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https://www.readbyqxmd.com/read/28931313/muscle-expression-of-sod1g93a-triggers-the-dismantlement-of-neuromuscular-junction-via-pkc-theta
#1
Gabriella Dobrowolny, Martina Martini, Bianca Maria Scicchitano, Vanina Romanello, Simona Boncompagni, Carmine Nicoletti, Laura Pietrangelo, Simone De Panfilis, Angela Catizone, Marina Bouche, Marco Sandri, Rudiger Rudolf, Feliciano Protasi, Antonio Musaro
Aim Neuromuscular junction (NMJ) represents the morpho-functional interface between muscle and nerve. Several chronic pathologies such as aging and neurodegenerative diseases, including muscular dystrophy and Amyotrophic Lateral Sclerosis (ALS), display altered NMJ and functional denervation. However, the triggers and the molecular mechanisms underlying the dismantlement of NMJ remain unclear. Results Here we provide evidence that perturbation in redox signaling cascades, induced by muscle-specific accumulation of mutant SOD1G93A in transgenic MLC/SOD1G93A mice, is causally linked to morphological alterations of the neuromuscular presynaptic terminals, high turnover rate of Acetylcholine Receptor (AChR), and NMJ dismantlement...
September 20, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28912273/neuroligin-4-regulates-synaptic-growth-via-the-bone-morphogenetic-protein-bmp-signaling-pathway-at-the-drosophila-neuromuscular-junction
#2
Xinwang Zhang, Menglong Rui, Guangmin Gan, Cong Huang, Jukang Yi, Huihui Lv, Wei Xie
The neuroligin (Nlg) family of neural cell adhesion molecules is thought to be required for synapse formation and development, and has been linked to the development of autism spectrum disorders in humans. In Drosophila melanogaster, mutations in the neuroligin 1-3 genes have been reported to induce synapse developmental defects at neuromuscular junctions (NMJs), but the role of neuroligin 4 (dnlg4) in synapse development has not been determined. Here, we report that the Drosophila neuroligin 4 (DNlg4) is different from DNlg1-3 that it presynaptically regulates NMJ synapse development...
September 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28890686/synaptic-activity-and-muscle-contraction-increases-pdk1-and-pkc%C3%AE-i-phosphorylation-in-the-presynaptic-membrane-of-the-neuromuscular-junction
#3
Erica Hurtado, Víctor Cilleros, Laia Just, Anna Simó, Laura Nadal, Marta Tomàs, Neus Garcia, Maria A Lanuza, Josep Tomàs
Conventional protein kinase C βI (cPKCβI) is a conventional protein kinase C (PKC) isoform directly involved in the regulation of neurotransmitter release in the neuromuscular junction (NMJ). It is located exclusively at the nerve terminal and both synaptic activity and muscle contraction modulate its protein levels and phosphorylation. cPKCβI molecular maturation includes a series of phosphorylation steps, the first of which is mediated by phosphoinositide-dependent kinase 1 (PDK1). Here, we sought to localize PDK1 in the NMJ and investigate the hypothesis that synaptic activity and muscle contraction regulate in parallel PDK1 and cPKCβI phosphorylation in the membrane fraction...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28890682/impaired-mitophagy-plays-a-role-in-denervation-of-neuromuscular-junctions-in-als-mice
#4
Robert S Rogers, Sudheer Tungtur, Tomohiro Tanaka, Lisa L Nadeau, Yomna Badawi, Hua Wang, Hong-Min Ni, Wen-Xing Ding, Hiroshi Nishimune
Motor neurons in amyotrophic lateral sclerosis (ALS) patients and animal models show degeneration from the nerve terminal, known as dying-back neuropathy. To investigate the mechanism underlying this neuropathy, we analyzed the neuromuscular junctions (NMJs) and motor neuron cell bodies in SOD1(G93A) mice using electron microscopy. NMJs of SOD1(G93A) mice exhibited significantly higher numbers of autophagosomes and degenerated mitochondria compared to wild-type controls. Mitophagosomes were identified in the NMJ presynaptic terminals of wild-type mice and SOD1(G93A) mice...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28885698/autoimmune-antibodies-to-collagen-xiii-in-myasthenia-gravis-patients
#5
Hongmin Tu, Ritva Pirskanen-Matell, Anne Heikkinen, Tuomo Oikarainen, Juha Risteli, Taina Pihlajaniemi
INTRODUCTION: Myasthenia Gravis (MG) is a neuromuscular junction (NMJ) disorder caused by autoantibodies against NMJ proteins. Collagen XIII is a muscle-derived transmembrane protein required for NMJ maturation. The objective of this study is to explore existence of autoantibodies to collagen XIII in MG patients. METHODS: Seventy MG patient sera and 61 human healthy controls were screened for collagen XIII autoantibodies by enzyme-linked immunosorbent assay (ELISA)...
