Macrophages reside in the muscle spindle to control sensorimotor function at millisecond timescale DOI Creative Commons
Simone Di Giovanni, Yuyang Yan, Irene Vargas

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 11, 2023

Abstract The stretch reflex is a fundamental component of the motor system that orchestrates coordinated muscle contractions underlying movement. At heart this process lie spindles (MS), specialized receptors finely attuned to fluctuations in tension within intrafusal fibers. variation MS triggers series neuronal events; an initial depolarization sensory type Ia afferents subsequently causes activation motoneurons spinal cord. This cascade culminates execution contraction, underscoring presumed closed-loop mechanism between musculoskeletal and nervous systems. In contrast, surprisingly here we report discovery new population macrophages with exclusive molecular functional signatures spindle express machinery for synthesizing releasing glutamate. Using mouse intersectional genetics optogenetics electrophysiology, show (MSMP) drives proprioceptive neuron firing at millisecond timescale. activates circuits, neurons, muscles via glutamate-dependent mechanism. Additionally, found MSMP can also respond circuitry by increasing expression glutaminase, enabling them convert glutamine released myocytes during contraction into Our results have identified cellular component, MSMP, directly regulates neural activity contraction. glutamate-mediated signalling their dynamic response cues introduces novel dimension our understanding sensation action, potentially offering innovative therapeutic approaches conditions affect sensorimotor function.

Language: Английский

Molecular characterization of the intact mouse muscle spindle using a multi-omics approach DOI Creative Commons
Bavat Bornstein, Lia Heinemann‐Yerushalmi,

Sharon Krief

et al.

eLife, Journal Year: 2023, Volume and Issue: 12

Published: Feb. 6, 2023

The proprioceptive system is essential for the control of coordinated movement, posture, and skeletal integrity. sense proprioception produced in brain using peripheral sensory input from receptors such as muscle spindle, which detects changes length muscles. Despite its importance, molecular composition spindle largely unknown. In this study, we generated comprehensive transcriptomic proteomic datasets entire isolated murine deep masseter muscle. We then associated differentially expressed genes with various tissues composing bioinformatic analysis. Immunostaining verified these predictions, thus establishing new markers different tissues. Utilizing markers, identified differentiation stages capsule cells undergo during development. Together, findings provide characterization intact well tools to study development function health disease.

Language: Английский

Citations

14
Muscle spindle afferent neurons preferentially degenerate with aging DOI

Minako Kawai‐Takaishi,

Tohru Hosoyama

Published: May 2, 2025

Abstract Muscle spindles sense changes inmuscle length and transmit them to the central nervous system. Proprioception is essential for gait postural maintenance, abnormality of which has been linked disorders risk falling in older adults. However, effects aging on muscle spindle structure remain nebulous. This study investigated age-related structural themuscle (from equator polar) soleus extensor digitorum longus (EDL) muscles young, middle-aged, aged mice. The findings indicated that shape annulospiral endings sensory neurons began deteriorate middle-aged compared with young mice was further exacerbated These were particularly pronounced nuclear bag fibers, whereas no significant observed intrafusal fibers or capsules. A decline function due weight-bearing weight-shifting also observed, suggesting deterioration proprioceptive innervate fiber responsible dynamic sensitivity prevents proper coordinated movement contributes animals including humans, together functional extrafusal fibers.

Language: Английский

Citations

0
Should We Void Lactate in the Pathophysiology of Delayed Onset Muscle Soreness? Not So Fast! Let’s See a Neurocentric View! DOI Creative Commons
Balázs Sonkodi

Metabolites, Journal Year: 2022, Volume and Issue: 12(9), P. 857 - 857

Published: Sept. 13, 2022

The pathophysiology of delayed onset muscle soreness is not entirely known. It seems to be a simple, exercise-induced pain condition, but has remained mystery for over 120 years. buildup lactic acid used blamed fatigue and soreness; however, studies in the 1980s largely refuted role lactate soreness. Regardless, this belief widely held even today, only general public, within medical scientific community as well. Current opinion highlighting lactate's soreness, if neural dimension neuro-energetics are overlooked. By doing so, have an essential initiation primary damage phase intrafusal space. Unaccustomed or strenuous eccentric contractions suggested facilitate nourishment proprioceptive sensory neurons spindle under hyperexcitation. However, excessive acidosis could eventually contribute impaired proprioception increased nociception pathological condition. Furthermore, also secondary extrafusal space, primarily by potentiating bradykinin. After all, interpretation may help us dispel 40-year-old controversy about

Language: Английский

Citations

18
The coordination of chewing DOI Creative Commons

Dominic Falardeau,

S. Dubois,

Arlette Kolta

et al.

Current Opinion in Neurobiology, Journal Year: 2023, Volume and Issue: 83, P. 102805 - 102805

Published: Oct. 31, 2023

Feeding behavior involves a complex organization of neural circuitry and interconnected pathways between the cortex, brainstem, muscles. Elevated synchronicity is required starting from moment animal brings food to its mouth, chews, initiates subsequent swallowing. Moreover, orofacial sensory motor systems are coordinated in way optimize movement patterns as result integrating information premotor neurons. Recent studies have uncovered significant discoveries employing various creative techniques order identify key components these vital functions. Here, we attempt provide brief overview our current knowledge on systems. While focus will be recent breakthroughs regarding masticatory machinery, also explore how it sometimes intertwined with other functions, such swallowing limb movement.

Language: Английский

Citations

10
Functional specialisation and coordination of myonuclei DOI
Amaury Korb, Shahragim Tajbakhsh, Glenda Comai

et al.

