Origin, identity, and function of terminal Schwann cells

Trends in Neurosciences, Год журнала: 2024, Номер 47(6), С. 432 - 446

Опубликована: Апрель 24, 2024

Язык: Английский

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Cellular and molecular evidence that synaptic Schwann cells contribute to aging of mouse neuromuscular junctions

Aging Cell, Год журнала: 2023, Номер 22(11)

Опубликована: Сен. 28, 2023

Abstract Age‐induced degeneration of the neuromuscular junction (NMJ) is associated with motor dysfunction and muscle atrophy. While impact aging on NMJ presynapse postsynapse well‐documented, little known about changes perisynaptic Schwann cells (PSCs), synaptic glia NMJ, undergo during aging. Here, we examined PSCs in young, middle‐aged, old mice three muscles different susceptibility to Using light electron microscopy, found that acquire age‐associated cellular features either prior or at same time as onset degeneration. Notably, aged fail completely cap even though they are more abundant compared young mice. We also form processes intrude into cleft guide axonal sprouts innervate other NMJs. next profiled transcriptome (SCs) identify mechanisms altered PSCs. This analysis revealed a transcriptional pattern previously shown promote phagocytosis absent SCs. It showed upregulate unique pro‐inflammatory molecules Interestingly, neither synaptogenesis genes nor typically upregulated by repair SCs were induced These findings provide insights molecular could be targeted stave off deleterious effects

Язык: Английский

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Cellular and molecular alterations to muscles and neuromuscular synapses in a mouse model of MEGF10-related myopathy

Skeletal Muscle, Год журнала: 2024, Номер 14(1)

Опубликована: Май 17, 2024

Loss-of-function mutations in MEGF10 lead to a rare and understudied neuromuscular disorder known as MEGF10-related myopathy. There are no treatments for the progressive respiratory distress, motor impairment, structural abnormalities muscles caused by loss of function. In this study, we deployed cellular molecular assays obtain additional insights about myopathy juvenile, young adult, middle-aged Megf10 knockout (KO) mice. We found fewer muscle fibers juvenile adult KO mice, supporting published studies that regulates myogenesis affecting satellite cell differentiation. Interestingly, do not exhibit morphological hallmarks atrophy either or next examined junction (NMJ), which has been shown concentrate postnatally, using light electron microscopy. early degenerative features at NMJs mice include increased postsynaptic fragmentation presynaptic regions apposed nicotinic acetylcholine receptors. also perisynaptic Schwann cells intruding into NMJ synaptic cleft. These findings strongly suggest is site postnatal pathology support these observations, RNA-seq analysis revealed genes pathways associated with myogenesis, skeletal health, stability dysregulated compared wild-type Altogether, data provide new valuable

Язык: Английский

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Functional and Structural Changes in Diaphragm Neuromuscular Junctions in Early Aging

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(16), С. 8959 - 8959

Опубликована: Авг. 17, 2024

Age-related impairment of the diaphragm causes respiratory complications. Neuromuscular junction (NMJ) dysfunction can be one triggering events in weaknesses old age. Prominent structural and functional alterations NMJs were described elderly rodents, but NMJ changes middle age remain unclear. Here, we compared muscles from young adult (3 months) middle-aged (12 BALB/c mice. Microelectrode recordings, immunofluorescent staining, electron microscopy, myography, whole-body plethysmography used. We revealed presynaptic (i) postsynaptic (ii) changes. The former included an increase both action potential propagation velocity neurotransmitter release evoked by low-, moderate-, high-frequency activity a decrease immunoexpression synapsin 1 synaptic vesicle clustering. latter consisted currents via nicotinic acetylcholine receptors area their distribution. These correlated with increased contractile responses to moderate- nerve activation. Additionally, found pattern respiration (an peak inspiratory flow tendency elevation tidal volume), which imply conclude that enhancement neuromuscular communication (due mechanism) accompanied improved occurs early aging.

