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Neuromuscular junction

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https://www.readbyqxmd.com/read/28449366/moving-forward-with-the-neuromuscular-junction
#1
REVIEW
Claire Legay, Lin Mei
The neuromuscular junction (NMJ) is indispensable for survival. This synapse between motoneurons and skeletal muscle fibers allows posture, movement and respiration. Therefore, its dysfunction creates pathologies than can be lethal. The molecular mechanisms of NMJ development and maintenance are the subject of intensive studies. This mini-review focuses on some of the most recent discoveries. An unexpected role for a protein, rapsyn, which has been known for 40 years to aggregate acetylcholine receptors has emerged...
April 27, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28446779/functional-neuronal-differentiation-of-injury-induced-muscle-derived-stem-cell-like-cells-with-therapeutic-implications
#2
Kinga Vojnits, Haiying Pan, Xiaojing Dai, Hao Sun, Qingchun Tong, Radbod Darabi, Johnny Huard, Yong Li
Mammalian skeletal muscles contain a number of heterogeneous cell populations. Our previous study characterized a unique population of myogenic lineage stem cells that can be isolated from adult mammalian skeletal muscles upon injury. These injury-induced muscle-derived stem cell-like cells (iMuSCs) displayed a multipotent state with sensitiveness and strong migration abilities. Here, we report that these iMuSCs have the capability to form neurospheres that represent multiple neural phenotypes. The induced neuronal cells expressed various neuron-specific proteins, their mRNA expression during neuronal differentiation recapitulated embryonic neurogenesis, they generated action potentials, and they formed functional synapses in vitro...
April 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28445884/synergistic-action-of-presynaptic-muscarinic-acetylcholine-receptors-and-adenosine-receptors-in-developmental-axonal-competition-at-the-neuromuscular-junction
#3
Laura Nadal, Neus Garcia, Erica Hurtado, Anna Simó, Marta Tomàs, Maria Angel Lanuza, Victor Cilleros, Josep Maria Tomàs
The development of the nervous system involves the initial overproduction of synapses, which promotes connectivity. Hebbian competition between axons with different activities leads to the loss of roughly half of the overproduced elements and this refines connectivity. We used quantitative immunohistochemistry to investigate, in the postnatal day 7 (P7) to P9 neuromuscular junctions, the involvement of muscarinic receptors (muscarinic acetylcholine autoreceptors and the M1, M2, and M4 subtypes) and adenosine receptors (A1 and A2A subtypes) in the control of axonal elimination after the mouse levator auris longus muscle had been exposed to selective antagonists in vivo...
April 27, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28444917/ultrastructural-comparison-of-the-drosophila-larval-and-adult-ventral-abdominal-neuromuscular-junction
#4
Nicole Wagner
Drosophila melanogaster has recently emerged as model system for studying synaptic transmission and plasticity during adulthood, aging and neurodegeneration. However, still little is known about the basic neuronal mechanisms of synaptic function in the adult fly. Per se, adult Drosophila neuromuscular junctions should be highly suited for studying these aspects as they allow for genetic manipulations in combination with ultrastructural and electrophysiological analyses. Although different neuromuscular junctions of the adult fly have been described during the last years, a direct ultrastructural comparison with their larval counterpart is lacking...
April 26, 2017: Journal of Morphology
https://www.readbyqxmd.com/read/28444817/microtubule-stabilization-promoted-axonal-regeneration-and-functional-recovery-after-spinal-root-avulsion
#5
Heng Li, Wutian Wu
A spinal root avulsion injury disconnects spinal roots with the spinal cord. The rampant motoneuron death, inhibitory CNS/PNS transitional zone (TZ) for axonal regrowth and limited regeneration speed together lead to motor dysfunction. Microtubules rearrange to assemble a new growth cone and disorganized microtubules underline regeneration failure. It's been shown that microtubule-stabilizing drug, Epothilone B, enhanced axonal regeneration and attenuated fibrotic scaring after spinal cord injury. Here, we are reporting that after spinal root avulsion+ re-implantation in adult rats, EpoB treatment improved motor functional recovery and potentiated electrical responses of motor units...