September 8, 2017: Muscle & Nerve
https://www.readbyqxmd.com/read/28878618/the-non-survival-effects-of-glial-cell-line-derived-neurotrophic-factor-on-neural-cells
#6
REVIEW
Daniel Cortés, Oscar A Carballo-Molina, María José Castellanos-Montiel, Iván Velasco
Glial cell line-derived neurotrophic factor (GDNF) was first characterized as a survival-promoting molecule for dopaminergic neurons (DANs). Afterwards, other cells were also discovered to respond to GDNF not only as a survival factor but also as a protein supporting other cellular functions, such as proliferation, differentiation, maturation, neurite outgrowth and other phenomena that have been less studied than survival and are now more extendedly described here in this review article. During development, GDNF favors the commitment of neural precursors towards dopaminergic, motor, enteric and adrenal neurons; in addition, it enhances the axonal growth of some of these neurons...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28873252/carbonic-anhydrase-inhibitor-acetazolamide-shifts-synaptic-vesicle-recycling-to-a-fast-mode-at-the-mouse-neuromuscular-junction
#7
Nicolas Ivan Bertone, Ayelén Ivana Groisman, Graciela Lujan Mazzone, Raquel Cano, Lucia Tabares, Osvaldo Daniel Uchitel
Acetazolamide (AZ), a molecule frequently used to treat different neurological syndromes, is an inhibitor of the carbonic anhydrase (CA), an enzyme that regulates pH inside and outside cells. We combined fluorescent FM styryl dyes and electrophysiological techniques at ex vivo levator auris longus neuromuscular junctions (NMJs) from mice to investigate the modulation of synaptic transmission and vesicle recycling by AZ. Transmitter release was minimally affected by AZ, as evidenced by evoked and spontaneous end-plate potential measurements...
September 5, 2017: Synapse
https://www.readbyqxmd.com/read/28860114/notum-coordinates-synapse-development-via-extracellular-regulation-of-wnt-wingless-trans-synaptic-signaling
#8
Danielle L Kopke, Sofia C Lima, Cyrille Alexandre, Kendal Broadie
Synaptogenesis requires orchestrated communication between pre- and postsynaptic cells via coordinated trans-synaptic signaling across the extracellular synaptomatrix. The first discovered Wnt signaling ligand Drosophila Wingless (Wg; Wnt-1 in mammals) plays critical roles in synaptic development, regulating synapse architecture as well as functional differentiation. Here, we investigate synaptogenic functions of the secreted extracellular deacylase Notum, which restricts Wg signaling by cleaving an essential palmitoleate moiety...
August 31, 2017: Development
https://www.readbyqxmd.com/read/28846707/kek-6-a-truncated-trk-like-receptor-for-drosophila-neurotrophin-2-regulates-structural-synaptic-plasticity
#9
Suzana Ulian-Benitez, Simon Bishop, Istvan Foldi, Jill Wentzell, Chinenye Okenwa, Manuel G Forero, Bangfu Zhu, Marta Moreira, Mark Phizacklea, Graham McIlroy, Guiyi Li, Nicholas J Gay, Alicia Hidalgo
Neurotrophism, structural plasticity, learning and long-term memory in mammals critically depend on neurotrophins binding Trk receptors to activate tyrosine kinase (TyrK) signaling, but Drosophila lacks full-length Trks, raising the question of how these processes occur in the fly. Paradoxically, truncated Trk isoforms lacking the TyrK predominate in the adult human brain, but whether they have neuronal functions independently of full-length Trks is unknown. Drosophila has TyrK-less Trk-family receptors, encoded by the kekkon (kek) genes, suggesting that evolutionarily conserved functions for this receptor class may exist...
