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https://www.readbyqxmd.com/read/27927794/nmj-morph-reveals-principal-components-of-synaptic-morphology-influencing-structure-function-relationships-at-the-neuromuscular-junction
#1
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/27916456/acute-fasting-regulates-retrograde-synaptic-enhancement-through-a-4e-bp-dependent-mechanism
#2
Grant Kauwe, Kazuya Tsurudome, Jay Penney, Megumi Mori, Lindsay Gray, Mario R Calderon, Fatima Elazouzzi, Nicole Chicoine, Nahum Sonenberg, A Pejmun Haghighi
While beneficial effects of fasting on organismal function and health are well appreciated, we know little about the molecular details of how fasting influences synaptic function and plasticity. Our genetic and electrophysiological experiments demonstrate that acute fasting blocks retrograde synaptic enhancement that is normally triggered as a result of reduction in postsynaptic receptor function at the Drosophila larval neuromuscular junction (NMJ). This negative regulation critically depends on transcriptional enhancement of eukaryotic initiation factor 4E binding protein (4E-BP) under the control of the transcription factor Forkhead box O (Foxo)...
November 21, 2016: Neuron
https://www.readbyqxmd.com/read/27906081/vacht-overexpression-increases-acetylcholine-at-the-synaptic-cleft-and-accelerates-aging-of-neuromuscular-junctions
#3
Satoshi Sugita, Leland L Fleming, Caleb Wood, Sydney K Vaughan, Matheus P S M Gomes, Wallace Camargo, Ligia A Naves, Vania F Prado, Marco A M Prado, Cristina Guatimosim, Gregorio Valdez
BACKGROUND: Cholinergic dysfunction occurs during aging and in a variety of diseases, including amyotrophic lateral sclerosis (ALS). However, it remains unknown whether changes in cholinergic transmission contributes to age- and disease-related degeneration of the motor system. Here we investigated the effect of moderately increasing levels of synaptic acetylcholine (ACh) on the neuromuscular junction (NMJ), muscle fibers, and motor neurons during development and aging and in a mouse model for amyotrophic lateral sclerosis (ALS)...
October 5, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27895925/somatic-neural-alterations-in-non-diabetic-obesity-a-cross-sectional-study
#4
Ram Lochan Yadav, Deepak Sharma, Prakash Kumar Yadav, Dev Kumar Shah, Kopila Agrawal, Rita Khadka, Md Nazrul Islam
BACKGROUND: Reports on alterations in somatic neural functions due to non-diabetic obesity, a major risk factor for diabetes, are few and still a matter of debate. Nevertheless, to our knowledge, reports lack any comments on the type of somatic nerve fibers affected in non-diabetic obesity. Therefore, this study aimed to find out the alteration in somatic neural functions in non-diabetic obese persons if any. METHODS: The study was conducted on 30 adult non-diabetic obese persons (mean age 32...
2016: BMC Obesity
https://www.readbyqxmd.com/read/27863479/myasthenic-symptoms-in-anti-low-density-lipoprotein-receptor-related-protein-4-antibody-seropositive-amyotrophic-lateral-sclerosis-two-case-reports
#5
Hisashi Takahashi, Yu-Ichi Noto, Naoki Makita, Yukie Kushimura-Okada, Ryotaro Ishii, Akihiro Tanaka, Tomoyuki Ohara, Shunya Nakane, Osamu Higuchi, Masanori Nakagawa, Toshiki Mizuno
BACKGROUND: Myasthenic symptoms can be present in patients with amyotrophic lateral sclerosis (ALS). These symptoms have been considered to be caused by the degeneration of distal motor neurons and the neuromuscular junction (NMJ). Recent studies suggested that antibody to low-density lipoprotein receptor-related protein 4 (LRP4) was a pathogenic agent of myasthenia gravis (MG), and it was also detected in ALS patients. CASE PRESENTATION: Patient 1: A 58-year-old Japanese man developed progressive weakness and subsequent myasthenic symptoms including oculomotor disturbance...
