqxmd.com/read/27810937/deficiency-of-cpeb2-confined-choline-acetyltransferase-expression-in-the-dorsal-motor-nucleus-of-vagus-causes-hyperactivated-parasympathetic-signaling-associated-bronchoconstriction
#5
Yen-Ting Lai, Chun-Kuei Su, Si-Tse Jiang, Ya-Jen Chang, Alan Chuan-Ying Lai, Yi-Shuian Huang
: Cytoplasmic polyadenylation element binding protein 2 (CPEB2) is an RNA-binding protein and translational regulator. To understand the physiological function of CPEB2, we generated CPEB2 knock-out (KO) mice and found that most died within 3 d after birth. CPEB2 is highly expressed in the brainstem, which controls vital functions, such as breathing. Whole-body plethysmography revealed that KO neonates had aberrant respiration with frequent apnea. Nevertheless, the morphology and function of the respiratory rhythm generator and diaphragm neuromuscular junctions appeared normal...
December 14, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27773584/branch-specific-microtubule-destabilization-mediates-axon-branch-loss-during-neuromuscular-synapse-elimination
#6
Monika S Brill, Tatjana Kleele, Laura Ruschkies, Mengzhe Wang, Natalia A Marahori, Miriam S Reuter, Torben J Hausrat, Emily Weigand, Matthew Fisher, Andrea Ahles, Stefan Engelhardt, Derron L Bishop, Matthias Kneussel, Thomas Misgeld
Developmental axon remodeling is characterized by the selective removal of branches from axon arbors. The mechanisms that underlie such branch loss are largely unknown. Additionally, how neuronal resources are specifically assigned to the branches of remodeling arbors is not understood. Here we show that axon branch loss at the developing mouse neuromuscular junction is mediated by branch-specific microtubule severing, which results in local disassembly of the microtubule cytoskeleton and loss of axonal transport in branches that will subsequently dismantle...
November 23, 2016: Neuron
https://www.readbyqxmd.com/read/27736876/dbo-henji-modulates-synaptic-dpak-to-gate-glutamate-receptor-abundance-and-postsynaptic-response
#7
Manyu Wang, Pei-Yi Chen, Chien-Hsiang Wang, Tzu-Ting Lai, Pei-I Tsai, Ying-Ju Cheng, Hsiu-Hua Kao, Cheng-Ting Chien
In response to environmental and physiological changes, the synapse manifests plasticity while simultaneously maintains homeostasis. Here, we analyzed mutant synapses of henji, also known as dbo, at the Drosophila neuromuscular junction (NMJ). In henji mutants, NMJ growth is defective with appearance of satellite boutons. Transmission electron microscopy analysis indicates that the synaptic membrane region is expanded. The postsynaptic density (PSD) houses glutamate receptors GluRIIA and GluRIIB, which have distinct transmission properties...
October 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27698419/x-ray-structure-of-the-human-%C3%AE-4%C3%AE-2-nicotinic-receptor
#8
Claudio L Morales-Perez, Colleen M Noviello, Ryan E Hibbs
Nicotinic acetylcholine receptors are ligand-gated ion channels that mediate fast chemical neurotransmission at the neuromuscular junction and have diverse signalling roles in the central nervous system. The nicotinic receptor has been a model system for cell-surface receptors, and specifically for ligand-gated ion channels, for well over a century. In addition to the receptors' prominent roles in the development of the fields of pharmacology and neurobiology, nicotinic receptors are important therapeutic targets for neuromuscular disease, addiction, epilepsy and for neuromuscular blocking agents used during surgery...
October 20, 2016: Nature
https://www.readbyqxmd.com/read/27687289/progression-of-motor-neuron-disease-is-accelerated-and-the-ability-to-recover-is-compromised-with-advanced-age-in-rnls8-mice
#9
Krista J Spiller, Clark R Restrepo, Tahiyana Khan, Anna M Stieber, Linda K Kwong, John Q Trojanowski, Virginia M-Y Lee
In order to treat progressive paralysis in ALS patients, it is critical to develop a mouse that closely models human ALS in both pathology and also in the timing of these events. We have recently generated new TDP-43 bigenic mice (called rNLS8) with doxycycline (Dox)-suppressible expression of human TDP-43 (hTDP-43) harboring a defective nuclear localization signal (hTDP-43∆NLS) under the control of the NEFH promoter. Our previous studies characterized the pathology and disease course in young rNLS8 mice following induction of neuronal hTDP-43ΔNLS...
