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Neurochem.<\/jats:italic> (2012) <jats:bold>121<\/jats:bold>, 302\u2013313.<\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Mounting evidence suggests a potential link between cocaine abuse, disruptions in hypothalamic\u2010pituitary\u2010thyroid axis signaling, and neuroplasticity, but molecular mechanisms remain unknown. Neurogranin (Ng) is a gene containing a thyroid hormone\u2010responsive element within its first intron that is involved in synaptic plasticity. Transcriptional activation requires heterodimerization of thyroid hormone receptor (TR) and retinoid X receptor (RXR) bound by their respective ligands, tri\u2010iodothryonine and 9\u2010<jats:italic>cis<\/jats:italic>\u2010retinoic acid (9\u2010<jats:italic>cis<\/jats:italic>\u2010RA), and subsequent binding of this complex to the thyroid hormone\u2010responsive element of the Ng gene. In this study, the effects of chronic cocaine abuse on Ng expression in euthyroid and hypothyroid mice were assessed. In cocaine\u2010treated mice, decreased Ng expression was observed in the absence of changes in levels of thyroid hormones or other hypothalamic\u2010pituitary\u2010thyroid signaling factors. Therefore, we hypothesized that cocaine decreases Ng expression via alterations in 9\u2010<jats:italic>cis<\/jats:italic>\u2010RA availability and TR\/RXR signaling. In support of this hypothesis, RXR\u2010\u03b3 was significantly decreased in brains of cocaine\u2010treated mice while CYP26A1, the main enzyme responsible for neuronal RA degradation, was significantly increased. Results from this study provide the first evidence for a direct effect of cocaine abuse on TR\/RXR signaling, RA metabolism, and transcriptional regulation of Ng, a gene essential for adult neuroplasticity.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1471-4159.2012.07678.x","type":"journal-article","created":{"date-parts":[[2012,2,2]],"date-time":"2012-02-02T16:18:20Z","timestamp":1328199500000},"page":"302-313","source":"Crossref","is-referenced-by-count":11,"title":["Cocaine decreases expression of neurogranin via alterations in thyroid receptor\/retinoid X receptor signaling"],"prefix":"10.1111","volume":"121","author":[{"given":"Jane","family":"Kovalevich","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gladys","family":"Corley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Yen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott M.","family":"Rawls","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dianne","family":"Langford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,3,13]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2003.02247.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-2567"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.3109\/00207459109150348"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0278-5846(97)00089-4"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.3109\/15622970109027495"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.3109\/10826081003777550"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1176\/jnp.10.3.280"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0029-1211463"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(96)12836-6"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80654-6"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.145.8.971"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02815101"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00422974"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0169-328X(94)00246-B"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2005.03.010"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.2105\/AJPH.77.2.178"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.3109\/00952999109001601"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2005.03.099"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(00)01508-1"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03167028"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2003-0414"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2008.01.004"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2008.07.004"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.3109\/15622975.2010.491126"},{"key":"e_1_2_7_26_1","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1001\/jama.1981.03310440019016","article-title":"Hypothyroidism and depression. 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