keyword
https://read.qxmd.com/read/37458380/nerve-transfer-for-restoration-of-lower-motor-neuron-lesioned-bladder-urethral-and-anal-sphincter-function-in-a-dog-model-nicotinic-receptor-characterization
#21
JOURNAL ARTICLE
Nagat Frara, Mary F Barbe, Dania Giaddui, Danielle S Porreca, Alan S Braverman, Ekta Tiwari, Attia Ahmad, Justin M Brown, Benjamin R Johnston, Stanley F Bazarek, Michael R Ruggieri
Very little is known about the physiological role of nicotinic receptors in canine bladders, although functional nicotinic receptors have been reported in bladders of many species. Utilizing in vitro methods, we evaluated nicotinic receptors mediating bladder function in dogs: Control (9 female and 11 male normal controls, 5 sham-operated), Decentralized (9 females, decentralized 6-21 mo), and obturator-to-pelvic nerve transfer reinnervated (ObNT-Reinn; 9 females; decentralized 9-13 mo, then reinnervated with 8-12 mo recovery)...
July 17, 2023: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://read.qxmd.com/read/37367681/synthesis-and-biological-activity-of-novel-%C3%AE-conotoxins-derived-from-endemic-polynesian-cone-snails
#22
JOURNAL ARTICLE
Yazid Mohamed Souf, Gonxhe Lokaj, Veeresh Kuruva, Yakop Saed, Delphine Raviglione, Ashraf Brik, Annette Nicke, Nicolas Inguimbert, Sébastien Dutertre
α-Conotoxins are well-known probes for the characterization of the various subtypes of nicotinic acetylcholine receptors (nAChRs). Identifying new α-conotoxins with different pharmacological profiles can provide further insights into the physiological or pathological roles of the numerous nAChR isoforms found at the neuromuscular junction, the central and peripheral nervous systems, and other cells such as immune cells. This study focuses on the synthesis and characterization of two novel α-conotoxins obtained from two species endemic to the Marquesas Islands, namely Conus gauguini and Conus adamsonii ...
June 9, 2023: Marine Drugs
https://read.qxmd.com/read/37334046/-e-coli-infection-disrupts-the-epithelial-barrier-and-activates-intrinsic-neurosecretory-reflexes-in-the-pig-colon
#23
JOURNAL ARTICLE
Sara Traserra, Sergi Casabella-Ramón, Patri Vergara, Marcel Jimenez
This study aims to assess the barrier integrity and possible activation of enteric neural pathways associated with secretion and motility in the pig colon induced by an enterotoxigenic Escherichia coli (ETEC) challenge. 50 Danbred male piglets were used for this study. 16 were challenged with an oral dose of the ETEC strain F4+ 1.5 × 109 colony-forming unit. Colonic samples were studied 4- and 9-days post-challenge using both a muscle bath and Ussing chamber. Colonic mast cells were stained with methylene blue...
2023: Frontiers in Physiology
https://read.qxmd.com/read/37277416/association-between-smoking-and-obstructive-sleep-apnea-based-on-the-stop-bang-index
#24
JOURNAL ARTICLE
Yun Seo Jang, Nataliya Nerobkova, Kyungduk Hurh, Eun-Cheol Park, Jaeyong Shin
Smoking is a risk factor for respiratory diseases, and it worsens sleep quality due to nicotine stimulation and sudden nicotine withdrawal during sleep. This can increase the severity of OSA through alterations upper airway inflammation and neuromuscular function, arousal mechanisms, and sleep architecture. Therefore, it may lead to sleep-disrupted breathing, particularly obstructive sleep apnea (OSA). Herein, this study aims to research the association between smoking and OSA through the STOP-Bang index. In this study, total sample of 3442 participants (1465 men and 1977 women) were analyzed...
June 5, 2023: Scientific Reports
https://read.qxmd.com/read/37276924/recombinant-human-neuregulin-1-alleviates-immobilization-induced-neuromuscular-dysfunction-via-neuregulin-1-erbb-signaling-pathway-in-rat
#25
JOURNAL ARTICLE
Jun Yang, Jun Cao, Su Min, Ping Li, Feng Lv, Li Ren
Immobilization-induced Neuromuscular Dysfunction (NMD) increases morbidity and mortality of patients in Intensive Care Units. However, the underlying mechanism of NMD remain poorly elucidated which limited the development of therapeutic method for NMD. Here we developed an immobilization rat model and tested the hypothesis that decreased expression of NRG-1, abnormal expression and distribution of nicotinic acetylcholine receptors (nAChRs) in skeletal muscle caused by immobilization can lead to NMD. To investigate the role of NRG-1/ErbB pathway on immobilization-induced NMD, exogenous recombinant human neuregulin-1 (rhNRG-1) was used to increase the expression of NRG-1 in skeletal muscle during immobilization...