Biological reviews/Biological reviews of the Cambridge Philosophical Society, Journal Year: 2024, Volume and Issue: 99(4), P. 1164 - 1195

Published: March 13, 2024

ABSTRACT Myofibres serve as the functional unit for locomotion, with sarcomere fundamental subunit. Running entire length of this structure are hundreds myonuclei, located at periphery myofibre, juxtaposed to plasma membrane. Myonuclear specialisation and clustering centre ends fibre known be essential muscle contraction, yet molecular basis regionalisation has remained unclear. While ‘myonuclear domain hypothesis’ helped explain how myonuclei can independently govern large cytoplasmic territories, novel technologies have provided granularity on diverse transcriptional programs running simultaneously within syncytia added a new perspective communicate. Building upon this, we explore critical cellular sources heterogeneity myofibres, discussing impact intrinsic extrinsic factors myonuclear programs. This knowledge provides insights understanding development, repair, disease, but also opens avenues development precise therapeutic approaches.

Language: Английский

Citations

3
Macrophages excite muscle spindles with glutamate to bolster locomotion DOI Creative Commons
Yuyang Yan,

Nuria Antolin,

Luming Zhou

et al.

Nature, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 4, 2024

Language: Английский

Citations

3
The mechanosensitive ion channel ASIC2 mediates both proprioceptive sensing and spinal alignment DOI Creative Commons
Bavat Bornstein,

Bridgette Watkins,

Fabian S. Passini

et al.

Experimental Physiology, Journal Year: 2023, Volume and Issue: 109(1), P. 135 - 147

Published: March 23, 2023

Abstract By translating mechanical forces into molecular signals, proprioceptive neurons provide the CNS with information on muscle length and tension, which is necessary to control posture movement. However, identities of players that mediate sensing are largely unknown. Here, we confirm expression mechanosensitive ion channel ASIC2 in sensory neurons. combining vivo proprioception‐related functional tests ex electrophysiological analyses spindles, showed mice lacking Asic2 display impairments spindle responses stretch motor coordination tasks. Finally, analysis skeletons loss‐of‐function revealed a specific effect spinal alignment. Overall, identify as key component regulator spine

Language: Английский

Citations

7
How Can Proteomics Help to Elucidate the Pathophysiological Crosstalk in Muscular Dystrophy and Associated Multi-System Dysfunction? DOI Creative Commons
Paul Dowling, Capucine Trollet, Elisa Négroni

et al.

Proteomes, Journal Year: 2024, Volume and Issue: 12(1), P. 4 - 4

Published: Jan. 16, 2024

This perspective article is concerned with the question of how proteomics, which a core technique systems biology that deeply embedded in multi-omics field modern bioresearch, can help us better understand molecular pathogenesis complex diseases. As an illustrative example monogenetic disorder primarily affects neuromuscular system but characterized by plethora multi-system pathophysiological alterations, muscle-wasting disease Duchenne muscular dystrophy was examined. Recent achievements dystrophinopathy research are described special reference to proteome-wide complexity changes and body-wide alterations/adaptations. Based on description current applications top-down versus bottom-up proteomic approaches their technical challenges, future biological outlined. The envisaged holistic integromic bioanalysis would encompass integration diverse omics-type studies including inter- intra-proteomics as disciplines for systematic protein evaluations, sophisticated biomolecular analyses, physiology, biology, biochemistry histochemistry. Integrated findings promise be instrumental improving our detailed knowledge pathogenic mechanisms dysfunction, widening available biomarker signature improved diagnostic/prognostic procedures, advancing identification novel therapeutic targets treat dystrophy.

Language: Английский

Citations

2
Mass Spectrometry-Based Proteomic Technology and Its Application to Study Skeletal Muscle Cell Biology DOI Creative Commons
Paul Dowling, Dieter Swandulla, Kay Ohlendieck

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(21), P. 2560 - 2560

Published: Nov. 1, 2023

Voluntary striated muscles are characterized by a highly complex and dynamic proteome that efficiently adapts to changed physiological demands or alters considerably during pathophysiological dysfunction. The skeletal muscle has been extensively studied in relation myogenesis, fiber type specification, transitions, the effects of physical exercise, disuse atrophy, neuromuscular disorders, co-morbidities sarcopenia old age. Since tissue accounts for approximately 40% body mass humans, alterations have considerable influence on whole-body physiology. This review outlines main bioanalytical avenues taken proteomic characterization tissues, including top-down proteomics focusing intact proteoforms their post-translational modifications, bottom-up proteomics, which is peptide-centric method concerned with large-scale detection proteins mixtures, subproteomics examines protein composition distinct subcellular fractions. Mass spectrometric studies over last two decades decisively improved our general cell biological understanding diversity heterogeneous individual myofibers muscles. detailed knowledge can now be integrated findings from other omics-type methodologies establish systems view function.

Language: Английский

Citations

6
Degeneration of muscle spindles in a murine model of Pompe disease DOI Creative Commons

Bridgette Watkins,

Jürgen Schultheiß,

Andi Rafuna

et al.

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: April 21, 2023

Abstract Pompe disease is a debilitating medical condition caused by functional deficiency of lysosomal acid alpha-glucosidase (GAA). In addition to muscle weakness, people living with experience motor coordination deficits including an instable gait and posture. We reasoned that impaired spindle function might contribute these deficiencies therefore analyzed proprioception as well structure in 4- 8-month-old Gaa −/− mice. Gait analyses showed reduced inter-limb inter-paw Electrophysiological single-unit proprioceptive afferents revealed sensitivity the dynamic static component stretch response. Finally, progressive degeneration sensory neuron intrafusal fibers was detectable observed increased abundance size lysosomes, fragmentation inner outer connective tissue capsule buildup autophagic vacuoles spindles from mice, indicating defects autophagocytosis. These results demonstrate structural altered Similar changes could patients disease.

Language: Английский

Citations

4