muscle spindle
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Author(s):  
Philip Barrett ◽  
Tom J. Quick ◽  
Vivek Mudera ◽  
Darren J. Player

Muscle spindles are sensory organs that detect and mediate both static and dynamic muscle stretch and monitor muscle position, through a specialised cell population, termed intrafusal fibres. It is these fibres that provide a key contribution to proprioception and muscle spindle dysfunction is associated with multiple neuromuscular diseases, aging and nerve injuries. To date, there are few publications focussed on de novo generation and characterisation of intrafusal muscle fibres in vitro. To this end, current models of skeletal muscle focus on extrafusal fibres and lack an appreciation for the afferent functions of the muscle spindle. The goal of this study was to produce and define intrafusal bag and chain myotubes from differentiated C2C12 myoblasts, utilising the addition of the developmentally associated protein, Neuregulin 1 (Nrg-1). Intrafusal bag myotubes have a fusiform shape and were assigned using statistical morphological parameters. The model was further validated using immunofluorescent microscopy and western blot analysis, directed against an extensive list of putative intrafusal specific markers, as identified in vivo. The addition of Nrg-1 treatment resulted in a 5-fold increase in intrafusal bag myotubes (as assessed by morphology) and increased protein and gene expression of the intrafusal specific transcription factor, Egr3. Surprisingly, Nrg-1 treated myotubes had significantly reduced gene and protein expression of many intrafusal specific markers and showed no specificity towards intrafusal bag morphology. Another novel finding highlights a proliferative effect for Nrg-1 during the serum starvation-initiated differentiation phase, leading to increased nuclei counts, paired with less myotube area per myonuclei. Therefore, despite no clear collective evidence for specific intrafusal development, Nrg-1 treated myotubes share two inherent characteristics of intrafusal fibres, which contain increased satellite cell numbers and smaller myonuclear domains compared with their extrafusal neighbours. This research represents a minimalistic, monocellular C2C12 model for progression towards de novo intrafusal skeletal muscle generation, with the most extensive characterisation to date. Integration of intrafusal myotubes, characteristic of native, in vivo intrafusal skeletal muscle into future biomimetic tissue engineered models could provide platforms for developmental or disease state studies, pre-clinical screening, or clinical applications.


2021 ◽  
Vol 11 (8) ◽  
pp. 1022
Author(s):  
Carla R. Lima ◽  
Daniel F. Martins ◽  
Snigdhasree Avatapally ◽  
Minjung Cho ◽  
Peng Li ◽  
...  

Objective: To characterize the effect of unilateral (single and two-level) lumbar facet/zygapophysial joint fixation on paraspinal muscle spindle activity immediately following L4 or L6 high velocity low amplitude spinal manipulation (HVLA-SM) delivered at various thrust durations. Methods: Secondary analysis of immediate (≤2 s) post-HVLA-SM trunk muscle spindle response from two studies involving anesthetized adult cats (n = 39; 2.3–6.0 kg) with either a unilateral single (L5/6) or two-level (L5/6 and L6/7) facet joint fixation. All facet fixations were contralateral to L6 dorsal root recordings. HVLA-SM was delivered to the spinous process in a posterior-to-anterior direction using a feedback motor with a peak thrust magnitude of 55% of average cat body weight and thrust durations of 75, 100, 150, and 250 ms. Time to 1st action potential and spindle activity during 1 and 2 s post-HVLA-SM comparisons were made between facet joint fixation conditions and HVLA-SM segmental thrust levels. Results: Neither two-level facet joint fixation, nor HVLA-SM segmental level significantly altered immediate post-HVLA-SM spindle discharge at tested thrust durations (FDR > 0.05). Conclusions: Two-level facet joint fixation failed to alter immediate (≤2 s) post-HVLA-SM spindle discharge when compared to single-level facet joint fixation at any thrust duration. Segmental thrust level did not alter immediate post-HVLA-SM spindle response in two-level facet joint fixation preparations.


Author(s):  
Carla R. Lima ◽  
Randall S. Sozio ◽  
AaMarryah C. Law ◽  
Alicia J. Nelson ◽  
Harshvardhan Singh ◽  
...  
Keyword(s):  

2021 ◽  
Vol 35 (S1) ◽  
Author(s):  
Serena Ortiz ◽  
David Mejia ◽  
Kimberly Than ◽  
Enoch Kim ◽  
Cebrina Navarro ◽  
...  
Keyword(s):  

2021 ◽  
Author(s):  
Kimberly Than ◽  
Enoch Kim ◽  
Cebrina Navarro ◽  
Sarah Chu ◽  
Nikola Klier ◽  
...  

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Katherine M. Oliver ◽  
Danny M. Florez-Paz ◽  
Tudor Constantin Badea ◽  
George Z. Mentis ◽  
Vilas Menon ◽  
...  

AbstractProprioceptive feedback mainly derives from groups Ia and II muscle spindle (MS) afferents and group Ib Golgi tendon organ (GTO) afferents, but the molecular correlates of these three afferent subtypes remain unknown. We performed single cell RNA sequencing of genetically identified adult proprioceptors and uncovered five molecularly distinct neuronal clusters. Validation of cluster-specific transcripts in dorsal root ganglia and skeletal muscle demonstrates that two of these clusters correspond to group Ia MS afferents and group Ib GTO afferent proprioceptors, respectively, and suggest that the remaining clusters could represent group II MS afferents. Lineage analysis between proprioceptor transcriptomes at different developmental stages provides evidence that proprioceptor subtype identities emerge late in development. Together, our data provide comprehensive molecular signatures for groups Ia and II MS afferents and group Ib GTO afferents, enabling genetic interrogation of the role of individual proprioceptor subtypes in regulating motor output.


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