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https://www.readbyqxmd.com/read/29326174/muscle-nicotinic-acetylcholine-receptors-may-mediate-trans-synaptic-signaling-at-the-mouse-neuromuscular-junction
#1
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 neuromuscular junction 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...
January 11, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29323161/lack-of-fgf18-causes-abnormal-clustering-of-motor-nerve-terminals-at-the-neuromuscular-junction-with-reduced-acetylcholine-receptor-clusters
#2
Kenyu Ito, Bisei Ohkawara, Hideki Yagi, Hiroaki Nakashima, Mikito Tsushima, Kyotaro Ota, Hiroyuki Konishi, Akio Masuda, Shiro Imagama, Hiroshi Kiyama, Naoki Ishiguro, Kinji Ohno
FGF receptor 2 is involved in the formation of the neuromuscular junction (NMJ), but its in vivo ligand remains to be determined. Laser capture microdissection of the mouse spinal motor neurons (SMNs) revealed that Fgf18 mRNA is highly expressed in SMNs in adults. Expression of Fgf18 mRNA was the highest in the spinal cord at embryonic day (E) 15.5, which gradually decreased to postnatal day 7. FGF18 protein was localized at the NMJs of the tibialis anterior muscle at E18.5 and in adults. Fgf18-/- mice at E18...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29317220/acamprosate-rescues-neuronal-defects-in-the-drosophila-model-of-fragile-x-syndrome
#3
Russell L Hutson, Rachel L Thompson, Andrew P Bantel, Charles R Tessier
AIMS: Several off-label studies have shown that acamprosate can provide some clinical benefits in youth with Fragile X Syndrome (FXS), an autism spectrum disorder caused by loss of function of the highly conserved FMR1 gene. This study investigated the ability of acamprosate to rescue cellular, molecular and behavioral defects in the Drosophila model of FXS. MAIN METHODS: A high (100μM) and low (10μM) dose of acamprosate was fed to Drosophila FXS (dfmr1 null) or genetic control (w1118) larvae and then analyzed in multiple paradigms...
January 6, 2018: Life Sciences
https://www.readbyqxmd.com/read/29305005/the-composition-development-and-regeneration-of-neuromuscular-junctions
#4
Wenxuan Liu, Joe V Chakkalakal
The neuromuscular junction (NMJ) is the specialized site that connects the terminal of a motor neuron axon to skeletal muscle. As a synapse NMJ integrity is essential for transducing motor neuron signals that initiate skeletal muscle contraction. Many diseases and skeletal muscle aging are linked to impaired NMJ function and the associated muscle wasting. In this chapter we review the components of an NMJ and, the processes of NMJ development, maturation, and regeneration. Also, we briefly discuss the cellular and molecular mechanisms of NMJ decline in the context of disease and aging...
2018: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/29295857/defects-in-synaptic-transmission-at-the-neuromuscular-junction-precedes-motor-deficits-in-a-tdp-43q331k-transgenic-mouse-model-of-amyotrophic-lateral-sclerosis
#5
Kirat K Chand, Kah Meng Lee, John D Lee, Hao Qiu, Emily F Willis, Nickolas A Lavidis, Massimo A Hilliard, Peter G Noakes
Transactive response DNA-binding protein-43 (TDP-43) is involved in gene regulation via the control of RNA transcription, splicing, and transport. TDP-43 is a major protein component of ubiquinated inclusions that are found in amyotrophic lateral sclerosis (ALS); however, the function of TDP-43 at the neuromuscular junction (NMJ) and its role in ALS pathogenesis is largely unknown. Here, we show that TDP-43Q331K mutation in mice resulted in impaired neurotransmission by age 3 mo, preceding deficits in motor function and motor neuron loss, which were observed from age 10 mo...
January 2, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29291259/age-related-changes-in-the-structure-and-function-of-mammalian-neuromuscular-junctions
#6
REVIEW
Silvia Willadt, Mark Nash, Clarke Slater
As mammals age, their neuromuscular junctions (NMJs) change their form, with an increasingly complex system of axonal branches innervating increasingly fragmented regions of postsynaptic differentiation. It has been suggested that this remodeling is associated with impairment of neuromuscular transmission and that this contributes to age-related muscle weakness in mammals, including humans. Here, we review previous work on NMJ aging, most of which has focused on either structure or function, as well as a new study aimed at seeking correlation between the structure and function of individual NMJs...
