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Shock waves induce an evolutionary conserved mechanism of spinal cord regeneration via Toll-like receptor 3

ABSTRACT: Shock waves induce an evolutionary conserved mechanism of spinal cord regeneration via Toll-like receptor 3

PROVIDER: PRJNA628694 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11616276.fastq.gz	Fastqsanger.gz
	SRR11616277.fastq.gz	Fastqsanger.gz
	SRR11616278.fastq.gz	Fastqsanger.gz
	SRR11616279.fastq.gz	Fastqsanger.gz

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Shock waves induce an evolutionary conserved mechanism of spinal cord regeneration via Toll-like receptor 3

Project description:Shock wave therapy (SWT) is improving motor function and decreasing lesion size in wild-type but not Tlr3-/- mice via IL6 dependent differentiation of neuronal progenitor cells. Both SWT and TLR3 stimulation enhance neuronal sprouting and survival, even in human spinal cord cultures. We could also identify tlr3 as a crucial enhancer of spinal cord generation in zebrafish. In order to substantiate underlying mechanisms of the SWT for spinal cords, cultured human neurons (neuroblastoma cell line) were treated with SWT and gene expression profiling were performed by RNAseq.

2020-09-08 | GSE149446 | GEO

Shock waves promote spinal cord repair via TLR3.

Project description:Spinal cord injury (SCI) remains a devastating condition with poor prognosis and very limited treatment options. Affected patients are severely restricted in their daily activities. Shock wave therapy (SWT) has shown potent regenerative properties in bone fractures, wounds, and ischemic myocardium via activation of the innate immune receptor TLR3. Here, we report on the efficacy of SWT for regeneration of SCI. SWT improved motor function and decreased lesion size in WT but not Tlr3-/- mice via inhibition of neuronal degeneration and IL6-dependent recruitment and differentiation of neuronal progenitor cells. Both SWT and TLR3 stimulation enhanced neuronal sprouting and improved neuronal survival, even in human spinal cord cultures. We identified tlr3 as crucial enhancer of spinal cord regeneration in zebrafish. Our findings indicate that TLR3 signaling is involved in neuroprotection and spinal cord repair and suggest that TLR3 stimulation via SWT could become a potent regenerative treatment option.

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Combinatorial therapies for spinal cord injury: strategies to induce regeneration.

Project description: Not available

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Diet, Genes and Colorectal Cancer - With Focus on Toll-like Receptor Polymorphisms

Project description:The aim of this study is to investigate the interaction between diet - primary meat and fiber - and polymorphisms in Toll-like receptors in relation to risk of colorectal cancer in a Danish prospective cohort.

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Impaired Organization of Paired-Pulse TMS-Induced I-Waves After Human Spinal Cord Injury.

Project description:Paired-pulse transcranial magnetic stimulation (TMS) of the human motor cortex results in consecutive facilitatory motor-evoked potential (MEP) peaks in surface electromyography in intact humans. Here, we tested the effect of an incomplete cervical spinal cord injury (SCI) on early (first) and late (second and third) MEP peaks in a resting intrinsic finger muscle. We found that all peaks had decreased amplitude in SCI subjects compared with controls. The second and third peaks were delayed with the third peak also showing an increased duration. The delay of the third peak was smaller than that seen in controls at lower stimulation intensity, suggesting lesser influence of decreased corticospinal inputs. A mathematical model showed that after SCI the third peak aberrantly contributed to spinal motoneurone recruitment, regardless on the motor unit threshold tested. Temporal and spatial aspects of the late peaks correlated with MEP size and hand motor output. Thus, early and late TMS-induced MEP peaks undergo distinct modulation after SCI, with the third peak likely reflecting a decreased ability to summate descending volleys at the spinal level. We argue that the later corticospinal inputs on the spinal cord might be crucial for recruitment of motoneurones after human SCI.

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Expression pattern of Pseudomonas aeruginosa biofilm-residing bacteria exposed to gentamicin or surface acoustic waves or gentamicin and surface acoustic waves combined

Project description:Bacteria are known to respond to various environmental stimuli including nutrient deprivation, osmotic stress, and exposure to antibiotics. Our experimental data showed that P. aeruginosa biofilm formed in urinary catheters is very suseptible to gentamicin treatment when combined with exposure to surface acoustic waves Our goal was to establish whether P. aeruginosa is capable of specifically sensing the surface acoustic waves as well as to try and decipher the molecular mechanism underlying the increased biofilm suseptibility to antibiotics treatment

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Formation of polarized contractile interfaces by self-organized Toll-8/Cirl GPCR asymmetry