November 18, 2016: BMC Neurology
https://www.readbyqxmd.com/read/27770767/mical-like-regulates-fasciclin-ii-membrane-cycling-and-synaptic-development
#6
Minyeop Nahm, Sunyoung Park, Jihye Lee, Seungbok Lee
Fasciclin II (FasII), the Drosophila ortholog of neural cell adhesion molecule (NCAM), plays a critical role in synaptic stabilization and plasticity. Although this molecule undergoes constitutive cycling at the synaptic membrane, how its membrane trafficking is regulated to ensure proper synaptic development remains poorly understood. In a genetic screen, we recovered a mutation in Drosophila mical-like that displays an increase in bouton numbers and a decrease in FasII levels at the neuromuscular junction (NMJ)...
October 2016: Molecules and Cells
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/27734846/fe65-and-fe65l1-share-common-synaptic-functions-and-genetically-interact-with-the-app-family-in-neuromuscular-junction-formation
#8
Paul Strecker, Susann Ludewig, Marco Rust, Tabea A Mundinger, Andreas Görlich, Elisa G Krächan, Christina Mehrfeld, Joachim Herz, Martin Korte, Suzanne Y Guénette, Stefan Kins
The FE65 adaptor proteins (FE65, FE65L1 and FE65L2) bind proteins that function in diverse cellular pathways and are essential for specific biological processes. Mice lacking both FE65 and FE65L1 exhibit ectopic neuronal positioning in the cortex and muscle weakness. p97FE65-KO mice, expressing a shorter FE65 isoform able to bind amyloid precursor protein family members (APP, APLP1, APLP2), develop defective long-term potentiation (LTP) and aged mice display spatial learning and memory deficits that are absent from young mice...
May 11, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27717377/immune-response-in-peripheral-axons-delays-disease-progression-in-sod1-g93a-mice
#9
Giovanni Nardo, Maria Chiara Trolese, Giuseppe de Vito, Roberta Cecchi, Nilo Riva, Giorgia Dina, Paul R Heath, Angelo Quattrini, Pamela J Shaw, Vincenzo Piazza, Caterina Bendotti
BACKGROUND: Increasing evidence suggests that the immune system has a beneficial role in the progression of amyotrophic lateral sclerosis (ALS) although the mechanism remains unclear. Recently, we demonstrated that motor neurons (MNs) of C57SOD1(G93A) mice with slow disease progression activate molecules classically involved in the cross-talk with the immune system. This happens a lot less in 129SvSOD1(G93A) mice which, while expressing the same amount of transgene, had faster disease progression and earlier axonal damage...
October 7, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27713817/vacht-overexpression-increases-acetylcholine-at-the-synaptic-cleft-and-accelerates-aging-of-neuromuscular-junctions
#10
Satoshi Sugita, Leland L Fleming, Caleb Wood, Sydney K Vaughan, Matheus P S M Gomes, Wallace Camargo, Ligia A Naves, Vania F Prado, Marco A M Prado, Cristina Guatimosim, Gregorio Valdez
BACKGROUND: Cholinergic dysfunction occurs during aging and in a variety of diseases, including amyotrophic lateral sclerosis (ALS). However, it remains unknown whether changes in cholinergic transmission contributes to age- and disease-related degeneration of the motor system. Here we investigated the effect of moderately increasing levels of synaptic acetylcholine (ACh) on the neuromuscular junction (NMJ), muscle fibers, and motor neurons during development and aging and in a mouse model for amyotrophic lateral sclerosis (ALS)...
2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27711243/cgmp-dependent-protein-kinase-inhibition-extends-the-upper-temperature-limit-of-stimulus-evoked-calcium-responses-in-motoneuronal-boutons-of-drosophila-melanogaster-larvae
#11
Jennifer L Krill, Ken Dawson-Scully
While the mammalian brain functions within a very narrow range of oxygen concentrations and temperatures, the fruit fly, Drosophila melanogaster, has employed strategies to deal with a much wider range of acute environmental stressors. The foraging (for) gene encodes the cGMP-dependent protein kinase (PKG), has been shown to regulate thermotolerance in many stress-adapted species, including Drosophila, and could be a potential therapeutic target in the treatment of hyperthermia in mammals. Whereas previous thermotolerance studies have looked at the effects of PKG variation on Drosophila behavior or excitatory postsynaptic potentials at the neuromuscular junction (NMJ), little is known about PKG effects on presynaptic mechanisms...