September 29, 2016: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/27676961/physiological-anatomy-of-botulinum-toxin-effect-on-the-spastic-muscle-of-children-with-cerebral-palsy
#10
Claire Mietton, Laurent Schaeffer, Nathalie Streichenberger, Vincent Cunin, Berrouz Kassai, Isabelle Poirot
OBJECTIVE: Botulinum toxin is one of the treatments available to treat spasticity in patients with cerebral palsy (CP) from 2 years of age. The long-term action of the toxin on the neuromuscular junction (NMJ) and muscle structure is still unknown. We formulated the hypothesis that repeated injections of botulinum toxin could modify muscle structure. The main aim of our 3-year monocentric descriptive study is to evaluate the long-term effect of repeated injections of botulinum toxin on the muscle and the neuromuscular junction in patients with CP...
September 2016: Annals of Physical and Rehabilitation Medicine
https://www.readbyqxmd.com/read/27650259/expression-of-cys-loop-receptor-subunits-and-acetylcholine-binding-protein-in-the-mechanosensory-neurons-glial-cells-and-muscle-tissue-of-the-spider-cupiennius-salei
#11
Hongxia Liu, Andrew S French, Päivi H Torkkeli
The spider, Cupiennius salei, central and peripheral nervous system transcriptomes have 15 Cys-loop receptor subunits and an acetylcholine binding protein (AChBP). Twelve subunits are predicted to form anion channels gated by γ-aminobutyric acid (GABA), glutamate, histamine or changes in pH, and three are putative ACh gated cation channels. Spiders have a variety of mechanosensilla and proprioceptive organs that are innervated by efferents in their peripherally located parts, and efferents also innervate muscle fibers...
September 21, 2016: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/27596971/reappraisal-of-vacht-cre-preference-in-slow-motor-neurons-innervating-type-i-or-iia-muscle-fibers
#12
Hidemi Misawa, Daijiro Inomata, Miseri Kikuchi, Sae Maruyama, Yasuhiro Moriwaki, Takashi Okuda, Nobuyuki Nukina, Tomoyuki Yamanaka
VAChT-Cre.Fast and VAChT-Cre.Slow mice selectively express Cre recombinase in approximately one half of postnatal somatic motor neurons. The mouse lines have been used in various studies with selective genetic modifications in adult motor neurons. In the present study, we crossed VAChT-Cre lines with a reporter line, CAG-Syp/tdTomato, in which synaptophysin-tdTomato fusion proteins are efficiently sorted to axon terminals, making it possible to label both cell bodies and axon terminals of motor neurons. In the mice, Syp/tdTomato fluorescence preferentially co-localized with osteopontin, a recently discovered motor neuron marker for slow-twitch fatigue-resistant (S) and fast-twitch fatigue-resistant (FR) types...
November 2016: Genesis: the Journal of Genetics and Development
https://www.readbyqxmd.com/read/27580012/constitutively-low-expression-of-collagen-xiii-alpha-1-may-help-explain-the-vulnerability-of-the-inferior-rectus-muscle-to-thyroid-associated-ophthalmopathy
#13
Olivia Claire Morris, Kirsten Schebitz Walter, Esbjörn Telemo, Christoph Hintschich
Thyroid-associated ophthalmopathy (TAO) has a predilection for inferior rectus muscle that has never been explained. We conducted immunohistochemical staining for the soluble cleaved form of collagen XIII alpha 1 (COL13A1) and found constitutively low expression of COL13A1 in normal human inferior rectus muscles and moderate expression of COL13A1 in normal human medial rectus muscles. COL13A1 is known to be essential to development and maintenance of neuromuscular junctions and there is some evidence to suggest it may help support normal immune function...
December 2016: Orbit
https://www.readbyqxmd.com/read/27504085/the-presynaptic-microtubule-cytoskeleton-in-physiological-and-pathological-conditions-lessons-from-drosophila-fragile-x-syndrome-and-hereditary-spastic-paraplegias
#14
REVIEW
Felipe J Bodaleo, Christian Gonzalez-Billault
The capacity of the nervous system to generate neuronal networks relies on the establishment and maintenance of synaptic contacts. Synapses are composed of functionally different presynaptic and postsynaptic compartments. An appropriate synaptic architecture is required to provide the structural basis that supports synaptic transmission, a process involving changes in cytoskeletal dynamics. Actin microfilaments are the main cytoskeletal components present at both presynaptic and postsynaptic terminals in glutamatergic synapses...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/27493991/microfluidic-device-for-the-formation-of-optically-excitable-three-dimensional-compartmentalized-motor-units
#15
Sebastien G M Uzel, Randall J Platt, Vidya Subramanian, Taylor M Pearl, Christopher J Rowlands, Vincent Chan, Laurie A Boyer, Peter T C So, Roger D Kamm
Motor units are the fundamental elements responsible for muscle movement. They are formed by lower motor neurons and their muscle targets, synapsed via neuromuscular junctions (NMJs). The loss of NMJs in neurodegenerative disorders (such as amyotrophic lateral sclerosis or spinal muscle atrophy) or as a result of traumatic injuries affects millions of lives each year. Developing in vitro assays that closely recapitulate the physiology of neuromuscular tissues is crucial to understand the formation and maturation of NMJs, as well as to help unravel the mechanisms leading to their degeneration and repair...
