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https://www.readbyqxmd.com/read/28428759/morphological-regeneration-and-functional-recovery-of-neuromuscular-junctions-after-tourniquet-induced-injuries-in-mouse-hindlimb
#1
Huiyin Tu, Dongze Zhang, Ryan M Corrick, Robert L Muelleman, Michael C Wadman, Yu-Long Li
Tourniquet application and its subsequent release cause serious injuries to the skeletal muscle, nerve, and neuromuscular junction (NMJ) due to mechanical compression and ischemia-reperfusion (IR). Monitoring structural and functional repair of the NMJ, nerve, and skeletal muscle after tourniquet-induced injuries is beneficial in exploring potential cellular and molecular mechanisms responsible for tourniquet-induced injuries, and for establishing effective therapeutic interventions. Here, we observed long-term morphological and functional changes of the NMJ in a murine model of tourniquet-induced hindlimb injuries...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28419739/cardiac-troponin-t-and-fast-skeletal-muscle-denervation-in-ageing
#2
Zherong Xu, Xin Feng, Juan Dong, Zhong-Min Wang, Jingyun Lee, Cristina Furdui, Daniel Clark Files, Kristen M Beavers, Stephen Kritchevsky, Carolanne Milligan, Jian-Ping Jin, Osvaldo Delbono, Tan Zhang
BACKGROUND: Ageing skeletal muscle undergoes chronic denervation, and the neuromuscular junction (NMJ), the key structure that connects motor neuron nerves with muscle cells, shows increased defects with ageing. Previous studies in various species have shown that with ageing, type II fast-twitch skeletal muscle fibres show more atrophy and NMJ deterioration than type I slow-twitch fibres. However, how this process is regulated is largely unknown. A better understanding of the mechanisms regulating skeletal muscle fibre-type specific denervation at the NMJ could be critical to identifying novel treatments for sarcopenia...
April 16, 2017: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/28386022/multiple-roles-of-integrin-%C3%AE-3-at-the-neuromuscular-junction
#3
Jacob A Ross, Richard G Webster, Tanguy Lechertier, Louise E Reynolds, Mark Turmaine, Maximilien Bencze, Yalda Jamshidi, Hakan Cetin, Francesco Muntoni, David Beeson, Kairbaan Hodilvala-Dilke, Francesco J Conti
The neuromuscular junction (NMJ) is the synapse between motoneuron and skeletal muscle, and is responsible for eliciting muscle contraction. Neurotransmission at synapses depends on the release of synaptic vesicles at sites called active zones (AZs). Various proteins of the extracellular matrix are crucial for NMJ development; however little is known about the identity and functions of the receptors that mediate their effects. Using genetically modified mice, we find that integrin-α3, an adhesion receptor at the presynaptic membrane, is involved in the localisation of AZ components and efficient synaptic vesicle release...
April 6, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28379367/a-drosophila-model-of-als-reveals-a-partial-loss-of-function-of-causative-human-pfn1-mutants
#4
Chi-Hong Wu, Anthony Giampetruzzi, Helene Tran, Claudia Fallini, Fen-Biao Gao, John E Landers
Mutations in the profilin 1 (PFN1) gene are causative for familial amyotrophic lateral sclerosis (fALS). However, it is still not fully understood how these mutations lead to neurodegeneration. To address this question, we generated a novel Drosophila model expressing human wild-type and ALS-causative PFN1 mutants. We show that at larval neuromuscular junctions (NMJ), motor neuron expression of wild-type human PFN1 increases the number of ghost boutons, active zone density, F-actin content, and the formation of filopodia...
April 3, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28379354/motor-neuronal-repletion-of-the-nmj-organizer-agrin-modulates-the-severity-of-the-spinal-muscular-atrophy-disease-phenotype-in-model-mice
#5
Jeong-Ki Kim, Charlotte Caine, Tomoyuki Awano, Ruth Herbst, Umrao R Monani
Spinal muscular atrophy (SMA) is a common and often fatal neuromuscular disorder caused by low levels of the Survival Motor Neuron (SMN) protein. Amongst the earliest detectable consequences of SMN deficiency are profound defects of the neuromuscular junctions (NMJs). In model mice these synapses appear disorganized, fail to mature and are characterized by poorly arborized nerve terminals. Given one role of the SMN protein in orchestrating the assembly of spliceosomal snRNP particles and subsequently regulating the alternative splicing of pre-mRNAs, a plausible link between SMN function and the distal neuromuscular SMA phenotype is an incorrectly spliced transcript or transcripts involved in establishing or maintaining NMJ structure...
