Dermal TRPV1 innervations engage a macrophage- and fibroblast-containing pathway to activate hair growth in mice

Developmental Cell, Год журнала: 2024, Номер unknown

Опубликована: Июнь 1, 2024

Pain, detected by nociceptors, is an integral part of injury, yet whether and how it can impact tissue physiology recovery remain understudied. Here, we applied chemogenetics in mice to locally activate dermal TRPV1 innervations naive skin found that triggered new regenerative cycling dormant hair follicles (HFs). This was preceded rapid apoptosis macrophages, mediated the neuropeptide calcitonin gene-related peptide (CGRP). activation also a macrophage-dependent induction osteopontin (Spp1)-expressing fibroblasts. The CGRP extracellular matrix protein Spp1 were required for nociceptor-triggered growth. Finally, showed epidermal abrasion injury induced Spp1-expressing fibroblasts growth via neuron CGRP-dependent mechanism. Collectively, these data demonstrated role nociceptors orchestrating macrophage fibroblast-supported mechanism promote enabling efficient restoration this mechano- thermo-protective barrier after wounding.

Язык: Английский

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Development of a polyacrylamide/chitosan composite hydrogel conduit containing synergistic cues of elasticity and topographies for promoting peripheral nerve regeneration

Biomaterials Science, Год журнала: 2022, Номер 10(17), С. 4915 - 4932

Опубликована: Янв. 1, 2022

Substrate elasticity and topographical guidance are crucial factors for regulating tissue regeneration, but the synergistic effects of both cues on peripheral nerve regeneration still unclear. In this paper, polyacrylamide/chitosan (PAM/CS) composite hydrogels with characteristics morphology were prepared using in situ free-radical polymerization micro-molding. The physicochemical properties characterized, effect was systematically evaluated via vitro vivo experiments, respectively. experiments showed that a PAM/CS hydrogel an elastic modulus 5.822 kPa/8.41 kPa surface groove width 30 μm, dorsal root ganglion (DRG) neurite had strong growth ability better-oriented status. samples taken from each group at 2 12 weeks after bridging rabbit sciatic defects conduit. General observation body transplanted nerve, electro-physiological examination, muscle wet weight recovery rate detection comparison, frozen section immunofluorescence staining myelinated fiber comparison used to evaluate transplantation. 8.41 μm similar those autograft group. At same time, signaling pathways, including focal adhesion markers vinculin, p-FAK, Rho A protein, referring axon extension, initially revealed. summary, our developed implants containing topographies may provide new effective strategy treatment injury future.

Язык: Английский

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Recent advances in understanding neuronal diversity and neural circuit complexity across different brain regions using single-cell sequencing

Frontiers in Neural Circuits, Год журнала: 2023, Номер 17

Опубликована: Март 30, 2023

Neural circuits are characterized as interconnecting neuron networks connected by synapses. Some kinds of gene expression and/or functional changes neurons and synaptic connections may result in aberrant neural circuits, which has been recognized one crucial pathological mechanism for the onset many neurological diseases. Gradual advances single-cell sequencing approaches with strong technological advantages, exemplified high throughput increased resolution live cells, have enabled it to assist us understanding neuronal diversity across diverse brain regions further transformed our knowledge cellular building blocks through revealing numerous molecular signatures. Currently published transcriptomic studies elucidated various subpopulations well their distribution prefrontal cortex, hippocampus, hypothalamus, dorsal root ganglion, etc. Better characterization region-specific shed light on new mechanisms involved selecting potential targets prevention treatment specific disorders based established roles. Given populations different regions, we aim give a brief sketch current progress circuit complexity according locations. With special focus application sequencing, thereby summarize relevant findings. Considering importance spatial context connectivity also discuss few results obtained transcriptomics. Taken together, these data lay mechanistic basis identification components, links signatures anatomical connectivity, morphology, physiology. Furthermore, comprehensive subtypes, distributions, patterns via is critical properties how they generate region-dependent interactions context.

Язык: Английский

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Schwann cell-secreted PGE2 promotes sensory neuron excitability during development

Cell, Год журнала: 2024, Номер 187(17), С. 4690 - 4712.e30

Опубликована: Авг. 1, 2024

Язык: Английский

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Molecular and Cellular Mechanisms Underlying Peripheral Nerve Injury-Induced Cellular Ecological Shifts: Implications for Neuroregeneration

IBRO Neuroscience Reports, Год журнала: 2024, Номер 18, С. 120 - 129

Опубликована: Дек. 28, 2024

The peripheral nervous system is a complex ecological network, and its injury triggers series of fine-grained intercellular regulations that play crucial role in the repair process. sophisticated initiates cascade intricate regulatory processes are instrumental Despite advent microsurgical techniques, nerve injuries frequently proves inadequate, resulting adverse effects on patients' quality life. Accordingly, continued pursuit more efficacious treatments paramount importance. In this paper, review relevant literature from recent years was conducted to identify key cell types involved after injury. These included Schwann cells, macrophages, neutrophils, endothelial fibroblasts. depth. This paper analyses phenotypic changes these cells injury, factors affecting changes, how they coordinate with neurons other types. addition, it explores potential mechanisms mediate behaviour cells. Understanding interactions between their mutual regulation great significance for discovery new neuroregenerative identification therapeutic targets.

