Show simple item record

Files in this item


Item metadata

dc.contributor.authorBroadhead, Matthew J.
dc.contributor.authorBonthron, Calum
dc.contributor.authorWaddington, Julia
dc.contributor.authorSmith, William V.
dc.contributor.authorLopez, Maite F.
dc.contributor.authorBurley, Sarah
dc.contributor.authorValli, Jessica
dc.contributor.authorZhu, Fei
dc.contributor.authorKomiyama, Noboru H.
dc.contributor.authorSmith, Colin
dc.contributor.authorGrant, Seth G.N.
dc.contributor.authorMiles, Gareth B.
dc.identifier.citationBroadhead , 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 .
dc.identifier.otherORCID: /0000-0002-8624-4625/work/110423178
dc.descriptionAuthors 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.abstractAmyotrophic 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.relation.ispartofActa Neuropathologicaen
dc.subjectRC0321 Neuroscience. Biological psychiatry. Neuropsychiatryen
dc.subjectSDG 3 - Good Health and Well-beingen
dc.titleSelective vulnerability of tripartite synapses in Amyotrophic Lateral Sclerosisen
dc.typeJournal articleen
dc.contributor.sponsorChief Scientist Officeen
dc.contributor.sponsorMotor Neurone Disease Associationen
dc.contributor.institutionUniversity of St Andrews. School of Psychology and Neuroscienceen
dc.contributor.institutionUniversity of St Andrews. School of Biologyen
dc.contributor.institutionUniversity of St Andrews. Sir James Mackenzie Institute for Early Diagnosisen
dc.contributor.institutionUniversity of St Andrews. Centre for Biophotonicsen
dc.contributor.institutionUniversity of St Andrews. Institute of Behavioural and Neural Sciencesen
dc.description.statusPeer revieweden

This item appears in the following Collection(s)

Show simple item record