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Genetic background and aging-driven neuroimmune and disc changes underscore herniation susceptibility and pain-associated behaviors in SM/J mice

ABSTRACT: Genetic background and aging-driven neuroimmune and disc changes underscore herniation susceptibility and pain-associated behaviors in SM/J mice

PROVIDER: PRJNA1060319 | ENA |

REPOSITORIES: ENA

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Genetic background and aging-driven neuroimmune and disc changes underscore herniation susceptibility and pain-associated behaviors in SM/J mice

Project description:SM/J mice experience spontaneous age-associated intervertebral disc herniations, with molecular analyses indicating a dysregulated immune system may contribute to this disc pathology. To investigate this, we analyzed the circulating immune cells of these mice during aging, in relation to BL/6 mice, which do not experience disc herniation.

2025-04-30 | GSE252474 | GEO

Genetic background and aging-driven neuroimmune and disc changes underscore herniation susceptibility and pain-associated behaviors in SM/J mice

Project description:There are no appropriate mouse models to study the pathophysiology of spontaneous disc herniations in a wild-type setting. We demonstrate that SM/J mice show a high incidence of age-associated lumbar disc herniations with neurovascular innervations. Transcriptomic comparisons of the SM/J annulus fibrosus with human tissues showed shared pathways related to immune cell activation and inflammation. Notably, aged SM/J mice showed increased pain sensitization and neuroinflammation with altered ECM regulation in the DRG and spinal cord. There were increased T cells in the vertebral marrow, and CyTOF analysis showed increased splenic CD8+ T cells, nonspecific activation of CD8+ memory T cells, and enhanced IFN-γ production in the myeloid compartment. ScRNA-seq of PBMCs showed more B cells, with lower proportions of T cells, monocytes, and granulocytes. This study highlights the contribution of genetic background and aging to increased susceptibility of spontaneous disc herniations and clinically relevant pain phenotypes in SM/J mice.

2025-01-23 | GSE252383 | GEO

Genetic background and aging-driven neuroimmune and disc changes underscore herniation susceptibility and pain-associated behaviors in SM/J mice

Project description:Genetic background and aging-driven neuroimmune and disc changes underscore herniation susceptibility and pain-associated behaviors in SM/J mice

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TMT-based proteomic analysis of CSF in dogs with intervertebral disc herniation

Project description:In our study, MS-based high-resolution proteomic analysis of CSF have been employed in order to gain deeper insights into changes occurring during IVDH in dogs, monitoring the pathophysiological processes at the protein and metabolite levels. The proteomics study involved canine patients classified within two groups. Healthy dogs (control group) (N=6) were mix breeds (20 kg average body weight), age 2-6 years, while the intervertebral disc herniation group (N=9) were mixed breeds (body weight 6-15 kg), age 7-12 years. In IVDH dogs, disc herniation was detected in T13/L1/L2 discs by CT. The dogs in IVDH group were paraplegic with preserved deep pain reflex and underwent a surgery procedure for decompression of the spinal cord.

2021-11-25 | PXD024921 | Pride

SM/J mice display spontaneous early onset disc degeneration link to ion transport system and matrisome changes

Project description:To fully apprehend the complex mechanisms responsible for intervertebral disc (IVD) degeneration, one needs to gain a deeper understanding of what characterizes a good and bad intervertebral disc. Using a quantitative proteomic approach, we compared methodically the differences existing between a mouse model known as good healer LG/J to another mouse model characterize as bad healer SM/J. A total of 5245 proteins were identified. By assessing the overlap of the NP LG/J and SM/J proteomic signature with a list of over 1000 matrisomal proteins generated by Naba and co-workers (33), we provide a first comprehensive comparison of NP IVD matrix composition in a good and bad condition and identify potential changes that are fundamental for maintenance of a healthy disc.

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Multi-Omics Approach to Elucidate Cerebrospinal Fluid Changes in Dogs with Intervertebral Disc Herniation

Project description:Herniation of the intervertebral disc (IVDH) is the most common cause of neurological and intervertebral disc degeneration-related diseases. Since the disc starts to degenerate before it can be observed by currently available diagnostic methods, there is an urgent need for novel diagnostic approaches. To identify molecular networks and pathways which may play important roles in intervertebral disc herniation, as well as to reveal the potential features which could be useful for monitoring disease progression and prognosis, multi-omics profiling including high-resolution LC-MS-based metabolomics and proteomics was performed. Furthermore, multi-omics data were integrated to decipher a complex interaction between individual omic layers leading to improved prediction model. Together with metabolic pathways related to amino acids and lipid metabolism, and coagulation cascades, our integromics prediction model identified the key features in IVDH, namely the proteins FSTL1, SCG5, NUCB1 and CRSP2 and the metabolites N-acetyl-D-glucosamine and adenine, involved in neuropathic pain, myelination, neurotransmission and inflammatory response, respectively. Their clinical application is to be further investigated. The utilization of novel integrative interdisciplinary strategy may provide opportunities to apply the innovative diagnostic and monitoring methods for degenerative spinal disorders.

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2021-08-05 | GSE135270 | GEO

RIP-seq analysis of eukaryotic Sm proteins identifies three major categories of Sm-containing ribonucleoproteins

Project description:Background: Sm proteins are multimeric RNA-binding factors, found in all three domains of life. Eukaryotic Sm proteins, together with their associated RNAs, form small ribonucleoprotein (RNP) complexes important in multiple aspects of gene regulation. Comprehensive knowledge of the RNA components of Sm RNPs is critical for understanding their functions. Results: We developed a multi-targeting RNA-immunoprecipitation sequencing (RIP-seq) strategy to reliably identify Sm-associated RNAs from Drosophila ovaries and cultured human cells. Using this method, we discovered three major categories of Sm-associated transcripts: small nuclear (sn)RNAs, small Cajal body (sca)RNAs and mRNAs. Additional RIP-PCR analysis showed both ubiquitous and tissue-specific interactions. We provide evidence that the mRNA-Sm interactions are mediated by snRNPs, and that one of the mechanisms of interaction is via base pairing. Moreover, the Sm-associated mRNAs are mature, indicating a splicing-independent function for Sm RNPs. Conclusions: This study represents the first comprehensive analysis of eukaryotic Sm-containing RNPs, and provides a basis for additional functional analyses of Sm proteins and their associated snRNPs outside of the context of pre-mRNA splicing. Our findings expand the repertoire of eukaryotic Sm-containing RNPs and suggest new functions for snRNPs in mRNA metabolism.

2013-12-01 | GSE35842 | GEO

Reactive Oxygen Species promote Pyroptosis of Nucleus Pulposus Cells in Modic changes with disc herniation based on smart-RNA sequencing

Project description:Reactive Oxygen Species promote Pyroptosis of Nucleus Pulposus Cells in Modic changes with disc herniation based on smart-RNA sequencing

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