December 31, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29282074/the-rap-activator-gef26-regulates-synaptic-growth-and-neuronal-survival-via-inhibition-of-bmp-signaling
#7
Keunjung Heo, Minyeop Nahm, Min-Jung Lee, Young-Eun Kim, Chang-Seok Ki, Seung Hyun Kim, Seungbok Lee
In Drosophila, precise regulation of BMP signaling is essential for normal synaptic growth at the larval neuromuscular junction (NMJ) and neuronal survival in the adult brain. However, the molecular mechanisms underlying fine-tuning of BMP signaling in neurons remain poorly understood. We show that loss of the Drosophila PDZ guanine nucleotide exchange factor Gef26 significantly increases synaptic growth at the NMJ and enhances BMP signaling in motor neurons. We further show that Gef26 functions upstream of Rap1 in motor neurons to restrain synaptic growth...
December 28, 2017: Molecular Brain
https://www.readbyqxmd.com/read/29277489/c-547-a-6-methyluracil-derivative-with-long-lasting-binding-and-rebinding-on-acetylcholinesterase-pharmacokinetic-and-pharmacodynamic-studies
#8
Konstantin Petrov, Irina Zueva, Irina Kovyazina, Igor Sedov, Sofya Lushchekina, Alexandra Kharlamova, Oksana Lenina, Sergei Koshkin, Yurii Shtyrlin, Evgeny Nikolsky, Patrick Masson
C-547, a potent slow-binding inhibitor of acetylcholinesterase (AChE) was intravenously administered to rat (0.05 mg/kg). Pharmacokinetic profiles were determined in blood and different organs: extensor digitorum longus muscle, heart, liver, lungs and kidneys as a function of time. Pharmacokinetics (PK) was studied using non-compartmental and compartmental analyses. A 3-compartment model describes PK in blood. Most of injected C-547 binds to albumin in the bloodstream. The steady-state volume of distribution (3800 ml/kg) is 15 times larger than the distribution volume, indicating a good tissue distribution...
December 22, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29258853/drosophila-active-zones-from-molecules-to-behaviour
#9
REVIEW
Nadine Ehmann, David Owald, Robert J Kittel
In a constantly changing environment, neuronal circuits need to be updated and adjusted to elicit directed actions. Synaptic plasticity plays an important role in modulating such globally and locally acting networks. The active zone (AZ) is a protein-rich compartment of chemical synapses, where precisely orchestrated molecular interactions control synaptic vesicle (SV) fusion with the presynaptic membrane. The subsequent release of neurotransmitter substances onto postsynaptic receptor fields forms the basis of neuronal communication...
December 16, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/29249293/epigenetic-crosstalk-pharmacological-inhibition-of-hdacs-can-rescue-defective-synaptic-morphology-and-neurotransmission-phenotypes-associated-with-loss-of-the-chromatin-reader-kismet
#10
REVIEW
Nina K Latcheva, Jennifer M Viveiros, Edward A Waddell, Phuong T T Nguyen, Faith L W Liebl, Daniel R Marenda
We are beginning to appreciate the complex mechanisms by which epigenetic proteins control chromatin dynamics to tightly regulate normal development. However, the interaction between these proteins, particularly in the context of neuronal function, remains poorly understood. Here, we demonstrate that the activity of histone deacetylases (HDACs) opposes that of a chromatin remodeling enzyme at the Drosophila neuromuscular junction (NMJ). Pharmacological inhibition of HDAC function reverses loss of function phenotypes associated with Kismet, a chromodomain helicase DNA-binding (CHD) protein...
