Axonal spheroids are hallmark features of neurodegeneration, forming along degenerating axons and contributing to disease progression. Despite their ubiquity across degenerative etiologies, the dynamics of spheroid disappearance, as well as their interactions with glial cells, remain poorly understood. Here, using an zebrafish model of peripheral nerve injury, we identified several patterns of spheroid disappearance that are regulated by Schwann cells. These results describe spheroid dynamics across their lifetimes, establish a role for the extra-axonal environment in altering spheroid outcomes, and identify a cellular mechanism whereby spheroid fates are altered.
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http://dx.doi.org/10.1101/2024.11.08.622649 | DOI Listing |
PLoS One
December 2024
Department of Orthopaedic Surgery, Kyoto University, Kyoto, Japan.
Unlabelled: Human umbilical cord-derived mesenchymal stromal cells (UC-MSCs), which can be prepared in advance and are presumed to be advantageous for nerve regeneration, have potential as a cell source for Bio 3D conduits. The purpose of this study was to evaluate the nerve regeneration ability of Bio 3D conduits made from UC-MSCs using a rat sciatic nerve defect model.
Methods: A Bio 3D conduit was fabricated using a Bio 3D printer by placing UC-MSC spheroids into thin needles according to predesigned 3D data.
Epileptic Disord
December 2024
Department of Neurology, Seoul National University Hospital, and College of Medicine, Seoul National University, Seoul, Korea.
Neurobiol Dis
December 2024
Mater Research Institute-University of Queensland, Translational Research Institute, Woolloongabba, QLD 4102, Australia. Electronic address:
Amino acid substitutions in the kinase domain of the human CSF1R protein are associated with autosomal dominant adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). To model the human disease, we created a disease-associated mutation (Glu631Lys; E631K) in the mouse Csf1r locus. Previous analysis demonstrated that heterozygous mutation (Csf1r) had a dominant inhibitory effect on CSF1R signaling in vitro and in vivo but did not recapitulate human disease pathology.
View Article and Find Full Text PDFbioRxiv
November 2024
Department of Biology, University of Virginia, 485 McCormick Road, P.O. Box 400328, Charlottesville, VA, 22904-4328, USA.
Axonal spheroids are hallmark features of neurodegeneration, forming along degenerating axons and contributing to disease progression. Despite their ubiquity across degenerative etiologies, the dynamics of spheroid disappearance, as well as their interactions with glial cells, remain poorly understood. Here, using an zebrafish model of peripheral nerve injury, we identified several patterns of spheroid disappearance that are regulated by Schwann cells.
View Article and Find Full Text PDFNeurodegener Dis Manag
October 2024
Vigil Neuroscience, Inc., Watertown, MA 02472, USA.
To identify and raise awareness of healthcare service gaps for individuals with adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). An ALSP patient journey map from symptom onset throughout disease course was developed using existing literature, patient and clinician feedback from a structured workshop and community survey data regarding attitudes toward genetic testing. ALSP diagnosis is frequently delayed due to low awareness of this rare condition and symptom overlap with more common neurological conditions.
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