Project description:Tissue morphogenesis requires the spatial control over actomyosin contractility to drive cell shape changes. How developmental patterning information controls cell mechanics is poorly understood. In the Drosophila embryo ectoderm, Myosin-II is enriched at the interface between antero-posterior neighboring cells, leading to planar polarized cell intercalation. G protein-coupled receptors (GPCRs) are required for planar polarized Myosin-II activation at junctions and Toll receptors provide a positional code underlying this process. How Toll receptors polarize actomyosin contractility remains unknown. Here we report that cells expressing different levels of a single Toll receptor Toll-8 activate Myosin-II at their interface. Surprisingly, the Toll-8 intracellular domain is not required for signaling at cell interfaces suggesting signaling by proxy. We found that Toll-8 forms a molecular complex with the adhesion GPCR Cirl/Latrophilin that is required for Toll-8 dependent junctional Myosin-II activation. Strikingly, the interfaces between Cirl expressing and cirl mutant cells also activate Myosin-II suggesting that Toll-8 induces Cirl asymmetric signaling at cell interfaces. We further showed that Toll-8 recruits Cirl both in trans and in cis, inducing asymmetric Cirl localization at the boundary of the Toll-8 expression domain. Finally, we found that Toll-8 and Cirl exhibit dynamic interdependent planar polarization when neighboring cells express different levels of Toll-8. Through this feedback, Toll-8 and Cirl self-organize planar polarized signaling.

2021-04-22 | PXD017895 | Pride

Purinergic junctional transmission and propagation of calcium waves in cultured spinal cord microglial networks.

Project description:In order to elucidate the mechanisms of purinergic transmission of calcium (Ca(2 + )) waves between microglial cells, we have employed micro-photolithographic methods to form discrete patterns of microglia that allow quantitative measurements of Ca(2 + ) wave propagation. Microglia were confined to lanes 20-100 [Formula: see text] wide and Ca(2 + ) waves propagated from a point of mechanical stimulation, with a diminution in amplitude, for about 120 [Formula: see text]. The number of cells participating in propagation also decreased over this distance. Ca(2 + ) waves could propagate across a cell-free lane from one microglia lane to another if this distance of separation was less than about 60 [Formula: see text], indicating that propagation involved diffusion of a chemical transmitter. This transmitter was identified as ATP since all Ca(2 + ) wave propagation was blocked by the purinoceptor antagonist suramin, which blocks P2Y(2) and P2Y(12) at relatively low concentrations. Antibodies to P2Y(12) showed these at very high density compared with P2Y(2), indicating a role for P2Y(12) receptors. These observations were quantitatively accounted for by a model in which the main determinants are the diffusion of ATP released from a stimulated microglial cell and differences in the dissociation constant of the purinoceptors on the microglial cells.

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Neuronal Pre- and Postconditioning via Toll-like Receptor 3 Agonist or Extracorporeal Shock Wave Therapy as New Treatment Strategies for Spinal Cord Ischemia: An In Vitro Study.

Project description:Spinal cord ischemia (SCI) is a devastating and unpredictable complication of thoracoabdominal aortic repair. Postischemic Toll-like receptor 3 (TLR3) activation through either direct agonists or shock wave therapy (SWT) has been previously shown to ameliorate damage in SCI models. Whether the same applies for pre- or postconditioning remains unclear. In a model of cultured SHSY-5Y cells, preconditioning with either poly(I:C), a TLR3 agonist, or SWT was performed before induction of hypoxia, whereas postconditioning treatment was performed after termination of hypoxia. We measured cytokine expression via RT-PCR and utilized Western blot analysis for the analysis of signaling and apoptosis. TLR3 activation via poly(I:C) significantly reduced apoptotic markers in both pre- and postconditioning, the former yielding more favorable results through an additional suppression of TLR4 and its downstream signaling. On the contrary, SWT showed slightly more favorable effects in the setting of postconditioning with significantly reduced markers of apoptosis. Pre- and post-ischemic direct TLR3 activation as well as post-ischemic SWT can decrease apoptosis and proinflammatory cytokine expression significantly in vitro and might therefore pose possible new treatment strategies for ischemic spinal cord injury.

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Sequential Waves of Protein Phosphorylation Functionally Rewire the Proteome to Drive Gametogenesis

Project description:Using phosphoproteomics, we show that regulated waves of protein phosphorylation affect virtually all cellular functions to supoort meiotic entry, meiotic progeression and gamete morphogenesis.

2022-12-13 | PXD033675 | Pride

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