scholarly journals Murine muscle stem cell response to perturbations of the neuromuscular junction are attenuated with aging

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Jacqueline Larouche ◽  
Mahir Mohiuddin ◽  
Jeongmoon J Choi ◽  
Peter J Ulintz ◽  
Paula M Fraczek ◽  
...  
Keyword(s):  
Neuromuscular Junction ◽  
Motor Neurons ◽  
Neuromuscular Diseases ◽  
Lineage Tracing ◽  
Genetic Rescue ◽  
Muscle Stem Cells ◽  
Transgenic Murine Model ◽  
And Function ◽  
The Relationship

During aging and neuromuscular diseases, there is a progressive loss of skeletal muscle volume and function impacting mobility and quality of life. Muscle loss is often associated with denervation and a loss of resident muscle stem cells (satellite cells or MuSCs), however, the relationship between MuSCs and innervation has not been established. Herein, we administered severe neuromuscular trauma to a transgenic murine model that permits MuSC lineage tracing. We show that a subset of MuSCs specifically engraft in a position proximal to the neuromuscular junction (NMJ), the synapse between myofibers and motor neurons, in healthy young adult muscles. In aging and in a mouse model of neuromuscular degeneration (Cu/Zn superoxide dismutase knockout – Sod1-/-), this localized engraftment behavior was reduced. Genetic rescue of motor neurons in Sod1-/- mice reestablished integrity of the NMJ in a manner akin to young muscle and partially restored MuSC ability to engraft into positions proximal to the NMJ. Using single cell RNA-sequencing of MuSCs isolated from aged muscle, we demonstrate that a subset of MuSCs are molecularly distinguishable from MuSCs responding to myofiber injury and share similarity to synaptic myonuclei. Collectively, these data reveal unique features of MuSCs that respond to synaptic perturbations caused by aging and other stressors.

scholarly journals Single Cell Deconstruction of Muscle Stem Cell Heterogeneity During Aging Reveals Sensitivity to the Neuromuscular Junction

2020 ◽  
Author(s):  
Peter J. Ulintz ◽  
Jacqueline Larouche ◽  
Mahir Mohiuddin ◽  
Jesus Castor Macias ◽  
Sarah J. Kurpiers ◽  
...  
Keyword(s):  
Neuromuscular Junction ◽  
Single Cell ◽  
Motor Neurons ◽  
Satellite Cells ◽  
Neural Control ◽  
Neuromuscular Diseases ◽  
Neuromuscular Synapse ◽  
List Type ◽  
Genetic Rescue ◽  
Before And After

AbstractDuring aging and neuromuscular diseases, there is a progressive loss of skeletal muscle volume and function in that impacts mobility and quality of life. Muscle loss is often associated with denervation and a loss of resident muscle stem cells (satellite cells or MuSCs), but the relationship between MuSCs and neural control has not been established. Herein, using a combination of single-cell transcriptomic analysis, high-resolution immunofluorescence imaging and transgenic young and aged mice as well as from mice with neuromuscular degeneration (Sod1-/-), a compensatory neuro-responsive function for a subset of MuSCs was identified. Genetic rescue of motor neurons in Sod1-/- mice reduced this subset of MuSCs and restored integrity of the neuromuscular junction (NMJ) in a manner akin to young muscle. Administration of severe neuromuscular trauma induced young MuSCs to specifically engraft in a position proximal to the NMJ but in aging, this behavior was abolished. Contrasting the expression programs of young and aged MuSCs after muscle injury at the single cell level, we observed distinctive gene expression programs between responses to neuro-muscular degeneration and muscle trauma. Collectively, these data reveal MuSCs sense synaptic perturbations during aging and neuro-muscular deterioration, and can exert support for the NMJ, particularly in young muscle.HighlightsTranscriptional landscapes of single satellite cells from different ages before and after injury as well as neurodegenerative models before and after nervous rescueA population of satellite cells reside in close proximity to neuromuscular synapse, which are lost with ageDenervation promotes satellite cell engraftment into post-synaptic regions of young as opposed to aged muscle

scholarly journals Tenectin recruits integrin to stabilize bouton architecture and regulate vesicle release at the Drosophila neuromuscular junction

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Qi Wang ◽  
Tae Hee Han ◽  
Peter Nguyen ◽  
Michal Jarnik ◽  
Mihaela Serpe
Keyword(s):  
Neuromuscular Junction ◽  
Motor Neurons ◽  
Synaptic Cleft ◽  
Membrane Skeleton ◽  
Biologically Active ◽  
Striated Muscles ◽  
Local Engagement ◽  
Synaptic Junctions ◽  
Synaptic Boutons ◽  
And Function

