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neuromuscular junction physiology

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https://www.readbyqxmd.com/read/29782610/castration-induces-satellite-cell-activation-that-contributes-to-skeletal-muscle-maintenance
#1
Alanna Klose, Wenxuan Liu, Nicole D Paris, Sophie Forman, John J Krolewski, Kent L Nastiuk, Joe V Chakkalakal
Background: Sarcopenia, the age-related loss of skeletal muscle, is a side effect of androgen deprivation therapy (ADT) for prostate cancer patients. Resident stem cells of skeletal muscle, satellite cells (SCs), are an essential source of progenitors for the growth and regeneration of skeletal muscle. Decreased androgen signaling and deficits in the number and function of SCs are features of aging. Although androgen signaling is known to regulate skeletal muscle, the cellular basis for ADT-induced exacerbation of sarcopenia is unknown...
2018: JCSM rapid communications
https://www.readbyqxmd.com/read/29779594/disorders-of-the-diaphragm
#2
REVIEW
F Dennis McCool, Kamran Manzoor, Taro Minami
Pathologic processes that involve the central nervous system, phrenic nerve, neuromuscular junction, and skeletal muscle can impair diaphragm function. When these processes are of sufficient severity to cause diaphragm dysfunction, respiratory failure may be a consequence. This article reviews basic diaphragm anatomy and physiology and then discusses diagnostic and therapeutic approaches to disorders that result in unilateral or bilateral diaphragm dysfunction. This discussion provides a context in which disorders of the diaphragm and their implications on respiratory function can be better appreciated...
June 2018: Clinics in Chest Medicine
https://www.readbyqxmd.com/read/29739270/bioinspired-3d-human-neuromuscular-junction-development-in-suspended-hydrogel-arrays
#3
Thomas Dixon, Eliad Cohen, Dana Meredith Cairns, Maria Rodriguez, Juanita Mathews, Rod Jose, David L Kaplan
The physical connection between motoneurons and skeletal muscle targets is responsible for the creation of neuromuscular junctions (NMJs), which allow electrical signals to be translated to mechanical work. NMJ pathology contributes to the spectrum of neuromuscular, motoneuron, and dystrophic disease. Improving in vitro tools that allow for recapitulation of the physiology of the neuromuscular connection will enable researchers to better understand the development and maturation of NMJs, and will help to decipher mechanisms leading to NMJ degeneration...
May 9, 2018: Tissue Engineering. Part C, Methods
https://www.readbyqxmd.com/read/29693600/exploiting-botulinum-neurotoxins-for-the-study-of-brain-physiology-and-pathology
#4
REVIEW
Matteo Caleo, Laura Restani
Botulinum neurotoxins are metalloproteases that specifically cleave N -ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins in synaptic terminals, resulting in a potent inhibition of vesicle fusion and transmitter release. The family comprises different serotypes (BoNT/A to BoNT/G). The natural target of these toxins is represented by the neuromuscular junction, where BoNTs block acetylcholine release. In this review, we describe the actions of botulinum toxins after direct delivery to the central nervous system (CNS), where BoNTs block exocytosis of several transmitters, with near-complete silencing of neural networks...
April 25, 2018: Toxins
https://www.readbyqxmd.com/read/29655450/nature-and-action-of-antibodies-in-myasthenia-gravis
#5
REVIEW
Robert L Ruff, Robert P Lisak
This article discusses antibodies associated with immune-mediated myasthenia gravis and the pathologic action of these antibodies at the neuromuscular junctions of skeletal muscle. To explain how these antibodies act, we consider the physiology of neuromuscular transmission with emphasis on 4 features: the structure of the neuromuscular junction; the roles of postsynaptic acetylcholine receptors and voltage-gated Na+ channels and in converting the chemical signal from the nerve terminal into a propagated action potential on the muscle fiber that triggers muscle contraction; the safety factor for neuromuscular transmission; and how the safety factor is reduced in different forms of autoimmune myasthenia gravis...