2016: PloS One
https://www.readbyqxmd.com/read/27676961/physiological-anatomy-of-botulinum-toxin-effect-on-the-spastic-muscle-of-children-with-cerebral-palsy
#12
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/27666825/musk-kinase-activity-is-modulated-by-a-serine-phosphorylation-site-in-the-kinase-loop
#13
B Z Camurdanoglu, C Hrovat, G Dürnberger, M Madalinski, K Mechtler, R Herbst
The neuromuscular junction (NMJ) forms when a motor neuron contacts a muscle fibre. A reciprocal exchange of signals initiates a cascade of signalling events that result in pre- and postsynaptic differentiation. At the centre of these signalling events stands muscle specific kinase (MuSK). MuSK activation, kinase activity and subsequent downstream signalling are crucial for NMJ formation as well as maintenance. Therefore MuSK kinase activity is tightly regulated to ensure proper NMJ development. We have identified a novel serine phosphorylation site at position 751 in MuSK that is increasingly phosphorylated upon agrin stimulation...
September 26, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27641118/a-novel-approach-for-targeted-delivery-to-motoneurons-using-cholera-toxin-b-modified-protocells
#14
Maria A Gonzalez Porras, Paul N Durfee, Ashley M Gregory, Gary C Sieck, C Jeffrey Brinker, Carlos B Mantilla
BACKGROUND: Trophic interactions between muscle fibers and motoneurons at the neuromuscular junction (NMJ) play a critical role in determining motor function throughout development, aging, injury, or disease. Treatment of neuromuscular disorders is hindered by the inability to selectively target motoneurons with pharmacological and genetic interventions. NEW METHOD: We describe a novel delivery system to motoneurons using mesoporous silica nanoparticles encapsulated within a lipid bilayer (protocells) and modified with the atoxic subunit B of the cholera toxin (CTB) that binds to gangliosides present on neuronal membranes...
September 15, 2016: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/27633977/new-perspectives-on-amyotrophic-lateral-sclerosis-the-role-of-glial-cells-at-the-neuromuscular-junction
#15
Danielle Arbour, Christine Vande Velde, Richard Robitaille
Amyotrophic lateral sclerosis (ALS) is a disease leading to the death of motor neurons (MNs). It is also recognized as a non-cell autonomous disease where glial cells in the CNS are involved in its pathogenesis and progression. However, although denervation of neuromuscular junctions (NMJs) represents an early and major event in ALS, the importance of glial cells at this synapse receives little attention. An interesting possibility is that altered relationships between glial cells and MNs in the spinal cord in ALS may also take place at the NMJ...
September 16, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27614294/the-role-of-laminins-in-the-organization-and-function-of-neuromuscular-junctions
#16
Robert S Rogers, Hiroshi Nishimune
The synapse between motor neurons and skeletal muscle is known as the neuromuscular junction (NMJ). Proper alignment of presynaptic and post-synaptic structures of motor neurons and muscle fibers, respectively, is essential for efficient motor control of skeletal muscles. The synaptic cleft between these two cells is filled with basal lamina. Laminins are heterotrimer extracellular matrix molecules that are key members of the basal lamina. Laminin α4, α5, and β2 chains specifically localize to NMJs, and these laminin isoforms play a critical role in maintenance of NMJs and organization of synaptic vesicle release sites known as active zones...