June 3, 2023: Archives of Biochemistry and Biophysics
https://read.qxmd.com/read/37264005/structural-interplay-of-anesthetics-and-paralytics-on-muscle-nicotinic-receptors
#26
JOURNAL ARTICLE
Umang Goswami, Md Mahfuzur Rahman, Jinfeng Teng, Ryan E Hibbs
General anesthetics and neuromuscular blockers are used together during surgery to stabilize patients in an unconscious state. Anesthetics act mainly by potentiating inhibitory ion channels and inhibiting excitatory ion channels, with the net effect of dampening nervous system excitability. Neuromuscular blockers act by antagonizing nicotinic acetylcholine receptors at the motor endplate; these excitatory ligand-gated ion channels are also inhibited by general anesthetics. The mechanisms by which anesthetics and neuromuscular blockers inhibit nicotinic receptors are poorly understood but underlie safe and effective surgeries...
June 1, 2023: Nature Communications
https://read.qxmd.com/read/37240370/early-alterations-in-structural-and-functional-properties-in-the-neuromuscular-junctions-of-mutant-fus-mice
#27
JOURNAL ARTICLE
Marat A Mukhamedyarov, Aydar N Khabibrakhmanov, Venera F Khuzakhmetova, Arthur R Giniatullin, Guzalia F Zakirjanova, Nikita V Zhilyakov, Kamilla A Mukhutdinova, Dmitry V Samigullin, Pavel N Grigoryev, Andrey V Zakharov, Andrey L Zefirov, Alexey M Petrov
Amyotrophic lateral sclerosis (ALS) is manifested as skeletal muscle denervation, loss of motor neurons and finally severe respiratory failure. Mutations of RNA-binding protein FUS are one of the common genetic reasons of ALS accompanied by a 'dying back' type of degeneration. Using fluorescent approaches and microelectrode recordings, the early structural and functional alterations in diaphragm neuromuscular junctions (NMJs) were studied in mutant FUS mice at the pre-onset stage. Lipid peroxidation and decreased staining with a lipid raft marker were found in the mutant mice...
May 19, 2023: International Journal of Molecular Sciences
https://read.qxmd.com/read/37235916/discovery-and-pharmacological-characterization-of-novel-positive-allosteric-modulators-acting-on-skeletal-muscle-type-nicotinic-acetylcholine-receptors
#28
JOURNAL ARTICLE
Asako Saito, Shigeo Matsui, Ayaka Chino, Shota Sato, Nobuaki Takeshita
Skeletal muscle-type nicotinic acetylcholine receptors (m-nAChRs) are ligand-gated ion channels that open after activation by ACh and whose signals cause muscle contraction. Defects in neurotransmission are reported in disorders such as myasthenia gravis (MG) and congenital myasthenia syndromes (CMS). Although treatments for these disorders exist, therapies which significantly increase muscle strength have yet to be reported. Positive allosteric modulators (PAMs), which promote ACh signaling through AChRs, are expected to be promising therapeutic agents...
May 16, 2023: Biochemical and Biophysical Research Communications
https://read.qxmd.com/read/36994261/myasthenia-like-presentation-of-imidacloprid-toxicity
#29
Noel James, Tamilpavai Arulnambi, Parvathy K S, Nirumal Khumar, Lakshmi Narasimhan Ranganathan
Imidacloprid is a neonicotinoid insecticide highly specific to nicotinic acetylcholine receptors in insects and other invertebrates. Nicotinic receptors in mammalian species have a low affinity to neonicotinoids. However, cross-reactivity with mammalian nicotinic receptors is a major concern especially due to the propensity of this commonly used agent to persist in environmental water sources for an extended period of time. Here, we present a case report of a patient who presented to the emergency department with features suggestive of neuromuscular junction dysfunction, following exposure to imidacloprid...
February 2023: Curēus
https://read.qxmd.com/read/36975763/statin-exposure-during-pregnancy-promotes-neuromuscular-junction-alterations-in-post-partum-wistar-rats
#30
JOURNAL ARTICLE
Kevin Silva Muller, Felipe Cantore Tibúrcio, Jorge Willian Franco de Barros, Cintia Yuri Matsumura, Selma Maria Michelin Matheus
INTRODUCTION/AIMS: The mechanisms that underlie the pathogenesis of statin-associated muscle symptoms (SAMS) remain unclear. Pregnancy is associated with increased cholesterol levels. Statins may be useful during pregnancy, but their safety is uncertain. Hence, we investigated the post-partum effects of exposure to rosuvastatin and simvastatin during pregnancy in Wistar Rats, targeting the neuromuscular structures. METHODS: Twenty-one pregnant Wistar rats were divided into three groups: control (C) treated with vehicle (dimethylsulfoxide + dH20); simvastatin (S) 62...
