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https://www.readbyqxmd.com/read/29743034/glial-cell-line-derived-neurotrophic-factor-gdnf-attenuates-the-peripheral-neuromuscular-dysfunction-without-inhibiting-the-activation-of-spinal-microglia-monocyte
#1
Fei Xie, Fan Zhang, Su Min, Jingyuan Chen, Jun Yang, Xin Wang
BACKGROUND: Peripheral neuromuscular dysfunctions were found in elderly individuals, and spinal microglia/monocyte plays an important role on this process. This study aims to test whether the glial cell line-derived neurotrophic factor (GDNF) could attenuate age-related neuromuscular dysfunction by inhibiting the activation of spinal microglia/monocyte. METHODS: Male Sprague-Dawley rats were divided into an adult group and an aged group. The aged rats were intrathecally injected with normal saline (NS) and GDNF...
May 9, 2018: BMC Geriatrics
https://www.readbyqxmd.com/read/29733889/adenosine-promotes-endplate-nachr-channel-activity-in-adult-mouse-skeletal-muscle-fibres-via-low-affinity-p1-receptors
#2
Annalisa Bernareggi, Elisa Ren, Arthur Giniatullin, Elisa Luin, Marina Sciancalepore, Rashid Giniatullin, Paola Lorenzon
Adenosine is a powerful modulator of skeletal neuromuscular transmission, operating via inhibitory or facilitatory purinergic-type P1 receptors. To date, studies have been focused mainly on the effect of adenosine on presynaptic P1 receptors controlling transmitter release. In this study, using two-microelectrode voltage clamp and single channel patch-clamp recording techniques, we have explored potential postsynaptic targets of adenosine and their modulatory effect on nicotinic acetylcholine receptor (nAChR)-mediated synaptic responses in adult mouse skeletal muscle fibres in vitro...
May 4, 2018: Neuroscience
https://www.readbyqxmd.com/read/29719042/early-endplate-remodeling-and-skeletal-muscle-signaling-events-following-rat-hindlimb-suspension
#3
Alexander V Chibalin, Boubacar Benziane, Guzalija F Zakyrjanova, Violetta V Kravtsova, Igor I Krivoi
Motor endplates naturally undergo continual morphological changes that are altered in response to changes in neuromuscular activity. This study examines the consequences of acute (6-12 hr) disuse following hindlimb suspension on rat soleus muscle endplate structural stability. We identify early changes in several key signaling events including markers of protein kinase activation, AMPK phosphorylation and autophagy markers which may play a role in endplate remodeling. Acute disuse does not change endplate fragmentation, however, it decreases both the individual fragments and the total endplate area...
May 2, 2018: Journal of Cellular Physiology
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
#4
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/29518096/myasthenia-gravis-seronegative-for-acetylcholine-receptor-antibodies-in-south-korea-autoantibody-profiles-and-clinical-features
#5
Kee Hong Park, Patrick Waters, Mark Woodhall, Bethan Lang, Thomas Smith, Jung-Joon Sung, Kwang-Kuk Kim, Young-Min Lim, Jee-Eun Kim, Byung-Jo Kim, Jin-Sung Park, Jeong-Geon Lim, Dae-Seong Kim, Ohyun Kwon, Eun Hee Sohn, Jong Seok Bae, Byung-Nam Yoon, Nam-Hee Kim, Suk-Won Ahn, Jeeyoung Oh, Hyung Jun Park, Kyong Jin Shin, Yoon-Ho Hong
Acquired myasthenia gravis (MG) is a prototype autoimmune disease of the neuromuscular junction, caused in most patients by autoantibodies to the muscle nicotinic acetylcholine receptor (AChR). There seem to be ethnic and regional differences in the frequency and clinical features of MG seronegative for the AChR antibody. This study aimed to describe the autoantibody profiles and clinical features of Korean patients with generalized MG seronegative for the AChR antibody. A total of 62 patients with a high index of clinical suspicion of seronegative generalized MG were identified from 18 centers, and we examined their sera for antibodies to clustered AChR, muscle-specific tyrosine kinase (MuSK), and low-density lipoprotein receptor-related protein 4 (LRP4) by cell-based assays (CBA) and to MuSK by radioimmunoprecipitation assay (RIPA)...