August 2016: Science Advances
https://www.readbyqxmd.com/read/27459966/the-influence-of-postsynaptic-structure-on-missing-quanta-at-the-drosophila-neuromuscular-junction
#16
Christine T Nguyen, Bryan A Stewart
BACKGROUND: Synaptic transmission requires both pre- and post-synaptic elements for neural communication. The postsynaptic structure contributes to the ability of synaptic currents to induce voltage changes in postsynaptic cells. At the Drosophila neuromuscular junction (NMJ), the postsynaptic structure, known as the subsynaptic reticulum (SSR), consists of elaborate membrane folds that link the synaptic contacts to the muscle, but its role in synaptic physiology is poorly understood...
2016: BMC Neuroscience
https://www.readbyqxmd.com/read/27413149/compartmentalized-regulation-of-parkin-mediated-mitochondrial-quality-control-in-the-drosophila-nervous-system-in-vivo
#17
Hyun Sung, Lauren C Tandarich, Kenny Nguyen, Peter J Hollenbeck
UNLABELLED: In neurons, the normal distribution and selective removal of mitochondria are considered essential for maintaining the functions of the large asymmetric cell and its diverse compartments. Parkin, a E3 ubiquitin ligase associated with familial Parkinson's disease, has been implicated in mitochondrial dynamics and removal in cells including neurons. However, it is not clear how Parkin functions in mitochondrial turnover in vivo, or whether Parkin-dependent events of the mitochondrial life cycle occur in all neuronal compartments...
July 13, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27408701/pathogenesis-of-myasthenia-gravis-update-on-disease-types-models-and-mechanisms
#18
REVIEW
William D Phillips, Angela Vincent
Myasthenia gravis is an autoimmune disease of the neuromuscular junction (NMJ) caused by antibodies that attack components of the postsynaptic membrane, impair neuromuscular transmission, and lead to weakness and fatigue of skeletal muscle. This can be generalised or localised to certain muscle groups, and involvement of the bulbar and respiratory muscles can be life threatening. The pathogenesis of myasthenia gravis depends upon the target and isotype of the autoantibodies. Most cases are caused by immunoglobulin (Ig)G1 and IgG3 antibodies to the acetylcholine receptor (AChR)...
2016: F1000Research
https://www.readbyqxmd.com/read/27197982/human-senataxin-modulates-structural-plasticity-of-the-neuromuscular-junction-in-drosophila-through-a-neuronally-conserved-tgf%C3%AE-signalling-pathway
#19
Zeeshan Mushtaq, Saumitra Dey Choudhury, Sri Krishna Gangwar, Genny Orso, Vimlesh Kumar
BACKGROUND: Mutations in the human Senataxin (hSETX) gene have been shown to cause two forms of neurodegenerative disorders - a dominant form called amyotrophic lateral sclerosis type 4 (ALS4) and a recessive form called ataxia with oculomotor apraxia type 2 (AOA2). SETX is a putative DNA/RNA helicase involved in RNA metabolism. Although several dominant mutations linked with ALS4 have been identified in SETX, their contribution towards ALS4 pathophysiology is still elusive. METHOD: In order to model ALS4 in Drosophila and to elucidate the morphological, physiological and signalling consequences, we overexpressed the wild-type and pathological forms of hSETX in Drosophila...
2016: Neuro-degenerative Diseases
https://www.readbyqxmd.com/read/27069119/functional-characterization-of-orbicularis-oculi-and-extraocular-muscles
#20
Marijana Sekulic-Jablanovic, Nina D Ullrich, David Goldblum, Anja Palmowski-Wolfe, Francesco Zorzato, Susan Treves
The orbicularis oculi are the sphincter muscles of the eyelids and are involved in modulating facial expression. They differ from both limb and extraocular muscles (EOMs) in their histology and biochemistry. Weakness of the orbicularis oculi muscles is a feature of neuromuscular disorders affecting the neuromuscular junction, and weakness of facial muscles and ptosis have also been described in patients with mutations in the ryanodine receptor gene. Here, we investigate human orbicularis oculi muscles and find that they are functionally more similar to quadriceps than to EOMs in terms of excitation-contraction coupling components...
May 2016: Journal of General Physiology
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