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neuromuscular junction physiology

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https://www.readbyqxmd.com/read/27810937/deficiency-of-cpeb2-confined-chat-expression-in-the-dorsal-motor-nucleus-of-vagus-causes-hyperactivated-parasympathetic-signaling-associated-bronchoconstriction
#1
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 knockout (KO) mice and found that most died within 3 days after birth. CPEB2 is highly expressed in the brainstem, which controls vital functions like breathing. Whole-body plethysmography revealed that KO neonates had aberrant respiration with frequent apnea. Nevertheless, the morphology and function of respiratory rhythm generator and diaphragm neuromuscular junctions appeared normal...
November 3, 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
#2
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
#3
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
#4
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 3, 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
#5
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
#6
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
#7
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
#8
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
#9
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...
August 31, 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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
https://www.readbyqxmd.com/read/27016366/modelling-the-response-to-low-frequency-repetitive-nerve-stimulation-of-myasthenia-gravis-and-lambert-eaton-myasthenic-syndrome
#17
Francesc Miralles
Myasthenia gravis (MG) is an autoimmune postsynaptic disorder of neuromuscular transmission caused, in most patients, by antibodies against postsynaptic acetylcholine receptors. Lambert-Eaton myasthenic syndrome (LEMS) is a presynaptic autoimmune disease in which there is a reduction in Ca(2+) entry with each impulse due to the action of antibodies against Ca(2+) channels. These diseases have a distinct pattern of response to low-frequency repetitive nerve stimulation which allows its recognition in a particular subject...
March 25, 2016: Medical & Biological Engineering & Computing
https://www.readbyqxmd.com/read/26955780/synaptic-abnormalities-of-mice-lacking-toll-like-receptor-tlr-9
#18
V Patel, A M Patel, J J McArdle
Motor, sensory, and autonomic abnormalities are reported for toll-like receptor 9 (TLR9) knock-out (KO) mice. However, a physiological role of TLR9 in the nervous system is largely unknown. Since altered synaptic transmission can contribute to sensory and motor abnormalities, we evaluated neuromuscular junction (NMJ) function and morphology of TLR9 KO mice. Triangularis sterni nerve-muscle preparations were dissected from TLR9 KO and age-matched control mice. Two-electrode voltage clamp of the motor endplate revealed that the amplitude and frequency of miniature end plate currents (mEPCs) for TLR9 KO NMJs were significantly greater than control...
June 2, 2016: Neuroscience
https://www.readbyqxmd.com/read/26901416/c-terminal-src-kinase-gates-homeostatic-synaptic-plasticity-and-regulates-fasciclin-ii-expression-at-the-drosophila-neuromuscular-junction
#19
Ashlyn M Spring, Douglas J Brusich, C Andrew Frank
Forms of homeostatic plasticity stabilize neuronal outputs and promote physiologically favorable synapse function. A well-studied homeostatic system operates at the Drosophila melanogaster larval neuromuscular junction (NMJ). At the NMJ, impairment of postsynaptic glutamate receptor activity is offset by a compensatory increase in presynaptic neurotransmitter release. We aim to elucidate how this process operates on a molecular level and is preserved throughout development. In this study, we identified a tyrosine kinase-driven signaling system that sustains homeostatic control of NMJ function...
February 2016: PLoS Genetics
https://www.readbyqxmd.com/read/26869891/neuromuscular-junctions-as-key-contributors-and-therapeutic-targets-in-spinal-muscular-atrophy
#20
REVIEW
Marina Boido, Alessandro Vercelli
Spinal muscular atrophy (SMA) is a recessive autosomal neuromuscular disease, representing the most common fatal pediatric pathology. Even though, classically and in a simplistic way, it is categorized as a motor neuron (MN) disease, there is an increasing general consensus that its pathogenesis is more complex than expected. In particular, neuromuscular junctions (NMJs) are affected by dramatic alterations, including immaturity, denervation and neurofilament accumulation, associated to impaired synaptic functions: these abnormalities may in turn have a detrimental effect on MN survival...
2016: Frontiers in Neuroanatomy
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