2018: PloS One
https://www.readbyqxmd.com/read/29326174/muscle-nicotinic-acetylcholine-receptors-may-mediate-trans-synaptic-signaling-at-the-mouse-neuromuscular-junction
#6
Xueyong Wang, J Michael McIntosh, Mark M Rich
Block of neurotransmitter receptors at the neuromuscular junction (NMJ) has been shown to trigger upregulation of the number of synaptic vesicles released (quantal content, QC), a response termed homeostatic synaptic plasticity. The mechanism underlying this plasticity is not known. Here, we used selective toxins to demonstrate that block of α1-containing nicotinic acetylcholine receptors (nAChRs) at the NMJ of male and female mice triggers the upregulation of QC. Reduction of current flow through nAChRs, induced by drugs with antagonist activity, demonstrated that reduction in synaptic current per se does not trigger upregulation of QC...
February 14, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29236668/-claude-bernard-and-nicotinic-receptors-from-the-neuromuscular-junction-to-tobacco-weaning
#7
Laurent Monassier
Claude Bernard (1813-1878) was fascinated by the pharmacological mechanisms of poisons. In particular, using a huge amount of ingenious and robust experiments, he demonstrated the peripheral toxic action of the natural compound curare. His work generated controversies in a period where scientific methodology and technical development followed the progression of concepts and ideas. From his intense debates with Albert Vulpian emerged the location of curare's toxicity at the neuromuscular junction. These two fascinating scientists could not imagine how important were these discoveries which allowed John Langley to propose the concept of receptor early in the 20th century...
2017: Biologie Aujourd'hui
https://www.readbyqxmd.com/read/29217407/can-we-predict-intermediate-syndrome-a-review
#8
REVIEW
Chanika Alahakoon, Tharaka Lagath Dassanayake, Indika Bandara Gawarammana, Vajira Senaka Weerasinghe
INTRODUCTION: Ingestion of organophosphorus insecticides (OPI) is a common method of deliberate self harm in the developing world. Deaths mainly follow as a result of the respiratory failure associated with both cholinergic crisis and the intermediate syndrome. Even though death can be prevented by early mechanical ventilation of these patients, limited studies are available regarding the prediction of intermediate syndrome and subsequent respiratory failure. OBJECTIVE: To systematically review articles that are published with regard to possible prediction of intermediate syndrome using clinical, biochemical and electrophysiological parameters...
December 5, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/29184265/long-term-low-intensity-endurance-exercise-along-with-blood-flow-restriction-improves-muscle-mass-and-neuromuscular-junction-compartments-in-old-rats
#9
Mohammad-Ali Bahreini Pour, Siyavash Joukar, Fariborz Hovanloo, Hamid Najafipour
Background: During the aging process, muscle atrophy and neuromuscular junction remodeling are inevitable. The present study aimed to clarify whether low-intensity aerobic exercise along with limb blood-flow restriction (BFR) could improve aging-induced muscle atrophy and nicotinic acetylcholine receptors (nAChRs) at the neuromuscular junction. Methods: Forty-eight male Wistar rats, aged 23-24 months, were randomly divided into control, sham (Sh: subjected to surgery without BFR), BFR (subjected to BFR), exercise (Ex: subjected to 10 weeks of low-intensity exercise), Sh+Ex, and BFR+Ex groups...
November 2017: Iranian Journal of Medical Sciences
https://www.readbyqxmd.com/read/29156739/electroacupuncture-alleviates-neuromuscular-dysfunction-in-an-experimental-rat-model-of-immobilization
#10
Jun Yang, Su Min, Fei Xie, Jingyuan Chen, Xuechao Hao, Li Ren
Immobilization-related skeletal muscle atrophy is a major concern to patients in Intensive Care Units and it has a profound effect on the quality of life. However, the underlying molecular events for the therapeutic effect of electroacupuncture to treat muscle atrophy have not been fully elucidated. Here we developed an immobilization mouse model and tested the hypothesis that skeletal muscle weakness may be caused by the increased expression of γ and α7 nicotinic acetylcholine receptors (nAChRs) on muscle cell membranes, while electroacupuncture could decrease the expression of γ and α7 nicotinic acetylcholine receptors...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29046769/factors-that-affect-the-onset-of-action-of-non-depolarizing-neuromuscular-blocking-agents
#11
REVIEW
Yong Byum Kim, Tae-Yun Sung, Hong Seuk Yang
Neuromuscular blockade plays an important role in the safe management of patient airways, surgical field improvement, and respiratory care. Rapid-sequence induction of anesthesia is indispensable to emergency surgery and obstetric anesthesia, and its purpose is to obtain a stable airway, adequate depth of anesthesia, and appropriate respiration within a short period of time without causing irritation or damage to the patient. There has been a continued search for new neuromuscular blocking drugs (NMBDs) with a rapid onset of action...