August 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28846617/in-vitro-innervation-as-an-experimental-model-to-study-the-expression-and-functions-of-acetylcholinesterase-and-agrin-in-human-skeletal-muscle
#10
REVIEW
Katarina Mis, Zoran Grubic, Paola Lorenzon, Marina Sciancalepore, Tomaz Mars, Sergej Pirkmajer
Acetylcholinesterase (AChE) and agrin, a heparan-sulfate proteoglycan, reside in the basal lamina of the neuromuscular junction (NMJ) and play key roles in cholinergic transmission and synaptogenesis. Unlike most NMJ components, AChE and agrin are expressed in skeletal muscle and α-motor neurons. AChE and agrin are also expressed in various other types of cells, where they have important alternative functions that are not related to their classical roles in NMJ. In this review, we first focus on co-cultures of embryonic rat spinal cord explants with human skeletal muscle cells as an experimental model to study functional innervation in vitro...
August 27, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28831123/liprin-%C3%AE-1-is-a-novel-component-of-the-murine-neuromuscular-junction-and-is-involved-in-the-organization-of-the-postsynaptic-machinery
#11
Krzysztof M Bernadzki, Marta Gawor, Marcin Pęziński, Paula Mazurek, Paweł Niewiadomski, Maria J Rędowicz, Tomasz J Prószyński
Neuromuscular junctions (NMJs) are specialized synapses that connect motor neurons to skeletal muscle fibers and orchestrate proper signal transmission from the nervous system to muscles. The efficient formation and maintenance of the postsynaptic machinery that contains acetylcholine receptors (AChR) are indispensable for proper NMJ function. Abnormalities in the organization of synaptic components often cause severe neuromuscular disorders, such as muscular dystrophy. The dystrophin-associated glycoprotein complex (DGC) was shown to play an important role in NMJ development...
August 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821658/opposite-synaptic-alterations-at-the-neuromuscular-junction-in-an-als-mouse-model-when-motor-units-matter
#12
Tremblay Elsa, Martineau Éric, Robitaille Richard
Denervation of the neuromuscular junction (NMJ) precedes the loss of motor neurons (MNs) in amyotrophic lateral sclerosis (ALS). ALS is characterized by a motor unit (MU) dependent vulnerability where MNs with fast-fatigable (FF) characteristics are lost first, followed by fast-fatigue resistant (FR) and slow (S) ones. However, changes of NMJ properties as a function of MU types remain debated. We hypothesized that NMJ synaptic functions would be altered precociously in a MU specific manner, prior to structural alterations of the NMJ...
August 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28811140/divergent-effects-of-resistance-training-and-anabolic-steroid-on-the-postsynaptic-region-of-different-skeletal-muscles-of-aged-rats
#13
Walter Krause Neto, Wellington de Assis Silva, Adriano Polican Ciena, Carlos Alberto Anaruma, Eliane Florencio Gama
This study aimed to analyze the effects of resistance training associated with testosterone administration in the neuromuscular junction (NMJ) postsynaptic region of different skeletal muscle types of aged rats. Wistar rats were divided into: SEI - 20-months-old control, SEF - 24-months-old control, T - 20-months-old with testosterone, S - 20-months-old resistance trained and ST - 20-months-old with resistance training associated with testosterone propionate. All groups were submitted to familiarization and maximum load carrying testing (MLCT)...
August 12, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28809841/measuring-neuromuscular-junction-functionality
#14
Emanuele Rizzuto, Simona Pisu, Carmine Nicoletti, Zaccaria Del Prete, Antonio Musarò
Neuromuscular junction (NMJ) functionality plays a pivotal role when studying diseases in which the communication between motor neuron and muscle is impaired, such as aging and amyotrophic lateral sclerosis (ALS). Here we describe an experimental protocol that can be used to measure NMJ functionality by combining two types of electrical stimulation: direct muscle membrane stimulation and the stimulation through the nerve. The comparison of the muscle response to these two different stimulations can help to define, at the functional level, potential alterations in the NMJ that lead to functional decline in muscle...
August 6, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28798955/super-resolution-microscopy-reveals-a-nanoscale-organization-of-acetylcholine-receptors-for-trans-synaptic-alignment-at-neuromuscular-synapses
#15
Amanda L York, James Q Zheng
The neuromuscular junction (NMJ) is a chemical synapse formed between motoneurons and skeletal muscle fibers. The vertebrate NMJ uses acetylcholine (ACh) as the neurotransmitter and features numerous invaginations of the postsynaptic muscle membrane termed junctional folds. ACh receptors (AChRs) are believed to be concentrated on the crest of junctional folds but their spatial organization remains to be fully understood. In this study, we utilized super-resolution microscopy to examine the nanoscale organization of AChRs at NMJ...