Язык: Английский

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Impact of Ageing and Disuse on Neuromuscular Junction and Mitochondrial Function and Morphology: Current Evidence and Controversies

Ageing Research Reviews, Год журнала: 2024, Номер unknown, С. 102586 - 102586

Опубликована: Ноя. 1, 2024

Язык: Английский

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Loss of MEGF10 Decreases the Number of Perisynaptic Schwann Cells and Innervation of Neuromuscular Junctions in Aging Mice

Journal of the Peripheral Nervous System, Год журнала: 2025, Номер 30(1)

Опубликована: Март 1, 2025

ABSTRACT Background and Aims At the neuromuscular junction (NMJ), synapse between motor neurons muscle fibers, reside perisynaptic Schwann cells (PSCs) which are specialized glia that regulate maintenance repair of this synapse. While we know how PSC morphology numbers change in aging various disorders adversely affect NMJ, molecular mechanisms alter functions remain unknown. In study, investigated whether MEGF10 PSCs modulates NMJ stability developing, healthy young adult, middle‐aged, axotomized mice. is a glial phagocytic receptor enriched compared to other (SCs). Methods We isolated from transgenic reporter mouse line assess Megf10 expression at different ages following nerve injury using qPCR. then used conditional lacking all SCs, including ( SC‐KO mice). examined NMJs axonal debris clearance mice confocal microscopy. Results found peaks during development decreases denervation NMJs. were morphologically normal developing adult This was not case middle‐aged mice, presented with fewer PSCs, decreased coverage endplate, innervation comparison control Following injury‐induced damage, cleared faster mice; yet, rate reinnervation unchanged Interpretation The data study suggest maintain number aging. also suggests important roles for mediating injury.

Язык: Английский

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Integrating Postsynaptic Morphology and Dynamics to Evaluate Neuromuscular Synapse Status: Insights from α-bungarotoxin.

Toxicon, Год журнала: 2025, Номер 262, С. 108404 - 108404

Опубликована: Май 10, 2025

Язык: Английский

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Comprehensive characterization and validation of the Prp-hPFN1G118V mouse model: Guidelines for preclinical therapeutic testing for ALS

Neurobiology of Disease, Год журнала: 2025, Номер unknown, С. 106975 - 106975

Опубликована: Июнь 1, 2025

The hPFN1G118V mouse model, overexpressing mutant human profilin1 linked to a rare form of ALS, was comprehensively characterized assess its suitability for preclinical drug testing. Using large cohort nearly 250 transgenic and wild-type mice in longitudinal study, we combined behavioral, electrophysiological, neuropathological assessments define the chronology pathological events inherent subject variability. early stage disease this model by elevated plasma neurofilament light chain levels, an effect that persisted progressed throughout course disease, followed spinal cord neuroinflammation, suggesting axonal pathology is initiating event. middle involved progressive neuromuscular decline, including reductions compound muscle action potential (CMAP) grip strength, accompanied junction degeneration. end-stage onset visible changes such as weight loss, gait abnormalities hindlimb paresis quickly paralysis. At also observed motor neuron loss TDP-43 pathology. average humane endpoint 213 days females 237 males. Our findings demonstrate recapitulate key ALS features with moderate progression reproducible course, making them valuable therapeutic Recommendations are provided optimize study design testing, emphasizing survival duration primary endpoint, CMAP NFL secondary readouts.

Язык: Английский

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Muscle aging and sarcopenia: The pathology, etiology, and most promising therapeutic targets

Molecular Aspects of Medicine, Год журнала: 2024, Номер 100, С. 101319 - 101319

Опубликована: Сен. 23, 2024

Язык: Английский

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Differential evaluation of neuromuscular injuries to understand re-innervation at the neuromuscular junction

Experimental Neurology, Год журнала: 2024, Номер 382, С. 114996 - 114996

Опубликована: Окт. 10, 2024

Peripheral nerve-crush injury is a well-established model of neuromuscular junction (NMJ) denervation and subsequent re-innervation. Functionally, the skeletal muscle follows similar pattern as neural recovery, with immediate loss force production that steadily improves in parallel rates On other hand, traumatic to itself, specifically volumetric (VML), results an irrecoverable function. Recent work has indicated significant impairments NMJ following this appear chronic nature, alongside lack functional recovery. Thus, goal study was compare effects nerve on remodeling. Even numbers adult male female mice were used three experimental groups: Naïve, crush, VML injury; terminal timepoints: 3-, 48-, 112-days post-injury. Confirming assumed recoverability two models, we found vivo maximal torque fully restored but remained at deficit VML. Compared Naïve injury, aberrantly high trophic signaling (e.g., neuregulin-1) supporting cells, including Schwann cells sub-synaptic nuclei. In some cases, sex differences detected, higher innervation females than males. Both crush display changes morphology, such increased fragmentation sprouting, highlighting potential for modeling regeneration adulthood, established nerve-injury models.

Язык: Английский

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