October 2017: Korean Journal of Anesthesiology
https://www.readbyqxmd.com/read/29040265/analysis-of-peripheral-b-cells-and-autoantibodies-against-the-anti-nicotinic-acetylcholine-receptor-derived-from-patients-with-myasthenia-gravis-using-single-cell-manipulation-tools
#12
Tomohiro Makino, Ryuichi Nakamura, Maki Terakawa, Satoshi Muneoka, Kazuhiro Nagahira, Yuriko Nagane, Jyoji Yamate, Masakatsu Motomura, Kimiaki Utsugisawa
The majority of patients with myasthenia gravis (MG), an organ-specific autoimmune disease, harbor autoantibodies that attack the nicotinic acetylcholine receptor (nAChR-Abs) at the neuromuscular junction of skeletal muscles, resulting in muscle weakness. Single cell manipulation technologies coupled with genetic engineering are very powerful tools to examine T cell and B cell repertoires and the dynamics of adaptive immunity. These tools have been utilized to develop mAbs in parallel with hybridomas, phage display technologies and B-cell immortalization...
2017: PloS One
https://www.readbyqxmd.com/read/29036836/a-panel-of-slow-channel-syndrome-mice-reveals-a-unique-locomotor-behavioral-signature
#13
José G Grajales-Reyes, Aurian García-González, José C María-Ríos, Gary E Grajales-Reyes, Manuel Delgado-Vélez, Carlos A Báez-Pagán, Orestes Quesada, Christopher M Gómez, José A Lasalde-Dominicci
Muscle nicotinic acetylcholine receptor (nAChR) mutations can lead to altered channel kinetics and neuromuscular junction degeneration, a neurodegenerative disorder collectively known as slow-channel syndrome (SCS). A multivariate analysis using running wheels was used to generate activity profiles for a variety of SCS models, uncovering unique locomotor patterns for the different nAChR mutants. Particularly, the αL251T and ɛL269F mutations exhibit decreased event distance, duration, and velocity over a period of 24 hours...
2017: Journal of Neuromuscular Diseases
https://www.readbyqxmd.com/read/28939337/natural-polymeric-3-alkylpyridinium-salt-affects-vertebrate-skeletal-muscle-contractility-by-preferentially-blocking-neuromuscular-transmission
#14
Monika Cecilija Žužek, Marjana Grandič, Evelyne Benoit, Robert Frangež
The effects of natural polymeric alkylpyridinium salt (nPoly-3-APS), a potent acetylcholinesterase inhibitor isolated from the marine sponge Reniera sarai, were studied on isolated mouse phrenic nerve-hemidiaphragm muscle preparations using electrophysiological approaches. nPoly-3-APS inhibited nerve-evoked isometric muscle twitch and tetanic contraction in a concentration-dependent manner (IC50=29.4μM and 18.5μM, respectively) and produced a 30-44% decrease of directly muscle-elicited twitch and tetanus amplitudes at 54...
November 5, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28933591/suppression-of-chrn-endocytosis-by-carbonic-anhydrase-car3-in-the-pathogenesis-of-myasthenia-gravis
#15
Ailian Du, Shiqian Huang, Xiaonan Zhao, Kuan Feng, Shuangyan Zhang, Jiefang Huang, Xiang Miao, Fulvio Baggi, Rennolds S Ostrom, Yanyun Zhang, Xiangjun Chen, Congfeng Xu
Myasthenia gravis is an autoimmune disorder of the neuromuscular junction manifested as fatigable muscle weakness, which is typically caused by pathogenic autoantibodies against postsynaptic CHRN/AChR (cholinergic receptor nicotinic) in the endplate of skeletal muscle. Our previous studies have identified CA3 (carbonic anhydrase 3) as a specific protein insufficient in skeletal muscle from myasthenia gravis patients. In this study, we investigated the underlying mechanism of how CA3 insufficiency might contribute to myasthenia gravis...