April 26, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28442746/ultrastructural-characterization-of-the-lower-motor-system-in-a-mouse-model-of-krabbe-disease
#6
Valentina Cappello, Laura Marchetti, Paola Parlanti, Silvia Landi, Ilaria Tonazzini, Marco Cecchini, Vincenzo Piazza, Mauro Gemmi
Krabbe disease (KD) is a neurodegenerative disorder caused by the lack of β- galactosylceramidase enzymatic activity and by widespread accumulation of the cytotoxic galactosyl-sphingosine in neuronal, myelinating and endothelial cells. Despite the wide use of Twitcher mice as experimental model for KD, the ultrastructure of this model is partial and mainly addressing peripheral nerves. More details are requested to elucidate the basis of the motor defects, which are the first to appear during KD onset. Here we use transmission electron microscopy (TEM) to focus on the alterations produced by KD in the lower motor system at postnatal day 15 (P15), a nearly asymptomatic stage, and in the juvenile P30 mouse...
December 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/28441759/synaptic-homeostasis-and-its-immunological-disturbance-in-neuromuscular-junction-disorders
#7
REVIEW
Masaharu Takamori
In the neuromuscular junction, postsynaptic nicotinic acetylcholine receptor (nAChR) clustering, trans-synaptic communication and synaptic stabilization are modulated by the molecular mechanisms underlying synaptic plasticity. The synaptic functions are based presynaptically on the active zone architecture, synaptic vesicle proteins, Ca(2+) channels and synaptic vesicle recycling. Postsynaptically, they are based on rapsyn-anchored nAChR clusters, localized sensitivity to ACh, and synaptic stabilization via linkage to the extracellular matrix so as to be precisely opposed to the nerve terminal...
April 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28433752/serotonergic-transmission-and-gap-junctional-coupling-in-proventricular-muscle-cells-in-the-american-cockroach-periplaneta-americana
#8
Ryoichi Yoshimura, Taeko Suetsugu, Yasuhisa Endo
The visceral muscle tissues of insects consist of striated muscle cells. The mechanisms responsible for delivering signals to the contractile muscles in the insect digestive tract remain unclear. We found that serotonergic nerves innervate the hemocoel surfaces of foregut and midgut muscles in the American cockroach. Electron microscopy of the neuromuscular junctions in the proventriculus (gizzard) revealed typical synaptic structures, the accumulation of large core/cored vesicles (neuropeptides) and small clear vesicle (neurotransmitter) at presynapses, and synaptic clefts...
April 19, 2017: Journal of Insect Physiology
https://www.readbyqxmd.com/read/28428759/morphological-regeneration-and-functional-recovery-of-neuromuscular-junctions-after-tourniquet-induced-injuries-in-mouse-hindlimb
#9
Huiyin Tu, Dongze Zhang, Ryan M Corrick, Robert L Muelleman, Michael C Wadman, Yu-Long Li
Tourniquet application and its subsequent release cause serious injuries to the skeletal muscle, nerve, and neuromuscular junction (NMJ) due to mechanical compression and ischemia-reperfusion (IR). Monitoring structural and functional repair of the NMJ, nerve, and skeletal muscle after tourniquet-induced injuries is beneficial in exploring potential cellular and molecular mechanisms responsible for tourniquet-induced injuries, and for establishing effective therapeutic interventions. Here, we observed long-term morphological and functional changes of the NMJ in a murine model of tourniquet-induced hindlimb injuries...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28422078/antivenom-for-neuromuscular-paralysis-resulting-from-snake-envenoming
#10
REVIEW
Anjana Silva, Wayne C Hodgson, Geoffrey K Isbister
Antivenom therapy is currently the standard practice for treating neuromuscular dysfunction in snake envenoming. We reviewed the clinical and experimental evidence-base for the efficacy and effectiveness of antivenom in snakebite neurotoxicity. The main site of snake neurotoxins is the neuromuscular junction, and the majority are either: (1) pre-synaptic neurotoxins irreversibly damaging the presynaptic terminal; or (2) post-synaptic neurotoxins that bind to the nicotinic acetylcholine receptor. Pre-clinical tests of antivenom efficacy for neurotoxicity include rodent lethality tests, which are problematic, and in vitro pharmacological tests such as nerve-muscle preparation studies, that appear to provide more clinically meaningful information...
April 19, 2017: Toxins
https://www.readbyqxmd.com/read/28419739/cardiac-troponin-t-and-fast-skeletal-muscle-denervation-in-ageing
#11
Zherong Xu, Xin Feng, Juan Dong, Zhong-Min Wang, Jingyun Lee, Cristina Furdui, Daniel Clark Files, Kristen M Beavers, Stephen Kritchevsky, Carolanne Milligan, Jian-Ping Jin, Osvaldo Delbono, Tan Zhang
BACKGROUND: Ageing skeletal muscle undergoes chronic denervation, and the neuromuscular junction (NMJ), the key structure that connects motor neuron nerves with muscle cells, shows increased defects with ageing. Previous studies in various species have shown that with ageing, type II fast-twitch skeletal muscle fibres show more atrophy and NMJ deterioration than type I slow-twitch fibres. However, how this process is regulated is largely unknown. A better understanding of the mechanisms regulating skeletal muscle fibre-type specific denervation at the NMJ could be critical to identifying novel treatments for sarcopenia...