July 2017: ENeuro
https://www.readbyqxmd.com/read/28790398/shedding-light-on-alzheimer-s-%C3%AE-amyloidosis-photosensitized-methylene-blue-inhibits-self-assembly-of-%C3%AE-amyloid-peptides-and-disintegrates-their-aggregates
#16
Byung Il Lee, Yoon Seok Suh, You Jung Chung, Kweon Yu, Chan Beum Park
Abnormal aggregation of β-amyloid (Aβ) peptides is a major hallmark of Alzheimer's disease (AD). In spite of numerous attempts to prevent the β-amyloidosis, no effective drugs for treating AD have been developed to date. Among many candidate chemicals, methylene blue (MB) has proved its therapeutic potential for AD in a number of in vitro and in vivo studies; but the result of recent clinical trials performed with MB and its derivative was negative. Here, with the aid of multiple photochemical analyses, we first report that photoexcited MB molecules can block Aβ42 aggregation in vitro...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28780847/-characteristics-of-repetitive-nerve-stimulation-in-53-cases-of-amyotrophic-lateral-sclerosis
#17
W X Liu, Z H Chen, L Ling, Y T Ren, B Sun, F Yang, F Cui, X S Huang
Objective: To investigate the feature of repetitive nerve stimulation (RNS) in patients with amyotrophic lateral sclerosis (ALS) and correlation between RNS and clinical features and electromyography (EMG) findings of the corresponding muscle. Methods: Needle EMG and RNS were performed in 53 patients with ALS, who were recruited into Department of Neurology of Chinese PLA general hospital during April to December in 2016. Decrement of the compond muscle action potential (CMAP) in response to RNS of different nerves and stimulus frequencies was compared...
August 1, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28759703/extracorporeal-shock-wave-treatment-can-selectively-destroy-endplates-in-neuromuscular-junctions
#18
Tomonori Kenmoku, Noriko Nemoto, Nahoko Iwakura, Nobuyasu Ochiai, Kentaro Uchida, Takashi Saisu, Seiji Ohtori, Koichi Nakagawa, Takahisa Sasho, Masashi Takaso
INTRODUCTION: This study assessed the effect of radial extracorporeal shock wave (rESW) exposure on neuromuscular transmission and neuromuscular junction (NMJ) morphology. METHODS: We applied 2,000 rESWs at 0.18 mJ/mm(2) and a frequency of 15 Hz to the right calf of male rats, measured the compound muscle action potential (CMAP) and examined NMJ morphology using electron microscopy. Left calf muscles were used as controls. RESULTS: rESW exposure significantly reduced CMAP amplitude without delayed latency in exposed muscles compared to controls...
July 31, 2017: Muscle & Nerve
https://www.readbyqxmd.com/read/28745645/a-simple-neuronal-mechanical-injury-methodology-to-study-drosophila-motor-neuron-degeneration
#19
Erika B Danella, Lani C Keller
The degeneration of neurons occurs during normal development and in response to injury, stress, and disease. The cellular hallmarks of neuronal degeneration are remarkably similar in humans and invertebrates as are the molecular mechanisms that drive these processes. The fruit fly, Drosophila melanogaster, provides a powerful yet simple genetic model organism to study the cellular complexities of neurodegenerative diseases. In fact, approximately 70% of disease-associated human genes have a Drosophila homolog and a plethora of tools and assays have been described using flies to study human neurodegenerative diseases...
July 19, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28729214/milk-fat-globule-membrane-supplementation-with-voluntary-running-exercise-attenuates-age-related-motor-dysfunction-by-suppressing-neuromuscular-junction-abnormalities-in-mice
#20
Michiko Yano, Yoshihiko Minegishi, Satoshi Sugita, Noriyasu Ota
Age-related loss of skeletal muscle mass and function attenuates physical performance, and maintaining fine muscle innervation is known to play an important role in its prevention. We had previously shown that consumption of milk fat globule membrane (MFGM) with habitual exercise improves the muscle mass and motor function in humans and mice. Improvement of neuromuscular junction (NMJ) was suggested as one of the mechanisms underlying these effects. In this study, we evaluated the effect of MFGM intake combined with voluntary running (MFGM-VR) on morphological changes of NMJ and motor function in aging mice...
July 18, 2017: Experimental Gerontology
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