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Selective vulnerability of tripartite synapses in Amyotrophic Lateral Sclerosis
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dc.contributor.author | Broadhead, Matthew J. | |
dc.contributor.author | Bonthron, Calum | |
dc.contributor.author | Waddington, Julia | |
dc.contributor.author | Smith, William V. | |
dc.contributor.author | Lopez, Maite F. | |
dc.contributor.author | Burley, Sarah | |
dc.contributor.author | Valli, Jessica | |
dc.contributor.author | Zhu, Fei | |
dc.contributor.author | Komiyama, Noboru H. | |
dc.contributor.author | Smith, Colin | |
dc.contributor.author | Grant, Seth G.N. | |
dc.contributor.author | Miles, Gareth B. | |
dc.date.accessioned | 2022-03-24T09:41:02Z | |
dc.date.available | 2022-03-24T09:41:02Z | |
dc.date.issued | 2022-04 | |
dc.identifier.citation | Broadhead , M J , Bonthron , C , Waddington , J , Smith , W V , Lopez , M F , Burley , S , Valli , J , Zhu , F , Komiyama , N H , Smith , C , Grant , S G N & Miles , G B 2022 , ' Selective vulnerability of tripartite synapses in Amyotrophic Lateral Sclerosis ' , Acta Neuropathologica , vol. 143 , no. 4 , pp. 471–486 . https://doi.org/10.1007/s00401-022-02412-9 | en |
dc.identifier.issn | 0001-6322 | |
dc.identifier.other | PURE: 278212479 | |
dc.identifier.other | PURE UUID: 728ea93c-b880-4391-a4af-0c8072c72323 | |
dc.identifier.other | Scopus: 85126534248 | |
dc.identifier.other | ORCID: /0000-0002-8624-4625/work/110423178 | |
dc.identifier.other | WOS: 000770724000001 | |
dc.identifier.uri | http://hdl.handle.net/10023/25081 | |
dc.description | Authors would like to acknowledge the following funders: Motor Neurone Disease (MND) Association UK (Miles/Apr18/863-791), the Euan MacDonald Centre and Chief Scientist Office, The European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Programme (695568 SYNNOVATE), Simons Foundation Autism Research Initiative (529085), and the Wellcome Trust (Technology Development grant 202932). | en |
dc.description.abstract | Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disorder. Separate lines of evidence suggest that synapses and astrocytes play a role in the pathological mechanisms underlying ALS. Given that astrocytes make specialised contacts with some synapses, called tripartite synapses, we hypothesise that tripartite synapses could act as the fulcrum of disease in ALS. To test this hypothesis, we have performed an extensive microscopy-based investigation of synapses and tripartite synapses in the spinal cord of ALS model mice and post-mortem human tissue from ALS cases. We reveal widescale synaptic changes at the early symptomatic stages of the SOD1G93a mouse model. Super-resolution microscopy reveals that large complex postsynaptic structures are lost in ALS mice. Most surprisingly, tripartite synapses are selectively lost, while non-tripartite synapses remain in equal number to healthy controls. Finally, we also observe a similar selective loss of tripartite synapses in human post-mortem ALS spinal cords. From these data we conclude that tripartite synaptopathy is a key hallmark of ALS. | |
dc.language.iso | eng | |
dc.relation.ispartof | Acta Neuropathologica | en |
dc.rights | Copyright © The Author(s) 2022. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. | en |
dc.subject | ALS/MND | en |
dc.subject | Synapse | en |
dc.subject | Astrocyte | en |
dc.subject | Neurodegeneration | en |
dc.subject | RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry | en |
dc.subject | NDAS | en |
dc.subject | SDG 3 - Good Health and Well-being | en |
dc.subject.lcc | RC0321 | en |
dc.title | Selective vulnerability of tripartite synapses in Amyotrophic Lateral Sclerosis | en |
dc.type | Journal article | en |
dc.contributor.sponsor | Chief Scientist Office | en |
dc.contributor.sponsor | Motor Neurone Disease Association | en |
dc.description.version | Publisher PDF | en |
dc.contributor.institution | University of St Andrews. School of Psychology and Neuroscience | en |
dc.contributor.institution | University of St Andrews. School of Biology | en |
dc.contributor.institution | University of St Andrews. Sir James Mackenzie Institute for Early Diagnosis | en |
dc.contributor.institution | University of St Andrews. Centre for Biophotonics | en |
dc.contributor.institution | University of St Andrews. Institute of Behavioural and Neural Sciences | en |
dc.identifier.doi | https://doi.org/10.1007/s00401-022-02412-9 | |
dc.description.status | Peer reviewed | en |
dc.identifier.grantnumber | 3752534 | en |
dc.identifier.grantnumber | 137/813 | en |
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