December 14, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29235536/genetically-unmatched-human-ipsc-and-esc-exhibit-equivalent-gene-expression-and-neuronal-differentiation-potential
#11
Hany E Marei, A Althani, S Lashen, C Cenciarelli, Anwarul Hasan
The potential uniformity between differentiation and therapeutic potential of human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) remains debatable. We studied the gene expression profiles, pathways analysis and the ability to differentiated into neural progenitor cells (NPCs) and motor neurons (MNs) of genetically unmatched integration-free hiPSC versus hESC to highlight possible differences/similarities between them at the molecular level. We also provided the functional information of the neurons derived from the different hESCs and hiPSCs lines using the Neural Muscular Junction (NMJ) Assay...
December 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29230271/the-role-of-oxidative-stress-in-decreased-acetylcholinesterase-activity-at-the-neuromuscular-junction-of-the-diaphragm-during-sepsis
#12
Hua Liu, Jin Wu, Jun-Yan Yao, Hong Wang, Shi-Tong Li
Our recent study demonstrated that acetylcholinesterase (AChE) activity at the neuromuscular junction (NMJ) of the diaphragm decreased during sepsis. However, the mechanisms were not clearly identified. In this study, we aimed to investigate whether the decreased AChE activity was related to oxidative stress by observing AChE activity in different grades of sepsis induced by caecal ligation and puncture (CLP). At 24 h after surgery, an assay of thiobarbituric acid reactive species (TBARS) and protein carbonyls, as well as the myeloperoxidase (MPO), superoxide dismutase (SOD), and catalase (CAT) activity, was conducted...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29226485/immunohistologic-analysis-of-spontaneous-recurrent-laryngeal-nerve-reinnervation-in-a-rat-model
#13
Andrew J Rosko, Robbi A Kupfer, Sang S Oh, Catherine T Haring, Eva L Feldman, Norman D Hogikyan
OBJECTIVE: After recurrent laryngeal nerve injury (RLN), spontaneous reinnervation of the larynx occurs with input from multiple sources. The purpose of this study was to determine the timing and efficiency of reinnervation across a resected RLN segment in a rat model of RLN injury. STUDY DESIGN: Animal study. METHODS: Twelve male 60-day-old Sprague Dawley rats underwent resection of a 5-mm segment of the right RLN. Rats were sacrificed at 1, 2, 4, and 12 weeks after nerve injury to harvest the larynx and trachea for immunohistologic analysis...
December 11, 2017: Laryngoscope
https://www.readbyqxmd.com/read/29217522/drosophila-syd-1-has-rhogap-activity-that-is-required-for-presynaptic-clustering-of-bruchpilot-elks-but-not-neurexin-1
#14
Michael A Spinner, David A Walla, Tory G Herman
Syd-1 proteins are required for presynaptic development in worm, fly, and mouse. Syd-1s in all three species contain a Rho GTPase activating protein (GAP)-like domain of unclear significance. Invertebrate Syd-1s are thought to lack GAP activity, and mouse mSYD1A has GAP activity that is thought to be dispensible for its function. Here we show that Drosophila melanogaster Syd-1 can interact with all six fly Rhos and has GAP activity toward Rac1 and Cdc42. During development, fly Syd-1 clusters multiple presynaptic proteins at the neuromuscular junction (NMJ), including the cell adhesion molecule Neurexin (Nrx-1) and the active zone (AZ) component Bruchpilot (Brp), both of which Syd-1 binds directly...
December 7, 2017: Genetics
https://www.readbyqxmd.com/read/29201547/decremental-responses-in-patients-with-motor-neuron-disease
#15
Mohammed H Alanazy, Janka Hegedus, Chris White, Lawrence Korngut
Objective: Involvement of the neuromuscular junction (NMJ) in amyotrophic lateral sclerosis (ALS) has been reported and is increasingly recognized as an important pathophysiological aspect. The relationship between decrement and clinical measures for possible application as a biomarker has not been comprehensively explored. Methods: We performed routine repetitive nerve stimulation (RNS) of three nerves on patients with ALS. We captured measures of muscle strength, grip strength, fatigability, and calculated slow vital capacity (SVC) rates of change assessing for associations...
