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Thread: Neuroinflammatory signals drive Scoliosis in Zebrafish model

  1. #1
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    Neuroinflammatory signals drive Scoliosis in Zebrafish model

    Neuroinflammatory signals drive spinal curve formation in zebrafish models of idiopathic scoliosis.

    December 12, 2018

    The etiopathogenesis of idiopathic scoliosis (IS), a highly prevalent spinal deformity that occurs in the absence of obvious congenital or physiological abnormalities, is poorly understood. Although recent zebrafish genetic studies have linked cilia motility and cerebrospinal fluid (CSF) flow defects with scoliosis progression, underlying mechanisms were not identified. Here, we use next-generation sequencing and conditional genetic methodologies to define the spatial and biological origins of spinal curve formation in ptk7 mutant zebrafish, a faithful IS model. We demonstrate that focal activation of proinflammatory signals within the spinal cord is associated with, and sufficient for, induction of spinal curvatures. Furthermore, administration of acetylsalicylic acid (aspirin) or N-acetylcysteine (NAC) to juvenile ptk7 mutants significantly reduces the incidence and/or severity of scoliosis phenotypes. Together, our results implicate neuroinflammation, downstream of CSF defects, in spinal curve formation and provide intriguing evidence that simple immunomodulating therapies might prove effective in managing idiopathic-like spinal deformities.

    As is so often the case among common diseases inflammation may be the root cause of scoliosis. That appears to be the case in the Zebrafish model that researchers use to study IS.

    Long story short: Eat your vegetables and don't eat processed food garbage. Hopefully ever. Modern, sugary food is highly inflammatory. Google for confirmation on diet and inflammation.
    Last edited by Dingo; 12-15-2018 at 11:04 AM.

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    Full study here: Neuroinflammatory signals drive spinal curve formation in zebrafish models of idiopathic scoliosis

    Although a definitive link between neuroinflammation and human IS requires further study, inflammatory origins of scoliosis are not inconsistent with human clinical and genetic studies. Hyper-IgE (immunoglobulin E) syndrome, characterized by frequent bacterial infection and inflammation, has been associated with developmental scoliosis (31). Similarly, more than 50% of patients characterized by recurring nontuberculosis mycobacterial infection present with idiopathic-like spinal curvatures (32). To date, the biological consequences of most IS-associated variants identified in genetic and genome-wide association studies remain uncertain (1). For example, IS-associated variants linked to GPR126 have been functionally interrogated largely in the context of musculoskeletal origins of scoliosis (4, 33). However, because myelination requires GPR126 (34), regional demyelinating events downstream of GPR126 dysfunction could activate microglial inflammatory signals that initiate IS-like spinal curvature. Novel neuroinflammatory origins of IS identified in this study thus warrant a reexamination and interpretation of human IS clinical and genetic data.

    Strikingly, we have demonstrated that treatment with common NSAIDs can have a significant and positive impact on the incidence and severity of scoliosis in our ptk7 mutant models. Notably, prophylactic treatment with NAC reduced the incidence of scoliosis in experimental cohorts by 79%. Furthermore, administration of NAC after scoliosis onset significantly reduced the severity of spinal curve progression. NAC is considered a well-tolerated and safe medication, with emerging clinical use for treating neurological and neurodevelopmental disorders in both children and adults [reviewed in (23, 35)]. The therapeutic potential of NAC in treating IS remains to be determined. However, given that simple immunomodulating therapies prove effective in managing zebrafish idiopathic-like spinal deformities, conservation of the mechanism could have profound impacts on the future prevention and treatment of human scoliosis.
    Last edited by Dingo; 12-15-2018 at 09:32 PM.

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    Sure enough the researchers were correct.

    Hyper-IgE syndrome update
    AD-HIES is characterized by eczematoid rashes, skin abscesses, recurrent sinopulmonary infections, mucocutaneous candidiasis, and malignancies.
    Clinical features of hyper-IgE syndrome
    Nonimmunologic frequency
    Scoliosis 63%
    Pulmonary Nontuberculous Mycobacterial Disease
    Conclusions: Patients with PNTM infection are taller and leaner than control subjects, with high rates of scoliosis, pectus excavatum, mitral valve prolapse, and cystic fibrosis transmembrane conductance regulator mutations, but without recognized immune defects.
    Last edited by Dingo; 12-15-2018 at 09:58 PM.

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    I did a few minutes of digging and once again spinal deformity is associated with infections besides Polio.

    Vertebral Osteomyelitis: Rare Spinal Infection Can Cause Severe Back Pain
    Surgery may be considered if: You develop spinal deformity (such as scoliosis or kyphosis), or the deformity worsens.
    The Zebrafish study was on the mark. Inflammation in the spine does cause deformity. It's well known.
    Last edited by Dingo; 12-17-2018 at 03:59 PM.

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    Strikingly, we have demonstrated that treatment with common NSAIDs can have a significant and positive impact on the incidence and severity of scoliosis in our ptk7 mutant models. Notably, prophylactic treatment with NAC reduced the incidence of scoliosis in experimental cohorts by 79%. Furthermore, administration of NAC after scoliosis onset significantly reduced the severity of spinal curve progression. NAC is considered a well-tolerated and safe medication, with emerging clinical use for treating neurological and neurodevelopmental disorders in both children and adults [reviewed in (23, 35)]. The therapeutic potential of NAC in treating IS remains to be determined. However, given that simple immunomodulating therapies prove effective in managing zebrafish idiopathic-like spinal deformities, conservation of the mechanism could have profound impacts on the future prevention and treatment of human scoliosis.
    Anyone tried NAC?

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