March 31, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28375749/immunization-with-recombinantly-expressed-lrp4-induces-experimental-autoimmune-myasthenia-gravis-in-c57bl-6-mice
#6
Canan Ulusoy, Filiz Çavuş, Vuslat Yılmaz, Erdem Tüzün
BACKGROUND: Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction (NMJ), characterized with muscle weakness. While MG develops due to acetylcholine receptor (AChR) antibodies in most patients, antibodies to muscle-specific receptor tyrosine kinase (MuSK) or low-density lipoprotein receptor-related protein 4 (LRP4) may also be identified. Experimental autoimmune myasthenia gravis (EAMG) has been previously induced by both LRP4 immunization and passive transfer of LRP4 antibodies...
April 4, 2017: Immunological Investigations
https://www.readbyqxmd.com/read/28371371/zebrafish-mecp2-is-required-for-proper-axonal-elongation-of-motor-neurons-and-synapse-formation
#7
Keisuke Nozawa, Yanbin Lin, Ryota Kubodera, Yuki Shimizu, Hideomi Tanaka, Toshio Ohshima
Rett syndrome is a severe neurodevelopmental disorder. It is caused by a mutation in methyl-CpG binding protein 2 (MecP2), a transcriptional regulator that recruits protein complexes involved in histone modification and chromatin remodeling. However, the role of Mecp2 in Rett syndrome remains unclear. In this study, we investigated the function of Mecp2 in neuronal development using zebrafish embryos. Mecp2 expression was detected ubiquitously in the central nervous system and muscles at 28 h postfertilization (hpf)...
April 2, 2017: Developmental Neurobiology
https://www.readbyqxmd.com/read/28370195/axonal-domain-disorganization-in-caspr1-and-caspr2-mutant-myelinated-axons-affects-neuromuscular-junction-integrity-leading-to-muscle-atrophy
#8
Julia Saifetiarova, Xi Liu, Anna M Taylor, Jie Li, Manzoor A Bhat
Bidirectional interactions between neurons and myelinating glial cells result in formation of axonal domains along myelinated fibers. Loss of axonal domains leads to detrimental consequences on nerve structure and function, resulting in reduced conductive properties and the diminished ability to reliably transmit signals to the targets they innervate. Thus, impairment of peripheral myelinated axons that project to the surface of muscle fibers and form neuromuscular junction (NMJ) synapses leads to muscle dysfunction...
April 3, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28364093/spatial-distribution-and-molecular-dynamics-of-dystrophin-glycoprotein-components-at-the-neuromuscular-junction-in-vivo
#9
Mohamed Aittaleb, Isabel Martinez-Pena Y Valenzuela, Mohammed Akaaboune
Bimolecular fluorescence complementation (BiFC) approach was used to study the molecular interactions between different components of the postsynaptic protein complex at the neuromuscular junction of living mice. Here, we showed that rapsyn forms complex with both α-dystrobrevin and α-syntrophin at the crests of junctional folds. The linkage of rapsyn to α-syntrophin and/or α-dystrobrevin is mediated by utrophin, a protein localized at AChR-rich domain. In mice deficient in α-syntrophin, in which utrophin is no longer present at the synapse, rapsyn interaction with α- dystrobrevin was completely abolished...
March 31, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28348167/wnts-contribute-to-neuromuscular-junction-formation-through-distinct-signaling-pathways
#10
Julien Messéant, Jérôme Ezan, Perrine Delers, Konstantin Glebov, Carmen Marchiol, Franck Lager, Gilles Renault, Fadel Tissir, Mireille Montcouquiol, Nathalie Sans, Claire Legay, Laure Strochlic
Understanding the developmental steps shaping the formation of the neuromuscular junction (NMJ) connecting motoneurons to skeletal muscle fibers, is critical. Wnt morphogens are key players in the formation of this specialized peripheral synapse. Yet, the individual and collaborative functions of Wnts as well as their downstream pathways remain poorly understood at the NMJ. Here, we demonstrate through Wnt4 and Wnt11 gain of function studies in culture or in mice that Wnts enhance acetylcholine receptor (AChR) clustering and motor axon outgrowth...
