Molecular characterization of the intact mouse muscle spindle using a multi-omics approach

eLife, Год журнала: 2023, Номер 12

Опубликована: Фев. 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.

Язык: Английский

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Muscle spindle afferent neurons preferentially degenerate with aging

Опубликована: Май 2, 2025

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.

Язык: Английский

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

Metabolites, Год журнала: 2022, Номер 12(9), С. 857 - 857

Опубликована: Сен. 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

Язык: Английский

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The coordination of chewing

Current Opinion in Neurobiology, Год журнала: 2023, Номер 83, С. 102805 - 102805

Опубликована: Окт. 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.

Язык: Английский

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Functional specialisation and coordination of myonuclei

Biological reviews/Biological reviews of the Cambridge Philosophical Society, Год журнала: 2024, Номер 99(4), С. 1164 - 1195

Опубликована: Март 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.

Язык: Английский

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Macrophages excite muscle spindles with glutamate to bolster locomotion

Nature, Год журнала: 2024, Номер unknown

Опубликована: Дек. 4, 2024

Язык: Английский

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The mechanosensitive ion channel ASIC2 mediates both proprioceptive sensing and spinal alignment

Experimental Physiology, Год журнала: 2023, Номер 109(1), С. 135 - 147

Опубликована: Март 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

Язык: Английский

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How Can Proteomics Help to Elucidate the Pathophysiological Crosstalk in Muscular Dystrophy and Associated Multi-System Dysfunction?

Proteomes, Год журнала: 2024, Номер 12(1), С. 4 - 4

Опубликована: Янв. 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.

Язык: Английский

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Mass Spectrometry-Based Proteomic Technology and Its Application to Study Skeletal Muscle Cell Biology

Cells, Год журнала: 2023, Номер 12(21), С. 2560 - 2560

Опубликована: Ноя. 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.

Язык: Английский

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Transcriptional profiling of dental sensory and proprioceptive trigeminal neurons using single-cell RNA sequencing

International Journal of Oral Science, Год журнала: 2023, Номер 15(1)

Опубликована: Сен. 25, 2023

Dental primary afferent (DPA) neurons and proprioceptive mesencephalic trigeminal nucleus (MTN) neurons, located in the ganglion brainstem, respectively, are essential for controlling masticatory functions. Despite extensive transcriptomic studies on various somatosensory there is still a lack of knowledge about molecular identities these populations due to technical challenges their circuit-validated isolation. Here, we employed high-depth single-cell RNA sequencing (scRNA-seq) combination with retrograde tracing mice identify intrinsic transcriptional features DPA MTN neurons. Our transcriptome analysis revealed five major types cell type-specific gene enrichment, some which exhibit unique mechano-nociceptive properties capable transmitting nociception response innocuous mechanical stimuli teeth. Furthermore, discovered cellular heterogeneity within that potentially contribute responsiveness stretch masseter muscle spindles. Additionally, represented sensory compartments distinct profiles characterized by ion channels, receptors, neuropeptides, mechanoreceptors. Together, our study provides new biological insights regarding highly specialized mechanosensory functions pain proprioception.

Язык: Английский

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