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Genetics- and age-driven neuroimmune and disc changes underscore herniation susceptibility and pain-associated behaviors in SM/J mice

2025-04-23Artigo de investigação Acesso aberto
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dc.contributor.authorNovais, Emanuel J.
dc.contributor.authorOttone, Olivia K.
dc.contributor.authorBrown, Eric V.
dc.contributor.authorMadhu, Vedavathi
dc.contributor.authorTran, Victoria A.
dc.contributor.authorRamteke, Pranay
dc.contributor.authorDighe, Abhijit S.
dc.contributor.authorSolga, Michael D.
dc.contributor.authorManchel, Alexandra
dc.contributor.authorLepore, Angelo C.
dc.contributor.authorRisbud, Makarand V.
dc.date.accessioned2025-08-13T15:06:01Z
dc.date.available2025-08-13T15:06:01Z
dc.date.issued2025-04-23
dc.description.abstractThere are no appropriate mouse models to study the pathophysiology of spontaneous disc herniations in a wild-type setting. SM/J mice, a poor healer inbred strain, presented 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 extracellular matrix regulation in the dorsal root ganglia and spinal cord. There were increased T cells in the vertebral marrow, and cytometry by time-of-flight analysis showed increased splenic CD8+ T cells, nonspecific activation of CD8+ memory T cells, and enhanced interferon-γ production in the myeloid compartment. Single-cell RNA sequencing of peripheral blood mononuclear cells 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 intervertebral disc herniations in a clinically relevant murine model.eng
dc.identifier.citationNovais, E. J., Ottone, O. K., Brown, E. V., & Madhu, V. et al. (2025). Genetics- and age-driven neuroimmune and disc changes underscore herniation susceptibility and pain-associated behaviors in SM/J mice. Science advances, 11(17), Article eado6847. https://doi.org/10.1126/sciadv.ado6847
dc.identifier.doi10.1126/sciadv.ado6847
dc.identifier.eid105003551374
dc.identifier.issn2375-2548
dc.identifier.other38e06442-05de-4960-a984-a8f24534bfe0
dc.identifier.pmcPMC12017323
dc.identifier.pmid40267183
dc.identifier.urihttp://hdl.handle.net/10400.14/54555
dc.identifier.wos001473064000017
dc.language.isoeng
dc.peerreviewedyes
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/
dc.titleGenetics- and age-driven neuroimmune and disc changes underscore herniation susceptibility and pain-associated behaviors in SM/J miceeng
dc.typeresearch article
dspace.entity.typePublication
oaire.citation.issue17
oaire.citation.titleScience advances
oaire.citation.volume11
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85

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