April 16, 2017: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/28414717/a-ca2-channel-differentially-regulates-clathrin-mediated-and-activity-dependent-bulk-endocytosis
#12
Chi-Kuang Yao, Yu-Tzu Liu, I-Chi Lee, You-Tung Wang, Ping-Yen Wu
Clathrin-mediated endocytosis (CME) and activity-dependent bulk endocytosis (ADBE) are two predominant forms of synaptic vesicle (SV) endocytosis, elicited by moderate and strong stimuli, respectively. They are tightly coupled with exocytosis for sustained neurotransmission. However, the underlying mechanisms are ill defined. We previously reported that the Flower (Fwe) Ca2+ channel present in SVs is incorporated into the periactive zone upon SV fusion, where it triggers CME, thus coupling exocytosis to CME...
April 2017: PLoS Biology
https://www.readbyqxmd.com/read/28414619/how-the-nerves-reached-the-muscle-bernard-katz-stephen-w-kuffler-and-john-c-eccles-certain-implications-of-exile-for-the-development-of-twentieth-century-neurophysiology
#13
Frank W Stahnisch
This article explores the work by Bernard Katz (1911-2003), Stephen W. Kuffler (1913-1980), and John C. Eccles (1903-1997) on the nerve-muscle junction as a milestone in twentieth-century neurophysiology with wider scientific implications. The historical question is approached from two perspectives: (a) an investigation of twentieth-century solutions to a longer physiological dispute and (b) an examination of a new kind of laboratory and academic cooperation. From this vantage point, the work pursued in Sydney by Sir John Carew Eccles' team on the neuromuscular junction is particularly valuable, since it contributed a central functional element to modern physiological understanding regarding the function and structure of the human and animal nervous system...
April 17, 2017: Journal of the History of the Neurosciences
https://www.readbyqxmd.com/read/28408330/muscarinic-cholinoreceptors-m1-m2-m3-and-m4-type-modulate-the-acetylcholine-secretion-in-the-frog-neuromuscular-junction
#14
Andrei N Tsentsevitsky, Irina V Kovyazina, Leniz F Nurullin, Eugeny E Nikolsky
Muscarinic cholinoreceptors regulate the neurosecretion process in vertebrate neuromuscular junctions. The diversity of muscarinic effects on acetylcholine (ACh) secretion may be attributed to the different muscarinic subtypes involved in this process. In the present study, the location of five muscarinic receptor subtypes (M1, M2, M3, M4 and M5) on the motor nerve terminals of frog cutaneous pectoris muscle was shown using specific polyclonal antibodies. The modulatory roles of these receptors were investigated via assessment of the effects of muscarine and specific muscarinic antagonists on the quantal content of endplate currents (EPCs) and the time course of secretion, which was estimated from the distribution of "real" synaptic delays of EPCs recorded in a low Ca(2+)/high Mg(2+) solution...
April 10, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28402693/heparan-sulfate-proteoglycans-regulate-autophagy-in-drosophila
#15
Claire E Reynolds-Peterson, Na Zhao, Jie Xu, Taryn M Serman, Jielin Xu, Scott B Selleck
Heparan sulfate-modified proteoglycans (HSPGs) are important regulators of signaling and molecular recognition at the cell surface and in the extracellular space. Disruption of HSPG core proteins, HS-synthesis, or HS-degradation can have profound effects on growth, patterning, and cell survival. The Drosophila neuromuscular junction provides a tractable model for understanding the activities of HSPGs at a synapse that displays developmental and activity-dependent plasticity. Muscle cell-specific knockdown of HS biosynthesis disrupted the organization of a specialized postsynaptic membrane, the subsynaptic reticulum (SSR), and affected the number and morphology of mitochondria...