March 28, 2023: Muscle & Nerve
https://read.qxmd.com/read/36931539/the-%C3%AE-9%C3%AE-10-acetylcholine-receptor-a-non-neuronal-nicotinic-receptor
#31
JOURNAL ARTICLE
Ana Belén Elgoyhen
Within the superfamily of pentameric ligand-gated ion channels, cholinergic nicotinic receptors (nAChRs) were classically identified to mediate synaptic transmission in the nervous system and the neuromuscular junction. The α9 and α10 nAChR subunits were the last ones to be identified. Surprisingly, they do not fall into the dichotomic neuronal/muscle classification of nAChRs. They assemble into heteropentamers with a well-established function as canonical ion channels in inner ear hair cells, where they mediate central nervous system control of auditory and vestibular sensory processing...
March 15, 2023: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://read.qxmd.com/read/36835142/clinical-and-pathologic-features-of-congenital-myasthenic-syndromes-caused-by-35-genes-a-comprehensive-review
#32
REVIEW
Kinji Ohno, Bisei Ohkawara, Xin-Ming Shen, Duygu Selcen, Andrew G Engel
Congenital myasthenic syndromes (CMS) are a heterogeneous group of disorders characterized by impaired neuromuscular signal transmission due to germline pathogenic variants in genes expressed at the neuromuscular junction (NMJ). A total of 35 genes have been reported in CMS ( AGRN, ALG14, ALG2, CHAT, CHD8, CHRNA1, CHRNB1, CHRND, CHRNE, CHRNG, COL13A1, COLQ, DOK7, DPAGT1, GFPT1, GMPPB, LAMA5, LAMB2, LRP4, MUSK, MYO9A, PLEC, PREPL, PURA, RAPSN, RPH3A, SCN4A, SLC18A3, SLC25A1, SLC5A7, SNAP25, SYT2, TOR1AIP1, UNC13A, VAMP1 )...
February 13, 2023: International Journal of Molecular Sciences
https://read.qxmd.com/read/36830985/immunological-and-structural-characterization-of-titin-main-immunogenic-region-i110-domain-is-the-target-of-titin-antibodies-in-myasthenia-gravis
#33
JOURNAL ARTICLE
Christos Stergiou, Rhys Williams, Jennifer R Fleming, Vasiliki Zouvelou, Elpinickie Ninou, Francesca Andreetta, Elena Rinaldi, Ornella Simoncini, Renato Mantegazza, Julius Bogomolovas, John Tzartos, Siegfried Labeit, Olga Mayans, Socrates Tzartos
Myasthenia gravis (MG) is an autoimmune disease caused by antibodies targeting the neuromuscular junction (NJ) of skeletal muscles. The major MG autoantigen is nicotinic acetylcholine receptor. Other autoantigens at the NJ include MuSK, LRP4 and agrin. Autoantibodies to the intra-sarcomeric striated muscle-specific gigantic protein titin, although not directed to the NJ, are invaluable biomarkers for thymoma and MG disease severity. Thymus and thymoma are critical in MG mechanisms and management. Titin autoantibodies bind to a 30 KDa titin segment, the main immunogenic region (MIR), consisting of an Ig-FnIII-FnIII 3-domain tandem, termed I109-I111...
February 3, 2023: Biomedicines
https://read.qxmd.com/read/36815443/the-role-of-rapsyn-in-neuromuscular-junction-and-congenital-myasthenic-syndrome
#34
REVIEW
Xufeng Liao, Yingxing Wang, Xinsheng Lai, Shunqi Wang
Rapsyn, an intracellular scaffolding protein associated with the postsynaptic membranes in the neuromuscular junction (NMJ), is critical for nicotinic acetylcholine receptor clustering and maintenance. Therefore, Rapsyn is essential to the NMJ formation and maintenance, and Rapsyn mutant is one of the reasons causing the pathogenies of congenital myasthenic syndrome (CMS). In addition, there is little research on Rapsyn in the central nervous system (CNS). In this review, the role of Rapsyn in the NMJ formation and the mutation of Rapsyn leading to CMS will be reviewed separately and sequentially...
February 20, 2023: Biomol Biomed
https://read.qxmd.com/read/36775959/an-update-of-the-pharmacological-treatment-options-for-generalized-myasthenia-gravis-in-adults-with-anti-acetylcholine-receptor-antibodies
#35
JOURNAL ARTICLE
Tanya R Riley, Janine S Douglas, Christopher Wang, Kiarra M Bowser
DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: This review aims to provide an update on current pharmacological agents for the management of generalized myasthenia gravis (MG)...
