{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:19:28Z","timestamp":1784557168410,"version":"3.55.0"},"reference-count":46,"publisher":"Bioscientifica","issue":"2","content-domain":{"domain":["joe.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:p>\n                    Thyroid hormone (TH) through its receptor (TR\u03b1\/\u03b2) influences spatio-temporal regulation of its target gene repertoire during brain development. Though hypothyroidism in WT rodent models of perinatal hypothyroidism severely impairs neurodevelopment, its effect on TR\u03b1\/\u03b2 knockout mice is less severe. An explanation to this paradox is attributed to a possible repressive action of unliganded TRs during development. Since unliganded TRs suppress gene expression through the recruitment of histone deacetylase (HDACs) via co-repressor complexes, we tested whether pharmacological inhibition of HDACs may prevent the effects of hypothyroidism on brain development. Using valproate, an HDAC inhibitor, we show that HDAC inhibition significantly blocks the deleterious effects of hypothyroidism on rat cerebellum, evident by recovery of TH target genes like\n                    <jats:italic>Bdnf<\/jats:italic>\n                    ,\n                    <jats:italic>Pcp2<\/jats:italic>\n                    and\n                    <jats:italic>Mbp<\/jats:italic>\n                    as well as improved dendritic structure of cerebellar Purkinje neurons. Together with this, HDAC inhibition also rescues hypothyroidism-induced motor and cognitive defects. This study therefore provides an insight into the role of HDACs in TH insufficiency during neurodevelopment and their inhibition as a possible therapeutics for treatment.\n                  <\/jats:p>","DOI":"10.1530\/joe-15-0168","type":"journal-article","created":{"date-parts":[[2015,10,1]],"date-time":"2015-10-01T22:54:03Z","timestamp":1443740043000},"page":"83-92","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":12,"title":["Histone deacetylase inhibition reduces hypothyroidism-induced neurodevelopmental defects in rats"],"prefix":"10.1530","volume":"227","author":[{"given":"Praveen","family":"Kumar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishwa","family":"Mohan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohit Anthony","family":"Sinha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megha","family":"Chagtoo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madan M","family":"Godbole","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"2015110216231867000_227.2.83.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0303-7207(97)00095-6"},{"key":"2015110216231867000_227.2.83.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2012.07.001"},{"key":"2015110216231867000_227.2.83.3","doi-asserted-by":"crossref","unstructured":"Bernal J Morte B 2013 Thyroid hormone receptor activity in the absence of ligand: physiological and developmental implications. 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