November 2017: Brain and Behavior
https://www.readbyqxmd.com/read/29195055/neuromuscular-junction-formation-aging-and-disorders
#16
Lei Li, Wen-Cheng Xiong, Lin Mei
Synapses, the fundamental unit in neuronal circuits, are critical for learning and memory, perception, thinking, and reaction. The neuromuscular junction (NMJ) is a synapse formed between motoneurons and skeletal muscle fibers that is wrapped by Schwann cells (SCs). It is essential for controlling muscle contraction. NMJ formation requires intimate interactions among motoneurons, muscles, and SCs. Deficits in NMJ formation and maintenance cause neuromuscular disorders, including congenital myasthenic syndrome and myasthenia gravis...
December 1, 2017: Annual Review of Physiology
https://www.readbyqxmd.com/read/29194538/mitochondrial-abnormalities-and-disruption-of-the-neuromuscular-junction-precede-the-clinical-phenotype-and-motor-neuron-loss-in-hfuswt-transgenic-mice
#17
Eva So, Jacqueline C Mitchell, Caroline Memmi, George Chennell, Gema Vizcay-Barrena, Leanne Allison, Christopher E Shaw, Caroline Vance
FUS mislocalisation and cytoplasmic aggregation are hallmark pathologies in FUS-related amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Many of the mechanistic hypotheses have focused on a loss of nuclear function in the FUS-opathies, implicating dysregulated RNA transcription and splicing in driving neurodegeneration. Recent studies describe an additional somato-dendritic localisation for FUS in the cerebral cortex implying a regulatory role in mRNA transport and local translation at the synapse...
November 28, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29193204/engineered-agrin-attenuates-the-severity-of-experimental-autoimmune-myasthenia-gravis
#18
Zhiguo Li, Minshu Li, Kristofer Wood, Steffan Hettwer, Suraj A Muley, Fu-Dong Shi, Qiang Liu, Shafeeq S Ladha
Introduction-Agrin is essential for the formation and maintenance of neuromuscular junctions (NMJs). NT-1654 is a C-terminal fragment of mouse neural agrin. In this study, we determined the effects of NT-1654 on the severity of experimental autoimmune myasthenia gravis (EAMG). Methods-EAMG was induced in female Lewis rats by immunization with the Torpedo acetylcholine receptor (tAChR) and complete Freund's adjuvant. NT-1654 was dissolved in PBS and injected daily s.c. into tAChR immunized rats during the first 10 days after immunization, and then every other day for the following 20 days...
November 28, 2017: Muscle & Nerve
https://www.readbyqxmd.com/read/29186674/cellular-and-molecular-anatomy-of-the-human-neuromuscular-junction
#19
Ross A Jones, Carl Harrison, Samantha L Eaton, Maica Llavero Hurtado, Laura C Graham, Leena Alkhammash, Oladayo A Oladiran, Andy Gale, Douglas J Lamont, Hamish Simpson, Martin W Simmen, Christian Soeller, Thomas M Wishart, Thomas H Gillingwater
The neuromuscular junction (NMJ) plays a fundamental role in transferring information from lower motor neuron to skeletal muscle to generate movement. It is also an experimentally accessible model synapse routinely studied in animal models to explore fundamental aspects of synaptic form and function. Here, we combined morphological techniques, super-resolution imaging, and proteomic profiling to reveal the detailed cellular and molecular architecture of the human NMJ. Human NMJs were significantly smaller, less complex, and more fragmented than mouse NMJs...
November 28, 2017: Cell Reports
https://www.readbyqxmd.com/read/29168874/bioreactor-model-of-neuromuscular-junction-with-electrical-stimulation-for-pharmacological-potency-testing
#20
Surapon N Charoensook, Damian J Williams, Syandan Chakraborty, Kam W Leong, Gordana Vunjak-Novakovic
In vitro models of the neuromuscular junction (NMJ) are emerging as a valuable tool to study synaptogenesis, synaptic maintenance, and pathogenesis of neurodegenerative diseases. Many models have previously been developed using a variety of cell sources for skeletal muscle and motoneurons. These models can advanced by integrating beneficial features of the native developmental milieu of the NMJ. We created a functional in vitro model of NMJ by bioreactor cultivation of transdifferentiated myocytes and stem cell-derived motoneurons, in the presence of electrical stimulation...
November 23, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
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