Academic Journal
SARM1 detection in myelinating glia: sarm1/Sarm1 is dispensable for PNS and CNS myelination in zebrafish and mice
| العنوان: | SARM1 detection in myelinating glia: sarm1/Sarm1 is dispensable for PNS and CNS myelination in zebrafish and mice |
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| المؤلفون: | Fazal, Shaline V., Mutschler, Clara, Chen, Civia Z., Turmaine, Mark, Chen, Chiung-Ya, Hsueh, Yi-Ping, Ibañez-Grau, Andrea, Loreto, Andrea, Casillas-Bajo, Angeles, Cabedo, Hugo, Franklin, Robin J. M., Barker, Roger A., Monk, Kelly R., Steventon, Benjamin J., Coleman, Michael P., Gómez-Sánchez, José A., Arthur-Farraj, Peter |
| المساهمون: | Medical Research Council (UK), Wellcome Trust, Royal Society (UK), National Institute of Neurological Disorders and Stroke (US), Instituto de Salud Carlos III, Generalitat Valenciana, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Ministerio de Economía y Competitividad (España), Academia Sinica (Taiwan) |
| بيانات النشر: | Frontiers Media |
| سنة النشر: | 2023 |
| المجموعة: | Digital.CSIC (Consejo Superior de Investigaciones Científicas / Spanish National Research Council) |
| الوصف: | Since SARM1 mutations have been identified in human neurological disease, SARM1 inhibition has become an attractive therapeutic strategy to preserve axons in a variety of disorders of the peripheral (PNS) and central nervous system (CNS). While SARM1 has been extensively studied in neurons, it remains unknown whether SARM1 is present and functional in myelinating glia? This is an important question to address. Firstly, to identify whether SARM1 dysfunction in other cell types in the nervous system may contribute to neuropathology in SARM1 dependent diseases? Secondly, to ascertain whether therapies altering SARM1 function may have unintended deleterious impacts on PNS or CNS myelination? Surprisingly, we find that oligodendrocytes express sarm1 mRNA in the zebrafish spinal cord and that SARM1 protein is readily detectable in rodent oligodendrocytes in vitro and in vivo. Furthermore, activation of endogenous SARM1 in cultured oligodendrocytes induces rapid cell death. In contrast, in peripheral glia, SARM1 protein is not detectable in Schwann cells and satellite glia in vivo and sarm1/Sarm1 mRNA is detected at very low levels in Schwann cells, in vivo, in zebrafish and mouse. Application of specific SARM1 activators to cultured mouse Schwann cells does not induce cell death and nicotinamide adenine dinucleotide (NAD) levels remain unaltered suggesting Schwann cells likely contain no functionally relevant levels of SARM1. Finally, we address the question of whether SARM1 is required for myelination or myelin maintenance. In the zebrafish and mouse PNS and CNS, we show that SARM1 is not required for initiation of myelination and myelin sheath maintenance is unaffected in the adult mouse nervous system. Thus, strategies to inhibit SARM1 function to treat neurological disease are unlikely to perturb myelination in humans. ; CM was funded by a Medical Research Council (UK) studentship (2251399). PA-F (206634/Z/17/Z), AL (210904/Z/18/Z), CC (220027/Z/19/Z), RB (203151/Z/16/Z) and MC (220906/Z/20/Z) were funded by the ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1662-5102 37091921 |
| Relation: | #PLACEHOLDER_PARENT_METADATA_VALUE#; info:eu-repo/grantAgreement/MINECO//BFU2016-75864-R; info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-109762RB-I00/ES/TRANSICIONES FENOTIPICAS DE LAS CELULAS DE SCHWANN DURANTE EL DESARROLLO DE LA MIELINA, LA REGENERACION NERVIOSA Y LAS NEUROPATIAS PERIFERICAS DESMILEINIZANTES HEREDITARIAS/; Publisher's version; https://doi.org/10.3389/fncel.2023.1158388; Sí; Frontiers in Cellular Neuroscience 17: 1158388 (2023); http://hdl.handle.net/10261/335177; http://dx.doi.org/10.13039/100004440; http://dx.doi.org/10.13039/100000065; http://dx.doi.org/10.13039/501100000288; http://dx.doi.org/10.13039/501100001869; http://dx.doi.org/10.13039/501100011033; http://dx.doi.org/10.13039/501100003359; http://dx.doi.org/10.13039/501100004587; http://dx.doi.org/10.13039/501100000265; http://dx.doi.org/10.13039/501100003329 |
| DOI: | 10.3389/fncel.2023.1158388 |
| DOI: | 10.13039/100004440 |
| DOI: | 10.13039/100000065 |
| DOI: | 10.13039/501100000288 |
| DOI: | 10.13039/501100001869 |
| DOI: | 10.13039/501100011033 |
| DOI: | 10.13039/501100003359 |
| DOI: | 10.13039/501100004587 |
| DOI: | 10.13039/501100000265 |
| DOI: | 10.13039/501100003329 |
| الاتاحة: | http://hdl.handle.net/10261/335177 https://doi.org/10.3389/fncel.2023.1158388 https://doi.org/10.13039/100004440 https://doi.org/10.13039/100000065 https://doi.org/10.13039/501100000288 https://doi.org/10.13039/501100001869 https://doi.org/10.13039/501100011033 https://doi.org/10.13039/501100003359 https://doi.org/10.13039/501100004587 https://doi.org/10.13039/501100000265 |
| Rights: | open |
| رقم الانضمام: | edsbas.F5752DC1 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 16625102 37091921 |
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| DOI: | 10.3389/fncel.2023.1158388 |