SARM1 detection in myelinating glia: sarm1/Sarm1 is dispensable for PNS and CNS myelination in zebrafish and mice

Frontiers in Cellular Neuroscience

Neuroscience

Mark Turmaine¹  Peter Arthur-Farraj²  Michael P. Coleman²  Clara Mutschler²  Andrea Loreto²  Shaline V. Fazal³  Roger A. Barker³  Benjamin J. Steventon⁴  Chiung-Ya Chen⁵  Yi-Ping Hsueh⁵  Andrea Ibañez-Grau⁶  Hugo Cabedo⁷  Angeles Casillas-Bajo⁷  Jose A. Gomez-Sanchez⁸  Kelly R. Monk⁹  Civia Z. Chen^1,10  Robin J. M. Franklin^1,11 

[1] Department of Cell and Developmental Biology, University College London, London, United Kingdom;Department of Clinical Neurosciences, John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, United Kingdom;Department of Clinical Neurosciences, John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, United Kingdom;Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom;Department of Genetics, University of Cambridge, Cambridge, United Kingdom;Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan;Instituto de Neurociencias de Alicante, Universidad Miguel Hernández, Alicante, Spain;Instituto de Neurociencias de Alicante, Universidad Miguel Hernández, Alicante, Spain;Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), Alicante, Spain;Instituto de Neurociencias de Alicante, Universidad Miguel Hernández, Alicante, Spain;Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), Alicante, Spain;Millennium Nucleus for the Study of Pain (MiNuSPain), Santiago, Chile;Vollum Institute, Oregon Health & Science University, Portland, OR, United States;Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom;Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom;Altos Labs - Cambridge Institute of Science, Cambridge, United Kingdom;

关键词: Schwann cell;    oligodendrocyte;    myelination;    SARM1;    zebrafish;    mouse;   

DOI  :  10.3389/fncel.2023.1158388

 received in 2023-02-03, accepted in 2023-03-14,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

Unknown   
Copyright © 2023 Fazal, Mutschler, Chen, Turmaine, Chen, Hsueh, Ibañez-Grau, Loreto, Casillas-Bajo, Cabedo, Franklin, Barker, Monk, Steventon, Coleman, Gomez-Sanchez and Arthur-Farraj.