September 7, 2016: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/27611986/neuromuscular-transmission-abnormalities-in-myotonic-dystrophy-type-1-a-neurophysiological-study
#17
Francesco Bombelli, Ludovico Lispi, Sandro Costanzi Porrini, Manlio Giacanelli, Chiara Terracciano, Roberto Massa, Antonio Petrucci
OBJECTIVES: Weakness and fatigue are frequent symptoms in myotonic dystrophy type 1 (DM1), mainly as a result of muscle impairment. However, neuromuscular junction (NMJ) abnormalities could play an additional role in determining these manifestations. We aimed to document the possible NMJ involvement in DM1. PATIENTS AND METHODS: In order to substantiate this hypothesis we performed low rate repetitive nerve stimulation (RNS) and single fiber electromyography (SFEMG), in 14 DM1 subjects...
November 2016: Clinical Neurology and Neurosurgery
https://www.readbyqxmd.com/read/27585036/the-fibular-nerve-injury-method-a-reliable-assay-to-identify-and-test-factors-that-repair-neuromuscular-junctions
#18
William Dalkin, Thomas Taetzsch, Gregorio Valdez
The neuromuscular junction (NMJ) undergoes deleterious structural and functional changes as a result of aging, injury and disease. Thus, it is imperative to understand the cellular and molecular changes involved in maintaining and repairing NMJs. For this purpose, we have developed a method to reliably and consistently examine regenerating NMJs in mice. This nerve injury method involves crushing the common fibular nerve as it passes over the lateral head of the gastrocnemius muscle tendon near the knee. Using 70 day old female mice, we demonstrate that motor axons begin to reinnervate previous postsynaptic targets within 7 days post-crush...
2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27569547/impaired-presynaptic-high-affinity-choline-transporter-causes-a-congenital-myasthenic-syndrome-with-episodic-apnea
#19
Stéphanie Bauché, Seana O'Regan, Yoshiteru Azuma, Fanny Laffargue, Grace McMacken, Damien Sternberg, Guy Brochier, Céline Buon, Nassima Bouzidi, Ana Topf, Emmanuelle Lacène, Ganaelle Remerand, Anne-Marie Beaufrere, Céline Pebrel-Richard, Julien Thevenon, Salima El Chehadeh-Djebbar, Laurence Faivre, Yannis Duffourd, Federica Ricci, Tiziana Mongini, Chiara Fiorillo, Guja Astrea, Carmen Magdalena Burloiu, Niculina Butoianu, Carmen Sandu, Laurent Servais, Gisèle Bonne, Isabelle Nelson, Isabelle Desguerre, Marie-Christine Nougues, Benoit Bœuf, Norma Romero, Jocelyn Laporte, Anne Boland, Doris Lechner, Jean-François Deleuze, Bertrand Fontaine, Laure Strochlic, Hanns Lochmuller, Bruno Eymard, Michèle Mayer, Sophie Nicole
The neuromuscular junction (NMJ) is one of the best-studied cholinergic synapses. Inherited defects of peripheral neurotransmission result in congenital myasthenic syndromes (CMSs), a clinically and genetically heterogeneous group of rare diseases with fluctuating fatigable muscle weakness as the clinical hallmark. Whole-exome sequencing and Sanger sequencing in six unrelated families identified compound heterozygous and homozygous mutations in SLC5A7 encoding the presynaptic sodium-dependent high-affinity choline transporter 1 (CHT), which is known to be mutated in one dominant form of distal motor neuronopathy (DHMN7A)...
September 1, 2016: American Journal of Human Genetics
https://www.readbyqxmd.com/read/27567686/presynaptic-camkii-regulates-activity-dependent-axon-terminal-growth
#20
Katherine R Nesler, Emily L Starke, Nathan G Boin, Matthew Ritz, Scott A Barbee
Spaced synaptic depolarization induces rapid axon terminal growth and the formation of new synaptic boutons at the Drosophila larval neuromuscular junction (NMJ). Here, we identify a novel presynaptic function for the Calcium/Calmodulin-dependent Kinase II (CamKII) protein in the control of activity-dependent synaptic growth. Consistent with this function, we find that both total and phosphorylated CamKII (p-CamKII) are enriched in axon terminals. Interestingly, p-CamKII appears to be enriched at the presynaptic axon terminal membrane...
October 2016: Molecular and Cellular Neurosciences
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