May 2018: Neurologic Clinics
https://www.readbyqxmd.com/read/29609424/synergistic-activities-of-abdominal-muscles-are-required-for-efficient-micturition-in-anesthetized-female-mice
#6
Chuan Zhang, Yingchun Zhang, Yolanda Cruz, Timothy B Boone, Alvaro Munoz
PURPOSE: To characterize the electromyographic activity of abdominal striated muscles during micturition in urethane-anesthetized female mice, and to quantitatively evaluate the contribution of abdominal responses to efficient voiding. METHODS: Cystometric and multichannel electromyographic recordings were integrated to enable a comprehensive evaluation during micturition in urethane-anesthetized female mice. Four major abdominal muscle domains were evaluated: the external oblique, internal oblique, and superior and inferior rectus abdominis...
March 2018: International Neurourology Journal
https://www.readbyqxmd.com/read/29580378/hypoexcitability-precedes-denervation-in-the-large-fast-contracting-motor-units-in-two-unrelated-mouse-models-of-als
#7
Maria de Lourdes Martinez-Silva, Rebecca D Imhoff-Manuel, Aarti Sharma, C J Heckman, Neil A Shneider, Francesco Roselli, Daniel Zytnicki, Marin Manuel
Hyperexcitability has been suggested to contribute to motoneuron degeneration in amyotrophic lateral sclerosis (ALS). If this is so, and given that the physiological type of a motor unit determines the relative susceptibility of its motoneuron in ALS, then one would expect the most vulnerable motoneurons to display the strongest hyperexcitability prior to their degeneration, whereas the less vulnerable should display a moderate hyperexcitability, if any. We tested this hypothesis in vivo in two unrelated ALS mouse models by correlating the electrical properties of motoneurons with their physiological types, identified based on their motor unit contractile properties...
March 27, 2018: ELife
https://www.readbyqxmd.com/read/29572431/a-gain-of-function-mutation-in-the-%C3%AE-9-nicotinic-acetylcholine-receptor-alters-medial-olivocochlear-efferent-short-term-synaptic-plasticity
#8
Carolina Wedemeyer, Lucas G Vattino, Marcelo J Moglie, Jimena Ballestero, Stéphane F Maison, Mariano N Di Guilmi, Julian Taranda, M Charles Liberman, Paul A Fuchs, Eleonora Katz, Ana Belén Elgoyhen
Gain control of the auditory system operates at multiple levels. Cholinergic medial olivocochlear (MOC) fibers originate in the brainstem and make synaptic contacts at the base of the outer hair cells (OHCs), the final targets of several feedback loops from the periphery and higher processing centers. Efferent activation inhibits OHC active amplification within the mammalian cochlea, through the activation of a calcium permeable α9α10 ionotropic cholinergic nicotinic receptor (nAChR), functionally coupled to calcium activated SK2 potassium channels...
March 23, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29572064/the-role-of-ampk-in-neuromuscular-biology-and-disease
#9
REVIEW
Athan G Dial, Sean Y Ng, Alexander Manta, Vladimir Ljubicic
AMP-activated protein kinase (AMPK) is a primary regulator of cellular metabolism. Recent studies have revealed that AMPK also mediates the maintenance and plasticity of α-motoneurons, the neuromuscular junction, and skeletal muscle. Furthermore, AMPK stimulation by either genetic, pharmacological, or physiological approaches elicits beneficial phenotypic remodeling in neuromuscular disorders (NMDs). Here, we review the role of AMPK as a governor of neuromuscular biology, and present evidence for AMPK as an effective molecular target for therapeutic pursuit in the context of the most prevalent NMDs, including Duchenne muscular dystrophy, spinal muscular atrophy, and myotonic dystrophy type 1...
May 2018: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/29549349/cannabinoid-induced-increase-of-quantal-size-and-enhanced-neuromuscular-transmission
#10
Marco Morsch, Dario A Protti, Delfine Cheng, Filip Braet, Roger S Chung, Stephen W Reddel, William D Phillips
Cannabinoids exert dynamic control over many physiological processes including memory formation, cognition and pain perception. In the central nervous system endocannabinoids mediate negative feedback of quantal transmitter release following postsynaptic depolarization. The influence of cannabinoids in the peripheral nervous system is less clear and might have broad implications for the therapeutic application of cannabinoids. We report a novel cannabinoid effect upon the mouse neuromuscular synapse: acutely increasing synaptic vesicle volume and raising the quantal amplitudes...