March 27, 2017: Development
https://www.readbyqxmd.com/read/28337539/homer1-vesl-1-in-the-rat-esophagus-focus-on-myenteric-plexus-and-neuromuscular-junction
#11
J Zimmermann, W L Neuhuber, M Raab
Homer1, a scaffolding protein of the postsynaptic density (PSD), enriched at excitatory synapses is known to anchor and modulate group I metabotropic glutamate receptors (mGluRs) and different channel- and receptor-proteins. Homer proteins are expressed in neurons of different brain regions, but also in non-neuronal tissues like skeletal muscle. Occurrence and location of Homer1 and mGluR5 in myenteric plexus and neuromuscular junctions (NMJ) of rat esophagus have yet not been characterized. We located Homer1 and mGluR5 immunoreactivity (-iry) in rat esophagus and focused on myenteric neurons, intraganglionic laminar endings (IGLEs) and NMJs, using double- and triple-label immunohistochemistry and confocal laser scanning microscopy...
March 23, 2017: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/28329051/caloric-restriction-mimetics-slow-aging-of-neuromuscular-synapses-and-muscle-fibers
#12
Jessica Stockinger, Nicholas Maxwell, Dillon Shapiro, Rafael deCabo, Gregorio Valdez
Resveratrol and metformin have been shown to mimic some aspects of caloric restriction and exercise. However, it remains unknown if these molecules also slow age-related synaptic degeneration, as previously shown for caloric restriction and exercise. In this study, we examined the structural integrity of neuromuscular junctions (NMJs) in 2-year-old mice treated with resveratrol and metformin starting at 1 year of age. We found that resveratrol significantly slows aging of NMJs in the extensor digitorum longus muscle of 2-year-old mice...
March 7, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28301326/functional-decline-at-the-aging-neuromuscular-junction-is-associated-with-altered-laminin-%C3%AE-4-expression
#13
Kah Meng Lee, Kirat K Chand, Luke A Hammond, Nickolas A Lavidis, Peter G Noakes
Laminin-α4 is involved in the alignment of active zones to postjunctional folds at the neuromuscular junction (NMJ). Prior study has implicated laminin-α4 in NMJ maintenance, with altered NMJ morphology observed in adult laminin-α4 deficient mice (lama4(-/-)). The present study further investigated the role of laminin-α4 in NMJ maintenance by functional characterization of transmission properties, morphological investigation of synaptic proteins including synaptic laminin-α4, and neuromotor behavioral testing...
March 14, 2017: Aging
https://www.readbyqxmd.com/read/28298885/functional-roles-of-the-interaction-of-app-and-lipoprotein-receptors
#14
REVIEW
Theresa Pohlkamp, Catherine R Wasser, Joachim Herz
The biological fates of the key initiator of Alzheimer's disease (AD), the amyloid precursor protein (APP), and a family of lipoprotein receptors, the low-density lipoprotein (LDL) receptor-related proteins (LRPs) and their molecular roles in the neurodegenerative disease process are inseparably interwoven. Not only does APP bind tightly to the extracellular domains (ECDs) of several members of the LRP group, their intracellular portions are also connected through scaffolds like the one established by FE65 proteins and through interactions with adaptor proteins such as X11/Mint and Dab1...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28286469/the-ih-channel-gene-promotes-synaptic-transmission-and-coordinated-movement-in-drosophila-melanogaster
#15
Andrew P Hegle, C Andrew Frank, Anthony Berndt, Markus Klose, Douglas W Allan, Eric A Accili
Hyperpolarization-activated cyclic nucleotide-gated "HCN" channels, which underlie the hyperpolarization-activated current (Ih), have been proposed to play diverse roles in neurons. The presynaptic HCN channel is thought to both promote and inhibit neurotransmitter release from synapses, depending upon its interactions with other presynaptic ion channels. In larvae of Drosophila melanogaster, inhibition of the presynaptic HCN channel by the drug ZD7288 reduces the enhancement of neurotransmitter release at motor terminals by serotonin but this drug has no effect on basal neurotransmitter release, implying that the channel does not contribute to firing under basal conditions...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28276271/an-anthocyanin-enriched-extract-from-strawberries-delays-disease-onset-and-extends-survival-in-the-hsod1-g93a-mouse-model-of-amyotrophic-lateral-sclerosis
#16
Aimee N Winter, Erika K Ross, Heather M Wilkins, Trisha R Stankiewicz, Tyler Wallace, Keith Miller, Daniel A Linseman
OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease resulting from the death of motor neurons in the brain, brain stem, and spinal cord. Several processes such as oxidative stress, neuroinflammation, and neuronal apoptosis, contribute to disease progression. Anthocyanins are flavonoid compounds derived from fruits and vegetables that possess antioxidant, anti-inflammatory, and anti-apoptotic abilities. Thus, these unique compounds may provide therapeutic benefit for the treatment of ALS...
