{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T11:46:44Z","timestamp":1790509604481,"version":"4.1.0"},"reference-count":81,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,2,17]],"date-time":"2021-02-17T00:00:00Z","timestamp":1613520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Neurosci."],"abstract":"<jats:p>\n                    Huntington\u2019s disease (HD) is an autosomal dominant neurodegenerative disease characterized by a late clinical onset of psychiatric, cognitive, and motor symptoms. Transcriptional dysregulation is an early and central disease mechanism which is accompanied by epigenetic alterations in HD. Previous studies demonstrated that targeting transcriptional changes by inhibition of histone deacetylases (HDACs), especially the class I HDACs, provides therapeutic effects. Yet, their exact mechanisms of action and the features of HD pathology, on which these inhibitors act remain to be elucidated. Here, using transcriptional profiling, we found that selective inhibition of HDAC1 and HDAC3 by RGFP109 alleviated transcriptional dysregulation of a number of genes, including the transcription factor genes\n                    <jats:italic>Neurod2<\/jats:italic>\n                    and\n                    <jats:italic>Nr4a2<\/jats:italic>\n                    , and gene sets and programs, especially those that are associated to insulin-like growth factor pathway, in the striatum of R6\/1 mice. RGFP109 treatment led to a modest improvement of the motor skill learning and coordination deficit on the RotaRod test, while it did not alter the locomotor and anxiety-like phenotypes in R6\/1 animals. We also found, by volumetric MRI, a widespread brain atrophy in the R6\/1 mice at the symptomatic disease stage, on which RGFP109 showed no significant effects. Collectively, our combined work suggests that specific HDAC1 and HDAC3 inhibition may offer benefits for alleviating the motor phenotypic deficits and transcriptional dysregulation in HD.\n                  <\/jats:p>","DOI":"10.3389\/fnmol.2021.616886","type":"journal-article","created":{"date-parts":[[2021,2,20]],"date-time":"2021-02-20T04:26:32Z","timestamp":1613795192000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":29,"title":["The Effects of Selective Inhibition of Histone Deacetylase 1 and 3 in Huntington\u2019s Disease Mice"],"prefix":"10.3389","volume":"14","author":[{"given":"Katharina","family":"Hecklau","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Mueller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan Paul","family":"Koch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa Hussain","family":"Mehkary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Busra","family":"Kilic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Harms","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Boehm-Sturm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferah","family":"Yildirim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,2,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2207","DOI":"10.1093\/brain\/120.12.2207","article-title":"Cognitive deficits in Huntington\u2019s disease are predicted by dopaminergic PET markers and brain volumes.","volume":"120","author":"Backman","year":"1997","journal-title":"Brain"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0216596","article-title":"Magnetic resonance imaging of mouse brain networks plasticity following motor learning.","volume":"14","author":"Badea","year":"2019","journal-title":"PLoS One"},{"key":"B3","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.brainresbull.2011.07.009","article-title":"Light and electron microscopic characterization of the evolution of cellular pathology in the R6\/1 Huntington\u2019s disease transgenic mice.","volume":"88","author":"Bayram-Weston","year":"2012","journal-title":"Brain Res. 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