Язык: Английский

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Nociceptors: Their Role in Body’s Defenses, Tissue Specific Variations and Anatomical Update

Journal of Pain Research, Год журнала: 2022, Номер Volume 15, С. 867 - 877

Опубликована: Март 31, 2022

Abstract: The human body is constantly under the influence of numerous pathological factors: both external and internal. These factors can be potentially harmful are perceived as such with a specialized nervous system subunit: nociceptive system. functional unit nociceptor. Recent studies have shown that nociceptors play crucial role in maintaining defensive homeostasis (responsive, immune, behavioral). Nociceptors respond to stimuli within viscera, bones, muscles, skin sensory organs. They function complex predictors harm through formation pain stimulus. Their structures vary different tissues. This variability reflects anatomical peculiarities varying significant adaptive, protective behavioral reactions. capabilities vast spread throughout make them main units body's defense system, allowing us interact inner outer environments. Keywords: nociceptors, homeostasis, tissue specific variability, perception

Язык: Английский

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Nerve–stem cell crosstalk in skin regeneration and diseases

Trends in Molecular Medicine, Год журнала: 2022, Номер 28(7), С. 583 - 595

Опубликована: Май 17, 2022

Язык: Английский

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A role for axon–glial interactions and Netrin-G1 signaling in the formation of low-threshold mechanoreceptor end organs

Proceedings of the National Academy of Sciences, Год журнала: 2022, Номер 119(43)

Опубликована: Окт. 17, 2022

Low-threshold mechanoreceptors (LTMRs) and their cutaneous end organs convert light mechanical forces acting on the skin into electrical signals that propagate to central nervous system. In mouse hairy skin, hair follicle–associated longitudinal lanceolate complexes, which are comprising LTMR axonal endings intimately associate with terminal Schwann cell (TSC) processes, mediate responses deflection indentation. Here, we characterized developmental steps leading formation of Aβ rapidly adapting (RA)-LTMR Aδ-LTMR complexes. During early postnatal development, RA-LTMRs Aδ-LTMRs extend prune branches in close association nascent TSC processes. Netrin-G1 is expressed these developing RA-LTMR endings, Ntng1 ablation experiments indicate functions sensory neurons promote ending elaboration around follicles. The Netrin-G ligand (NGL-1), encoded by Lrrc4c , TSCs, partially phenocopied complex deficits observed mutants. Moreover, NGL-1–Netrin-G1 signaling a general mediator organ across diverse tissue types demonstrated fact associated Meissner corpuscles Pacinian also compromised mutant mice. Thus, axon–glia interactions, mediated part signaling, formation.

Язык: Английский

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Molecular identity of proprioceptor subtypes innervating different muscle groups in mice

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Ноя. 11, 2022

Abstract The precise execution of coordinated movements depends on proprioception, the sense body position in space. However, molecular underpinnings proprioceptive neuron subtype identities are not fully understood. Here we used a single-cell transcriptomic approach to define mouse proprioceptor subtypes according identity muscle they innervate. We identified and validated signatures associated with proprioceptors innervating back ( Tox , Epha3 ), abdominal C1ql2 hindlimb Gabrg1 Efna5 ) muscles. also found that precedes acquisition receptor character comprise programs controlling wiring specificity. These findings indicate muscle-type is fundamental aspect differentiation acquired during early development includes involved control target

Язык: Английский

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Docking protein 6 (DOK6) selectively docks the neurotrophic signaling transduction to restrain peripheral neuropathy

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Фев. 14, 2024

Abstract The appropriate and specific response of nerve cells to various external cues is essential for the establishment maintenance neural circuits, this process requires proper recruitment adaptor molecules selectively activate downstream pathways. Here, we identified that DOK6, a member Dok (downstream tyrosine kinases) family, required peripheral axons, loss Dok6 can cause typical neuropathy symptoms in mice, manifested as impaired sensory, abnormal posture, paw deformities, blocked conduction, dysmyelination. Furthermore, highly expressed neurons but not Schwann cells, genetic deletion led myelin outfolding, axon destruction, hindered retrograde axonal transport. Specifically, DOK6 acts an protein selectivity-mediated neurotrophic signal transduction transport TrkC Ret TrkA TrkB. interacts with certain proteins trafficking machinery controls their phosphorylation, including MAP1B, Tau Dynein transport, specifically activates ERK1/2 kinase pathway maintain survival homeostasis. This finding provides new clues potential insights into pathogenesis treatment hereditary neuropathies other degenerative diseases.

Язык: Английский

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