Assembly, maintenance and function of synaptic junctions depend on extracellular matrix (ECM) proteins and their receptors. Here we report that Tenectin (Tnc), a Mucin-type protein with RGD motifs, is an ECM component required for the structural and functional integrity of synaptic specializations at the neuromuscular junction (NMJ) in Drosophila. Using genetics, biochemistry, electrophysiology, histology and electron microscopy, we show that Tnc is secreted from motor neurons and striated muscles and accumulates in the synaptic cleft. Tnc selectively recruits αPS2/βPS integrin at synaptic terminals, but only the cis Tnc/integrin complexes appear to be biologically active. These complexes have distinct pre- and postsynaptic functions, mediated at least in part through the local engagement of the spectrin-based membrane skeleton: the presynaptic complexes control neurotransmitter release, while postsynaptic complexes ensure the size and architectural integrity of synaptic boutons. Our study reveals an unprecedented role for integrin in the synaptic recruitment of spectrin-based membrane skeleton.

scholarly journals Neto-α controls synapse organization and homeostasis at the Drosophila neuromuscular junction

2019 ◽  
Author(s):  
Tae Hee Han ◽  
Rosario Vicidomini ◽  
Cathy Isaura Ramos ◽  
Qi Wang ◽  
Peter Nguyen ◽  
...  
Keyword(s):  
Neuromuscular Junction ◽  
Motor Neurons ◽  
Neurotransmitter Release ◽  
Cell Biology ◽  
Expression Patterns ◽  
Dependent Manner ◽  
Independent Function ◽  
Postsynaptic Receptors ◽  
Auxiliary Protein ◽  
And Function

SummaryGlutamate receptor auxiliary proteins control receptor distribution and function, ultimately controlling synapse assembly, maturation and plasticity. At the Drosophila neuromuscular junction (NMJ), a synapse with both pre- and post-synaptic kainate-type glutamate receptors (KARs), we show that the auxiliary protein Neto evolved functionally distinct isoforms to modulate synapse development and homeostasis. Using genetics, cell biology and electrophysiology we demonstrate that Neto-α functions on both sides of the NMJ. In muscle, Neto-α limits the size of the postsynaptic receptors field. In motor neurons, Neto-α controls neurotransmitter release in a KAR-dependent manner. Furthermore, Neto-α is both required and sufficient for the presynaptic increase in neurotransmitter release in response to reduced postsynaptic sensitivity. This KAR-independent function of Neto-α is involved in activity-induced cytomatrix remodeling. We propose that Drosophila ensured NMJ functionality by acquiring two Neto isoforms with differential expression patterns and activities.

Ciba Collection of Medical Illustrations, Volume 3, Part I. Upper Digestive Tract

PEDIATRICS ◽  
1960 ◽  
Vol 25 (2) ◽  
pp. 342-342
Author(s):  
GIULIO J. BARBERO
Keyword(s):  
Human Organism ◽  
High Quality ◽  
Graphic Arts ◽  
Gastrointestinal Physiology ◽  
Form And Function ◽  
Complex Processes ◽  
And Function ◽  
The Relationship ◽  
Upper Gastrointestinal

This volume of the magnificent series of the major anatomy and pathology of the systems of the human organism illustrated by Dr. Netter is a fine example of the high quality of this series. The illustrations are beautifully reproduced with great clarity. The drawings attempt the difficult task of illustration of the relationship between form and function and succeed well in graphically portraying present concepts of upper gastrointestinal physiology. The charts on mastication, vomiting, hunger and deglutition are particularly excellent examples of the graphic arts in the explanation of such complex processes. The text accompanying the illustrations is succinct, precise and well written.

scholarly journals WORK PROGRAM OF MADRASAH COMMITTEE

2020 ◽  
Vol 11 (2) ◽  
pp. 256-264
Author(s):  
Isnaini Septemiarti ◽  
Widia Yunita
Keyword(s):  
Descriptive Study ◽  
Work Program ◽  
Qualitative Descriptive ◽  
And Function ◽  
The Relationship ◽  
Role And Function ◽  
Academic Year

This study aims to determine the role of the madrasah committee in improving the quality of madrasah. This research is a qualitative descriptive study. The subjects in this study were the head of the madrasah and the madrasah committee. While the object of this research is the work program of the MTsN 2 Siak madrasah committee for the 2018/2019 academic year. The number of samples in this study were 13 people consisting of 1 madrasah principal and 12 madrasah committees. Data obtained through interviews, observation, and documentation. The results showed that the madrasah committee had played its role and function as a provider of consideration, support and mediator. In the relationship between the head of madrasah and the madrasah committee, it can be linked as coordinative, supportive, evaluative, normative, collaborative, and communicative.

scholarly journals Talking at cross-purposes?: the effect of gender on New Zealand primary schoolchildren's interaction strategies in pair discussions

2021 ◽  
Author(s):  
◽  
Maria Stubbe
Keyword(s):  
Sex Differences ◽  
New Zealand ◽  
Important Variable ◽  
Point Of View ◽  
Peer Discussion ◽  
And Function ◽  
Task Oriented ◽  
The Relationship ◽  
Qualitative Analyses