2017: Autophagy
https://www.readbyqxmd.com/read/28878016/enantiomeric-barbiturates-bind-distinct-inter-and-intrasubunit-binding-sites-in-a-nicotinic-acetylcholine-receptor-nachr
#16
Zhiyi Yu, Jonathan B Cohen
Nicotinic acetylcholine receptors (nAChRs) and γ-aminobutyric acid type A receptors (GABAA Rs) are members of the pentameric ligand-gated ion channel superfamily. Drugs acting as positive allosteric modulators of muscle-type α2 βγδ nAChRs, of use in treatment of neuromuscular disorders, have been hard to identify. However, identification of nAChR allosteric modulator binding sites has been facilitated by using drugs developed as photoreactive GABAA R modulators. Recently, R- 1-methyl-5-allyl-5-( m -trifluoromethyl-diazirinylphenyl) barbituric acid ( R-m TFD-MPAB), an anesthetic and GABAA R potentiator, has been shown to inhibit Torpedo α2 βγδ nAChRs, binding in the ion channel and to a γ+ -α- subunit interface site similar to its GABAA R intersubunit binding site...
October 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28867438/neuromuscular-paralysis-by-the-basic-phospholipase-a-2-subunit-of-crotoxin-from-crotalus-durissus-terrificus-snake-venom-needs-its-acid-chaperone-to-concurrently-inhibit-acetylcholine-release-and-produce-muscle-blockage
#17
Walter L G Cavalcante, José B Noronha-Matos, Maria A Timóteo, Marcos R M Fontes, Márcia Gallacci, Paulo Correia-de-Sá
BACKGROUND AND PURPOSE: Crotoxin (CTX), a heterodimeric phospholipase A2 (PLA2 ) neurotoxin from Crotalus durissus terrificus snake venom, promotes irreversible blockade of neuromuscular transmission. Indirect electrophysiological evidence suggests that CTX exerts a primary inhibitory action on transmitter exocytosis, yet contribution of a postsynaptic action of the toxin resulting from nicotinic receptor desensitization cannot be excluded. Here, we examined the blocking effect of CTX on nerve-evoked transmitter release measured directly using radioisotope neurochemistry and video microscopy with the FM4-64 fluorescent dye...
November 1, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28777299/ultrafast-and-slow-cholinergic-transmission-different-involvement-of-acetylcholinesterase-molecular-forms
#18
REVIEW
Yves Dunant, Victor Gisiger
Acetylcholine (ACh), an ubiquitous mediator substance broadly expressed in nature, acts as neurotransmitter in cholinergic synapses, generating specific communications with different time-courses. (1) Ultrafast transmission. Vertebrate neuromuscular junctions (NMJs) and nerve-electroplaque junctions (NEJs) are the fastest cholinergic synapses; able to transmit brief impulses (1-4 ms) at high frequencies. The collagen-tailed A12 acetylcholinesterase is concentrated in the synaptic cleft of NMJs and NEJs, were it curtails the postsynaptic response by ultrafast ACh hydrolysis...
August 4, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28762314/insights-into-nicotinic-receptor-signaling-in-nicotine-addiction-implications-for-prevention-and-treatment
#19
Wuyi Liu, Ming D Li
Nicotinic acetylcholine receptors (nAChRs) belong to the Cys-loop ligand-gated ion-channel (LGIC) superfamily, which also includes the GABA, glycine, and serotonin receptors. Many nAChR subunits have been identified and shown to be involved in signal transduction on binding to them of either the neurotransmitter acetylcholine or exogenous ligands such as nicotine. The nAChRs are pentameric assemblies of homologous subunits surrounding a central pore that gates cation flux, and they are expressed at neuromuscular junctions throughout the nervous system...
August 1, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28721012/comparison-of-neurotoxic-potency-between-a-novel-chinbotulinumtoxina-with-onabotulinumtoxina-incobotulinumtoxina-and-lanbotulinumtoxina-in-rats
#20
Ya Feng, Wuchao Liu, Lizhen Pan, Cong Jiang, Chengxi Zhang, Yuxuan Lu, Zhiyu Nie, Lingjing Jin
Four botulinumtoxin type A (BoNT/A) products, onabotulinumtoxinA (A/Ona), incobotulinumtoxinA (A/Inco), lanbotulinumtoxinA (A/Lan) and chinbotulinumtoxinA (A/Chin), are applied in the present study, among which A/Chin is newly produced. We aimed to compare the neurotoxic potency of these toxins by the gauge of muscle strength reduction. Furthermore, potential molecular and cellular mechanisms were also explored. According to our data, muscle strengths in the four toxin groups were all significantly decreased after injection for 1 week...
2017: Drug Design, Development and Therapy
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