The epigenetic effect of nicotine on dopamine D1 receptor expression in rat prefrontal cortex
The epigenetic effect of nicotine on dopamine D1 receptor expression in rat prefrontal cortex
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DOI：
10.1002/syn.21659
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发表时间：
2013-09-01
期刊：
影响因子：
2.3
通讯作者：
Pogun, Sakire
中科院分区：
文献类型：
--
作者：
Gozen, Oguz;Balkan, Burcu;Pogun, Sakire
尼古丁是一种高度上瘾的药物，其作用部分是通过引起多巴胺释放，从而增加大脑奖励系统中突触内的多巴胺水平。多巴胺D_1受体(DRD_1受体)及其受体定位于接受胆碱能输入的奖赏相关脑区。这项研究的目的是评估尼古丁给药是否影响DRD1s的表达，如果是，是否涉及表观遗传机制，如组蛋白乙酰化。20只雄性SD大鼠给予尼古丁(0.4 mg/kg/d，S.C.)。或注射生理盐水15天。尼古丁/生理盐水处理后，灌流生理盐水，解剖大鼠的前额叶(PFC)、纹状体(STR)和腹侧被盖区(VTA)。将匀浆分成两部分进行总RNA提取和组蛋白H4乙酰化研究。尼古丁治疗组的PFC中DRD1mRNA的表达显著高于对照组；在VTA和STR中也观察到了类似的趋势。为了研究表观遗传调控，我们在PFC样本中研究了DRD1基因启动子上游2kb区域的组蛋白H4乙酰化。用抗乙酰化组蛋白H4抗体对染色质进行免疫沉淀后，我们发现两对不同的引物均能促进组蛋白乙酰化，使-1365扩增至-1202(P
Nicotine is a highly addictive drug and exerts its effect partially through causing dopamine release, thereby increasing intrasynaptic dopamine levels in the brain reward systems. Dopaine D1 receptor (DRD1) mRNAs and receptors are localized in reward-related brain regions, which receive cholinergic input. The aim of this study is to evaluate whether nicotine administration affects the expression of DRD1s, and if so, whether epigenetic mechanisms, such as histone acetylation, are involved. Twenty Male Sprague Dawley rats received nicotine (0.4 mg/kg/day, s.c.) or saline injections for 15 days. After nicotine/saline treatment, rats were perfused with saline; prefrontal cortex (PFC), corpus striatum (STR), and ventral tegmental area (VTA) were dissected. Homogenates were divided into two parts for total RNA isolation and histone H4 acetylation studies. DRD1 mRNA expression was significantly higher in the PFC of the nicotine-treated group compared with controls; similar trends were observed in the VTA and STR. To study epigenetic regulation, the 2kb upstream region of the DRD1 gene promoter was investigated for histone H4 acetylation in PFC samples. After chromatin immunoprecipitation with anti-acetyl histone H4 antibody, we found an increase in histone acetylation by two different primer pairs which amplified the -1365 to -1202 (P