March 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29547745/stem-cell-derived-phenotypic-human-neuromuscular-junction-model-for-dose-response-evaluation-of-therapeutics
#11
Navaneetha Santhanam, Lee Kumanchik, Xiufang Guo, Frank Sommerhage, Yunqing Cai, Max Jackson, Candace Martin, George Saad, Christopher W McAleer, Ying Wang, Andrea Lavado, Christopher J Long, James J Hickman
There are currently no functional neuromuscular junction (hNMJ) systems composed of human cells that could be used for drug evaluations or toxicity testing in vitro. These systems are needed to evaluate NMJs for diseases such as amyotrophic lateral sclerosis, spinal muscular atrophy or other neurodegenerative diseases or injury states. There are certainly no model systems, animal or human, that allows for isolated treatment of motoneurons or muscle capable of generating dose response curves to evaluate pharmacological activity of these highly specialized functional units...
June 2018: Biomaterials
https://www.readbyqxmd.com/read/29499182/glucuronylated-core-1-glycans-are-required-for-precise-localization-of-neuromuscular-junctions-and-normal-formation-of-basement-membranes-on-drosophila-muscles
#12
Kazuyoshi Itoh, Yoshihiro Akimoto, Shu Kondo, Tomomi Ichimiya, Kazuhiro Aoki, Michael Tiemeyer, Shoko Nishihara
T antigen (Galβ1-3GalNAcα1-Ser/Thr) is an evolutionary-conserved mucin-type core 1 glycan structure in animals synthesized by core 1 β1,3-galactosyltransferase 1 (C1GalT1). Previous studies showed that T antigen produced by Drosophila C1GalT1 (dC1GalT1) was expressed in various tissues and dC1GalT1 loss in larvae led to various defects, including decreased number of circulating hemocytes, hyper-differentiation of hematopoietic stem cells in lymph glands, malformation of the central nervous system, mislocalization of neuromuscular junction (NMJ) boutons, and ultrastructural abnormalities in NMJs and muscle cells...
April 15, 2018: Developmental Biology
https://www.readbyqxmd.com/read/29475025/protein-anchoring-therapy-to-target-extracellular-matrix-proteins-to-their-physiological-destinations
#13
REVIEW
Mikako Ito, Kinji Ohno
Endplate acetylcholinesterase (AChE) deficiency is a form of congenital myasthenic syndrome (CMS) caused by mutations in COLQ, which encodes collagen Q (ColQ). ColQ is an extracellular matrix (ECM) protein that anchors AChE to the synaptic basal lamina. Biglycan, encoded by BGN, is another ECM protein that binds to the dystrophin-associated protein complex (DAPC) on skeletal muscle, which links the actin cytoskeleton and ECM proteins to stabilize the sarcolemma during repeated muscle contractions. Upregulation of biglycan stabilizes the DPAC...
February 20, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29464198/unraveling-synaptic-gcamp-signals-differential-excitability-and-clearance-mechanisms-underlying-distinct-ca-2-dynamics-in-tonic-and-phasic-excitatory-and-aminergic-modulatory-motor-terminals-in-drosophila
#14
Xiaomin Xing, Chun-Fang Wu
GCaMP is an optogenetic Ca2+ sensor widely used for monitoring neuronal activities but the precise physiological implications of GCaMP signals remain to be further delineated among functionally distinct synapses. The Drosophila neuromuscular junction (NMJ), a powerful genetic system for studying synaptic function and plasticity, consists of tonic and phasic glutamatergic and modulatory aminergic motor terminals of distinct properties. We report a first simultaneous imaging and electric recording study to directly contrast the frequency characteristics of GCaMP signals of the three synapses for physiological implications...
January 2018: ENeuro
https://www.readbyqxmd.com/read/29411505/transcriptomics-of-aged-drosophila-motor-neurons-reveals-a-matrix-metalloproteinase-that-impairs-motor-function
#15
Jorge Azpurua, Rebekah E Mahoney, Benjamin A Eaton
The neuromuscular junction (NMJ) is responsible for transforming nervous system signals into motor behavior and locomotion. In the fruit fly Drosophila melanogaster, an age-dependent decline in motor function occurs, analogous to the decline experienced in mice, humans, and other mammals. The molecular and cellular underpinnings of this decline are still poorly understood. By specifically profiling the transcriptome of Drosophila motor neurons across age using custom microarrays, we found that the expression of the matrix metalloproteinase 1 (dMMP1) gene reproducibly increased in motor neurons in an age-dependent manner...
