{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,6,9]],"date-time":"2024-06-09T18:49:24Z","timestamp":1717958964440},"reference-count":36,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,1,29]],"date-time":"2015-01-29T00:00:00Z","timestamp":1422489600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2015,2]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Frontotemporal lobar degeneration (<jats:styled-content style=\"fixed-case\">FTLD<\/jats:styled-content>) is clinically and pathologically heterogeneous. Although associated with variations in <jats:styled-content style=\"fixed-case\"><jats:italic>MAPT<\/jats:italic><\/jats:styled-content>, <jats:styled-content style=\"fixed-case\"><jats:italic>GRN<\/jats:italic><\/jats:styled-content> and <jats:styled-content style=\"fixed-case\"><jats:italic>C9ORF72<\/jats:italic><\/jats:styled-content>, the pathogenesis of these, and of other nongenetic, forms of <jats:styled-content style=\"fixed-case\">FTLD<\/jats:styled-content>, remains unknown. Epigenetic factors such as histone regulation by histone deacetylases (<jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content>) may play a role in the dysregulation of transcriptional activity, thought to underpin the neurodegenerative process.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The distribution and intensity of <jats:styled-content style=\"fixed-case\">HDACs<\/jats:styled-content> 4, 5 and 6 was assessed semi\u2010quantitatively in immunostained sections of temporal cortex with hippocampus, and cerebellum, from 33 pathologically confirmed cases of <jats:styled-content style=\"fixed-case\">FTLD<\/jats:styled-content> and 27 controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found a significantly greater intensity of cytoplasmic immunostaining for <jats:styled-content style=\"fixed-case\">HDAC4<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">HDAC6<\/jats:styled-content> in granule cells of the dentate gyrus in cases of <jats:styled-content style=\"fixed-case\">FTLD<\/jats:styled-content> overall compared with controls, and specifically in cases of <jats:styled-content style=\"fixed-case\">FTLD<\/jats:styled-content> tau\u2010<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>icks compared with <jats:styled-content style=\"fixed-case\">FTLD<\/jats:styled-content> tau\u2010<jats:styled-content style=\"fixed-case\"><jats:italic>MAPT<\/jats:italic><\/jats:styled-content> and controls. No differences were noted between <jats:styled-content style=\"fixed-case\">FTLD<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">TDP<\/jats:styled-content> subtypes, or between the different genetic and nongenetic forms of <jats:styled-content style=\"fixed-case\">FTLD<\/jats:styled-content>. No changes were seen in <jats:styled-content style=\"fixed-case\">HDAC5<\/jats:styled-content> in any <jats:styled-content style=\"fixed-case\">FTLD<\/jats:styled-content> or control cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Dysregulation of <jats:styled-content style=\"fixed-case\">HDAC4<\/jats:styled-content> and\/or <jats:styled-content style=\"fixed-case\">HDAC6<\/jats:styled-content> could play a role in the pathogenesis of <jats:styled-content style=\"fixed-case\">FTLD<\/jats:styled-content>\u2010tau associated with Pick bodies, although their lack of immunostaining implies that such changes do not contribute directly to the formation of <jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>ick bodies.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nan.12153","type":"journal-article","created":{"date-parts":[[2014,5,27]],"date-time":"2014-05-27T11:08:11Z","timestamp":1401188891000},"page":"245-257","source":"Crossref","is-referenced-by-count":9,"title":["Histone deacetylases (<scp>HDACs<\/scp>) in frontotemporal lobar degeneration"],"prefix":"10.1111","volume":"41","author":[{"given":"Amy","family":"Whitehouse","sequence":"first","affiliation":[{"name":"Clinical and Cognitive Sciences Research Group Institute of Brain, Behaviour and Mental Health Faculty of Medical and Human Sciences University of Manchester, Salford Royal Hospital  Salford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klara","family":"Doherty","sequence":"additional","affiliation":[{"name":"Clinical and Cognitive Sciences Research Group Institute of Brain, Behaviour and Mental Health Faculty of Medical and Human Sciences University of Manchester, Salford Royal Hospital  Salford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsin Hsien","family":"Yeh","sequence":"additional","affiliation":[{"name":"Clinical and Cognitive Sciences Research Group Institute of Brain, Behaviour and Mental Health Faculty of Medical and Human Sciences University of Manchester, Salford Royal Hospital  Salford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew C.","family":"Robinson","sequence":"additional","affiliation":[{"name":"Clinical and Cognitive Sciences Research Group Institute of Brain, Behaviour and Mental Health Faculty of Medical and Human Sciences University of Manchester, Salford Royal Hospital  Salford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Rollinson","sequence":"additional","affiliation":[{"name":"Clinical and Cognitive Sciences Research Group Institute of Brain, Behaviour and Mental Health Faculty of Medical and Human Sciences University of Manchester  A.V Hill Building Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stuart","family":"Pickering\u2010Brown","sequence":"additional","affiliation":[{"name":"Clinical and Cognitive Sciences Research Group Institute of Brain, Behaviour and Mental Health Faculty of Medical and Human Sciences University of Manchester  A.V Hill Building Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie","family":"Snowden","sequence":"additional","affiliation":[{"name":"Clinical and Cognitive Sciences Research Group Institute of Brain, Behaviour and Mental Health Faculty of Medical and Human Sciences University of Manchester, Salford Royal Hospital  Salford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer C","family":"Thompson","sequence":"additional","affiliation":[{"name":"Clinical and Cognitive Sciences Research Group Institute of Brain, Behaviour and Mental Health Faculty of Medical and Human Sciences University of Manchester, Salford Royal Hospital  Salford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yvonne S.","family":"Davidson","sequence":"additional","affiliation":[{"name":"Clinical and Cognitive Sciences Research Group Institute of Brain, Behaviour and Mental Health Faculty of Medical and Human Sciences University of Manchester, Salford Royal Hospital  Salford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David M. 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