April 12, 2017: Autophagy
https://www.readbyqxmd.com/read/28399101/-clinical-and-epidemiological-characteristics-of-hereditary-motor-sensory-neuropathy-1x-caused-by-the-mutation-c-259c-g-p-p87a-in-the-gjb1-gene-of-patients-from-the-republic-of-bashkortostan
#16
E V Saifullina, R V Magzhanov, I M Khidiyatova, E K Khusnutdinova
BACKGROUND: Hereditary motor-sensory neuropathy 1X (НМСН 1X) is the second frequent form of hereditary motor-sensory neuropathies caused by mutations in the GJB1 gene (gap junction B1 type). The authors have established earlier that the с.259C>G (р.P87A) mutation is the most frequent cause of НМСН 1Х (92%) in patients from the Republic of Bashkortostan. AIM: To study in details the territorial ethnic distribution and clinical manifestations of the с...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/28392766/presence-and-absence-of-muscle-contraction-elicited-by-peripheral-nerve-electrical-stimulation-differentially-modulate-primary-motor-cortex-excitability
#17
Ryoki Sasaki, Shinichi Kotan, Masaki Nakagawa, Shota Miyaguchi, Sho Kojima, Kei Saito, Yasuto Inukai, Hideaki Onishi
Modulation of cortical excitability by sensory inputs is a critical component of sensorimotor integration. Sensory afferents, including muscle and joint afferents, to somatosensory cortex (S1) modulate primary motor cortex (M1) excitability, but the effects of muscle and joint afferents specifically activated by muscle contraction are unknown. We compared motor evoked potentials (MEPs) following median nerve stimulation (MNS) above and below the contraction threshold based on the persistence of M-waves. Peripheral nerve electrical stimulation (PES) conditions, including right MNS at the wrist at 110% motor threshold (MT; 110% MNS condition), right MNS at the index finger (sensory digit nerve stimulation [DNS]) with stimulus intensity approximately 110% MNS (DNS condition), and right MNS at the wrist at 90% MT (90% MNS condition) were applied...
2017: Frontiers in Human Neuroscience
https://www.readbyqxmd.com/read/28390424/grmd-cardiac-and-skeletal-muscle-metabolism-gene-profiles-are-distinct
#18
Larry W Markham, Candice L Brinkmeyer-Langford, Jonathan H Soslow, Manisha Gupte, Douglas B Sawyer, Joe N Kornegay, Cristi L Galindo
BACKGROUND: Duchenne muscular dystrophy (DMD) is caused by mutations in the DMD gene, which codes for the dystrophin protein. While progress has been made in defining the molecular basis and pathogenesis of DMD, major gaps remain in understanding mechanisms that contribute to the marked delay in cardiac compared to skeletal muscle dysfunction. METHODS: To address this question, we analyzed cardiac and skeletal muscle tissue microarrays from golden retriever muscular dystrophy (GRMD) dogs, a genetically and clinically homologous model for DMD...
April 8, 2017: BMC Medical Genomics
https://www.readbyqxmd.com/read/28386022/multiple-roles-of-integrin-%C3%AE-3-at-the-neuromuscular-junction
#19
Jacob A Ross, Richard G Webster, Tanguy Lechertier, Louise E Reynolds, Mark Turmaine, Maximilien Bencze, Yalda Jamshidi, Hakan Cetin, Francesco Muntoni, David Beeson, Kairbaan Hodilvala-Dilke, Francesco J Conti
The neuromuscular junction (NMJ) is the synapse between motoneuron and skeletal muscle, and is responsible for eliciting muscle contraction. Neurotransmission at synapses depends on the release of synaptic vesicles at sites called active zones (AZs). Various proteins of the extracellular matrix are crucial for NMJ development; however little is known about the identity and functions of the receptors that mediate their effects. Using genetically modified mice, we find that integrin-α3, an adhesion receptor at the presynaptic membrane, is involved in the localisation of AZ components and efficient synaptic vesicle release...
April 6, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28379367/a-drosophila-model-of-als-reveals-a-partial-loss-of-function-of-causative-human-pfn1-mutants
#20
Chi-Hong Wu, Anthony Giampetruzzi, Helene Tran, Claudia Fallini, Fen-Biao Gao, John E Landers
Mutations in the profilin 1 (PFN1) gene are causative for familial amyotrophic lateral sclerosis (fALS). However, it is still not fully understood how these mutations lead to neurodegeneration. To address this question, we generated a novel Drosophila model expressing human wild-type and ALS-causative PFN1 mutants. We show that at larval neuromuscular junctions (NMJ), motor neuron expression of wild-type human PFN1 increases the number of ghost boutons, active zone density, F-actin content, and the formation of filopodia...
April 3, 2017: Human Molecular Genetics
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