April 2018: Aging Cell
https://www.readbyqxmd.com/read/29405353/congenital-myasthenic-syndromes-with-acetylcholinesterase-deficiency-the-pathophysiological-mechanisms
#16
REVIEW
Claire Legay
The neuromuscular junction (NMJ) is a cholinergic synapse in vertebrates. This synapse connects motoneurons to muscles and is responsible for muscle contraction, a physiological process that is essential for survival. A key factor for the normal functioning of this synapse is the regulation of acetylcholine (ACh) levels in the synaptic cleft. This is ensured by acetylcholinesterase (AChE), which degrades ACh. A number of mutations in synaptic genes expressed in motoneurons or muscle cells have been identified and are causative for a class of neuromuscular diseases called congenital myasthenic syndromes (CMSs)...
February 2018: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29388464/unraveling-the-role-of-motoneuron-autophagy-in-als
#17
Vicente Valenzuela, Melissa Nassif, Claudio Hetz
In recent years, the role of autophagy in the pathogenesis of most neurodegenerative diseases has transitioned into a limbo of protective or detrimental effects. Genetic evidence indicates that mutations in autophagy-regulatory genes can result in the occurrence of amyotrophic lateral sclerosis (ALS), suggesting a physiological role of the pathway to motoneuron function. However, experimental manipulation of autophagy in ALS models led to conflicting results depending on the intervention strategy and the disease model used...
March 13, 2018: Autophagy
https://www.readbyqxmd.com/read/29371678/inwardly-rectifying-potassium-kir-channels-represent-a-critical-ion-conductance-pathway-in-the-nervous-systems-of-insects
#18
Rui Chen, Daniel R Swale
A complete understanding of the physiological pathways critical for proper function of the insect nervous system is still lacking. The recent development of potent and selective small-molecule modulators of insect inward rectifier potassium (Kir) channels has enabled the interrogation of the physiological role and toxicological potential of Kir channels within various insect tissue systems. Therefore, we aimed to highlight the physiological and functional role of neural Kir channels the central nervous system, muscular system, and neuromuscular system through pharmacological and genetic manipulations...
January 25, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29357501/effects-of-aging-and-parkinson-s-disease-on-motor-unit-remodeling-influence-of-resistance-exercise-training
#19
Neil A Kelly, Kelley G Hammond, C Scott Bickel, Samuel T Windham, S Craig Tuggle, Marcas M Bamman
Aging muscle atrophy is in part a neurodegenerative process revealed by denervation/reinnervation events leading to motor unit remodeling (i.e., myofiber type grouping). However, this process and its physiological relevance are poorly understood, as is the wide-ranging heterogeneity among aging humans. Here, we attempted to address 1) the relation between myofiber type grouping and molecular regulators of neuromuscular junction (NMJ) stability; 2) the impact of motor unit remodeling on recruitment during submaximal contractions; 3) the prevalence and impact of motor unit remodeling in Parkinson's disease (PD), an age-related neurodegenerative disease; and 4) the influence of resistance exercise training (RT) on regulators of motor unit remodeling...
April 1, 2018: Journal of Applied Physiology
https://www.readbyqxmd.com/read/29357458/transmitter-release-site-organization-can-predict-synaptic-function-at-the-neuromuscular-junction
#20
Rozita Laghaei, Jun Ma, Tyler B Tarr, Anne E Homan, Lauren Kelly, Megha S Tilvawala, Blake S Vuocolo, Harini P Rajasekaran, Stephen D Meriney, Markus Dittrich
We have investigated the impact of transmitter release site (active zone; AZ) structure on synaptic function by physically rearranging the individual AZ elements in a previously published frog neuromuscular junction (NMJ) AZ model into the organization observed in a mouse NMJ AZ. We have used this strategy, purposefully without changing the properties of AZ elements between frog and mouse models (even though there are undoubtedly differences between frog and mouse AZ elements in vivo), to directly test how structure influences function at the level of an AZ...
April 1, 2018: Journal of Neurophysiology
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