{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T19:07:28Z","timestamp":1777662448451,"version":"3.51.4"},"reference-count":50,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2015,10,9]],"date-time":"2015-10-09T00:00:00Z","timestamp":1444348800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008568","name":"Center for Advanced Systems and Engineering, Syracuse University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008568","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005468","name":"Batten Disease Support and Research Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005468","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001543","name":"Neurological Foundation of New Zealand","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001543","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005725","name":"CHDI Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>Synapses represent a major pathological target across a broad range of neurodegenerative conditions. Recent studies addressing molecular mechanisms regulating synaptic vulnerability and degeneration have relied heavily on invertebrate and mouse models. Whether similar molecular neuropathological changes underpin synaptic breakdown in large animal models and in human patients with neurodegenerative disease remains unclear. We therefore investigated whether molecular regulators of synaptic pathophysiology, previously identified in Drosophila and mouse models, are similarly present and modified in the brain of sheep with <jats:styled-content style=\"fixed-case\">CLN<\/jats:styled-content>5 Batten disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Gross neuropathological analysis of <jats:styled-content style=\"fixed-case\">CLN<\/jats:styled-content>5 Batten disease sheep and controls was used alongside postmortem <jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content> imaging to identify affected brain regions. Synaptosome preparations were then generated and quantitative fluorescent Western blotting used to determine and compare levels of synaptic proteins.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The cortex was particularly affected by regional neurodegeneration and synaptic loss in <jats:styled-content style=\"fixed-case\">CLN<\/jats:styled-content>5 sheep, whilst the cerebellum was relatively spared. Quantitative assessment of the protein content of synaptosome preparations revealed significant changes in levels of seven out of eight synaptic neurodegeneration proteins investigated in the motor cortex, but not cerebellum, of <jats:styled-content style=\"fixed-case\">CLN<\/jats:styled-content>5 sheep (<jats:italic>\u03b1<\/jats:italic>\u2010synuclein, <jats:styled-content style=\"fixed-case\">CSP<\/jats:styled-content>\u2010<jats:italic>\u03b1<\/jats:italic>, neurofascin, <jats:styled-content style=\"fixed-case\">ROCK<\/jats:styled-content>2, calretinin, <jats:styled-content style=\"fixed-case\">SIRT<\/jats:styled-content>2, and <jats:styled-content style=\"fixed-case\">UBR<\/jats:styled-content>4).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Synaptic pathology is a robust correlate of region\u2010specific neurodegeneration in the brain of <jats:styled-content style=\"fixed-case\">CLN<\/jats:styled-content>5 sheep, driven by molecular pathways similar to those reported in Drosophila and rodent models. Thus, large animal models, such as sheep, represent ideal translational systems to develop and test therapeutics aimed at delaying or halting synaptic pathology for a range of human neurodegenerative conditions.<\/jats:p><\/jats:sec>","DOI":"10.1002\/brb3.401","type":"journal-article","created":{"date-parts":[[2015,10,9]],"date-time":"2015-10-09T05:46:41Z","timestamp":1444369601000},"source":"Crossref","is-referenced-by-count":25,"title":["Molecular neuropathology of the synapse in sheep with <scp>CLN<\/scp>5 Batten disease"],"prefix":"10.1002","volume":"5","author":[{"given":"In\u00eas S.","family":"Amorim","sequence":"first","affiliation":[{"name":"Centre for Integrative Physiology University of Edinburgh Hugh Robson Building Edinburgh UK"},{"name":"Euan MacDonald Centre for Motor Neurone Disease Research University of Edinburgh Hugh Robson Building Edinburgh UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadia L.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences Faculty of Agricultural and Life Sciences and Batten Animal Research Network Lincoln University Christchurch New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David N.","family":"Palmer","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences Faculty of Agricultural and Life Sciences and Batten Animal Research Network Lincoln University Christchurch New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen J.","family":"Sawiak","sequence":"additional","affiliation":[{"name":"Department of Physiology, Development and Neuroscience University of Cambridge Downing Street Cambridge UK"},{"name":"Wolfson Brain Imaging Centre University of Cambridge Box\u00a065 Addenbrooke's Hospital Hills Road Cambridge 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