March 9, 2017: Nutritional Neuroscience
https://www.readbyqxmd.com/read/28256749/increased-postsynaptic-ca-2-reduces-mini-frequency-at-the-drosophila-larval-nmj
#17
Andrew S Powers, Jeffrey Grizzaffi, Gregory A Lnenicka
No abstract text is available yet for this article.
March 3, 2017: Synapse
https://www.readbyqxmd.com/read/28253535/homozygous-mutations-in-vamp1-cause-a-presynaptic-congenital-myasthenic-syndrome
#18
Vincenzo Salpietro, Weichun Lin, Andrea Delle Vedove, Markus Storbeck, Yun Liu, Stephanie Efthymiou, Andreea Manole, Sarah Wiethoff, Qiaohong Ye, Anand Saggar, Kenneth McElreavey, Shyam S Krishnakumar, Matthew Pitt, Oscar D Bello, James E Rothman, Lina Basel-Vanagaite, Monika Weisz Hubshman, Sharon Aharoni, Adnan Y Manzur, Brunhilde Wirth, Henry Houlden
We report 2 families with undiagnosed recessive presynaptic congenital myasthenic syndrome (CMS). Whole exome or genome sequencing identified segregating homozygous variants in VAMP1: c.51_64delAGGTGGGGGTCCCC in a Kuwaiti family and c.146G>C in an Israeli family. VAMP1 is crucial for vesicle fusion at presynaptic neuromuscular junction (NMJ). Electrodiagnostic examination showed severely low compound muscle action potentials and presynaptic impairment. We assessed the effect of the nonsense mutation on mRNA levels and evaluated the NMJ transmission in VAMP1(lew/lew) mice, observing neurophysiological features of presynaptic impairment, similar to the patients...
April 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28245533/neuregulin1-fine-tunes-pre-post-and-perisynaptic-neuromuscular-junction-development
#19
Jiajing Wang, Fei Song, Jeffrey A Loeb
BACKGROUND: Neuromuscular junction (NMJ) development is a multistep process mediated by coordinated interactions between the nerve terminal, target muscle, and perisynaptic Schwann cell that require constant back-and-forth communication. Retrograde and anterograde growth and differentiation factors have been postulated to participate in this communication. While neuregulin1 (NRG1) has been shown to be potent anterograde signal that activates acetylcholine receptor (AChR) transcription and clustering in vitro, its roles in NMJ development in vivo remain elusive...
February 28, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28245518/altered-translational-repression-of-an-rna-binding-protein-elav-by-aoa2-causative-senataxin-mutation
#20
Saumitra Dey Choudhury, Ancy Vs, Zeeshan Mushtaq, Vimlesh Kumar
Mutations in Senataxin (SETX) gene causes two types of neurological disorders, Amyotrophic Lateral Sclerosis (ALS4) and Ataxia with Oculomotor Apraxia type 2 (AOA2). Recent studies in cultured cells suggest that SETX plays a crucial role at the interface of transcription and the DNA damage response. Whether SETX can alter translational of specific RNA is not known. In this study, we report that expressing AOA2-causative truncated form of human SETX in Drosophila neurons alters the development of neuromuscular junction (NMJ) synapses...
February 28, 2017: Synapse
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