<p>This thesis explores one aspect of the relationship between sex and language. Twenty pairs of eleven and twelve year old children were tape-recorded during two discussion tasks. Quantitative and qualitative analyses of the data were carried out to investigate to what extent previously reported sex differences in interactional style could be observed in this group of New Zealand school children. Particular attention was paid to the relationship between such differences and the way in which children learn through talk in peer discussion. Two general hypotheses were tested: (i) that girls would tend to use a more collaborative, polite, and affiliative style of interaction, while boys would tend to use a more competitive, task-oriented style, paying less attention to the processes of interaction, and (ii) that the style of interaction associated with females would be more conducive to effective discussion from a pedagogical point of view. There were no significant sex differences in the use of interruptive forms and overlaps. However, the girls produced more talk relative to the boys in the mixed-sex context, supportive minimal responses were distributed differently, suggesting different norms as to their use and function, and there was a marked sex difference in the use of strategies for expressing disagreement: the boys were over four times more likely than the girls to produce bald, unmodified disagreements (approximately half of their total disagreement responses), while over 90% of the girls' disagreement responses were qualified in some way. These differences in style were linked to the results of the qualitative analysis of the data which provided clear evidence that the sex composition of the dyads was an important variable in determining the overall quality of discussion, with the girls more likely to facilitate effective, open-ended, elaborated discussion than the boys.</p>

scholarly journals Talking at cross-purposes?: the effect of gender on New Zealand primary schoolchildren's interaction strategies in pair discussions

2021 ◽  
Author(s):  
◽  
Maria Stubbe
Keyword(s):  
Sex Differences ◽  
New Zealand ◽  
Important Variable ◽  
Point Of View ◽  
Peer Discussion ◽  
And Function ◽  
Task Oriented ◽  
The Relationship ◽  
Qualitative Analyses

<p>This thesis explores one aspect of the relationship between sex and language. Twenty pairs of eleven and twelve year old children were tape-recorded during two discussion tasks. Quantitative and qualitative analyses of the data were carried out to investigate to what extent previously reported sex differences in interactional style could be observed in this group of New Zealand school children. Particular attention was paid to the relationship between such differences and the way in which children learn through talk in peer discussion. Two general hypotheses were tested: (i) that girls would tend to use a more collaborative, polite, and affiliative style of interaction, while boys would tend to use a more competitive, task-oriented style, paying less attention to the processes of interaction, and (ii) that the style of interaction associated with females would be more conducive to effective discussion from a pedagogical point of view. There were no significant sex differences in the use of interruptive forms and overlaps. However, the girls produced more talk relative to the boys in the mixed-sex context, supportive minimal responses were distributed differently, suggesting different norms as to their use and function, and there was a marked sex difference in the use of strategies for expressing disagreement: the boys were over four times more likely than the girls to produce bald, unmodified disagreements (approximately half of their total disagreement responses), while over 90% of the girls' disagreement responses were qualified in some way. These differences in style were linked to the results of the qualitative analysis of the data which provided clear evidence that the sex composition of the dyads was an important variable in determining the overall quality of discussion, with the girls more likely to facilitate effective, open-ended, elaborated discussion than the boys.</p>

Mechanisms Regulating Neuromuscular Junction Development and Function and Causes of Muscle Wasting

2015 ◽  
Vol 95 (3) ◽  
pp. 809-852 ◽  
Author(s):  
Lionel A. Tintignac ◽  
Hans-Rudolf Brenner ◽  
Markus A. Rüegg
Keyword(s):  
Neuromuscular Junction ◽  
Muscle Mass ◽  
Motor Neurons ◽  
Structural Changes ◽  
Muscle Wasting ◽  
Chemical Synapse ◽  
Neuromuscular Activity ◽  
Medical Need ◽  
Metabolic Properties ◽  
And Function

The neuromuscular junction is the chemical synapse between motor neurons and skeletal muscle fibers. It is designed to reliably convert the action potential from the presynaptic motor neuron into the contraction of the postsynaptic muscle fiber. Diseases that affect the neuromuscular junction may cause failure of this conversion and result in loss of ambulation and respiration. The loss of motor input also causes muscle wasting as muscle mass is constantly adapted to contractile needs by the balancing of protein synthesis and protein degradation. Finally, neuromuscular activity and muscle mass have a major impact on metabolic properties of the organisms. This review discusses the mechanisms involved in the development and maintenance of the neuromuscular junction, the consequences of and the mechanisms involved in its dysfunction, and its role in maintaining muscle mass during aging. As life expectancy is increasing, loss of muscle mass during aging, called sarcopenia, has emerged as a field of high medical need. Interestingly, aging is also accompanied by structural changes at the neuromuscular junction, suggesting that the mechanisms involved in neuromuscular junction maintenance might be disturbed during aging. In addition, there is now evidence that behavioral paradigms and signaling pathways that are involved in longevity also affect neuromuscular junction stability and sarcopenia.

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