February 13, 2023: American Journal of Health-system Pharmacy: AJHP
https://read.qxmd.com/read/36769002/novel-organoruthenium-ii-complex-c1-selectively-inhibits-butyrylcholinesterase-without-side-effects-on-neuromuscular-transmission
#36
JOURNAL ARTICLE
Tomaž Trobec, Monika C Žužek, Kristina Sepčić, Jerneja Kladnik, Iztok Turel, Robert Frangež
Enzyme butyrylcholinesterase (BChE) shows increased activity in some brain regions after progression of Alzheimer's disease and is therefore one of the therapeutic targets for symptomatic treatment of this neurodegenerative disorder. The organoruthenium(II) complex [(η6 - p -cymene)Ru(II)(1-hydroxy-3-methoxypyridine-2(1 H )-thionato)pta]PF6 ( C1 ) was designed based on the results of our previous structure-activity studies. Inhibitory activity toward cholinesterase enzymes shows that this complex selectively, competitively, and reversibly inhibits horse serum BChE (hsBChE) with an IC50 value of 2...
January 31, 2023: International Journal of Molecular Sciences
https://read.qxmd.com/read/36650574/is-the-post-covid-19-syndrome-a-severe-impairment-of-acetylcholine-orchestrated-neuromodulation-that-responds-to-nicotine-administration
#37
JOURNAL ARTICLE
Marco Leitzke
Following a SARS-CoV-2 infection, many individuals suffer from post-COVID-19 syndrome. It makes them unable to proceed with common everyday activities due to weakness, memory lapses, pain, dyspnea and other unspecific physical complaints. Several investigators could demonstrate that the SARS-CoV-2 related spike glycoprotein (SGP) attaches not only to ACE-2 receptors but also shows DNA sections highly affine to nicotinic acetylcholine receptors (nAChRs). The nAChR is the principal structure of cholinergic neuromodulation and is responsible for coordinated neuronal network interaction...
January 18, 2023: Bioelectronic Medicine
https://read.qxmd.com/read/36602350/pharmacological-profiling-of-a-brugia-malayi-muscarinic-acetylcholine-receptor-as-a-putative-antiparasitic-target
#38
JOURNAL ARTICLE
Kendra J Gallo, Nicolas J Wheeler, Abdifatah M Elmi, Paul M Airs, Mostafa Zamanian
The diversification of anthelmintic targets and mechanisms of action will help ensure the sustainable control of nematode infections in response to the growing threat of drug resistance. G protein-coupled receptors (GPCRs) are established drug targets in human medicine but remain unexploited as anthelmintic substrates despite their important roles in nematode neuromuscular and physiological processes. Bottlenecks in exploring the druggability of parasitic nematode GPCRs include a limited helminth genetic toolkit and difficulties establishing functional heterologous expression...
January 5, 2023: Antimicrobial Agents and Chemotherapy
https://read.qxmd.com/read/36503818/a-novel-binding-site-in-the-nicotinic-acetylcholine-receptor-for-mb327-can-explain-its-allosteric-modulation-relevant-for-organophosphorus-poisoning-treatment
#39
JOURNAL ARTICLE
Jesko Kaiser, Christoph G W Gertzen, Tamara Bernauer, Georg Höfner, Karin V Niessen, Thomas Seeger, Franz F Paintner, Klaus T Wanner, Franz Worek, Horst Thiermann, Holger Gohlke
Organophosphorus compounds (OPCs) are highly toxic compounds that can block acetylcholine esterase (AChE) and thereby indirectly lead to an overstimulation of muscarinic and nicotinic acetylcholine receptors (nAChRs). The current treatment with atropine and AChE reactivators (oximes) is insufficient to prevent toxic effects, such as respiratory paralysis, after poisonings with various OPCs. Thus, alternative treatment options are required to increase treatment efficacy. Novel therapeutics, such as the bispyridinium non-oxime MB327, have been found to reestablish neuromuscular transmission by interacting directly with nAChR, probably via allosteric mechanisms...
November 26, 2022: Toxicology Letters
https://read.qxmd.com/read/36381585/mir-142a-3p-a-novel-ach-receptor-transcriptional-regulator-in-association-with-peripheral-nerve-injury
#40
JOURNAL ARTICLE
Zhidan Qi, Shen Wang, Ang Xuan, Xinyi Gu, Jin Deng, Chen Huang, Lei Zhang, Xiaofeng Yin
Long-term denervation leads to the disintegration of nicotinic acetylcholine receptor (nAChR) located at the endplate structure, which translates to deficits in functional activation despite nerve repair. Because of a lack of effective measures to protect AChR expression, we explored the effect of alterations in muscular miR-142a-3p on nAChR. In this study, we constructed a model of miR-142a-3p knockdown by transfecting a miR-142a-3p inhibitor short hairpin RNA (shRNA) into C2C12 myotubes, and we injected this miR-142a-3p inhibitor shRNA into the tibialis anterior (TA) muscle in uninjured mice and in denervated mice by transecting the sciatic nerve...
December 13, 2022: Molecular Therapy. Nucleic Acids
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