Hyperactive hypothalamus, motivated and non-distractible chronic overeating in ADAR2 transgenic mice.
Hyperactive hypothalamus, motivated and non-distractible chronic overeating in ADAR2 transgenic mice.
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DOI：
10.1111/gbb.12020
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发表时间：
2013-04
期刊：
影响因子：
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通讯作者：
Singh M
中科院分区：
文献类型：
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作者：
Akubuiro A;Bridget Zimmerman M;Boles Ponto LL;Walsh SA;Sunderland J;McCormick L;Singh M
错误表达RNA编辑酶ADAR 2（作用于RNA的腺苷脱氨酶）的ADAR 2转基因小鼠表现出暴饮暴食的特征，并经历成年期肥胖。在这些转基因小鼠中，行为模式和大脑变化与可能的成瘾性暴饮暴食有关，因为转基因小鼠表现出慢性暴食症。ADAR 2转基因小鼠在竞争性奖励环境中的食物偏好和暴饮暴食的动机进行了评估，并随意获得跑步轮和食物。用[18 F]氟脱氧葡萄糖正电子发射断层扫描（FDG-PET）评估脑和外周组织的代谢活性，并检测下丘脑和纹状体的摄食相关基因、ADAR 2、多巴胺和阿片受体的RNA表达。结果表明，ADAR 2转基因小鼠表现出（1）对高脂肪含量饮食的食物偏好，（2）在竞争性奖励环境中不受干扰的食物摄入量显著增加，（3）ADAR 2、5-羟色胺2C受体（5 HT 2CR）、D1、D2、和μ阿片受体，CRH mRNA无变化，下丘脑中ADAR 2蛋白表达显著降低，（4）D1受体显著增加，生物胺改变，ADAR 2无变化，（5）下丘脑、脑干、右侧海马、左右中脑区和肩胛上周围组织的葡萄糖代谢显著高于对照组。这些结果表明，ADAR 2转基因小鼠的高度动机和目标导向的暴饮暴食行为与改变喂养，奖励相关的mRNA，和过度活跃的大脑中边缘区。
ADAR2 transgenic mice misexpressing the RNA editing enzyme ADAR2 (Adenosine Deaminase that act on RNA) show characteristics of overeating and experience adult onset obesity. Behavioral patterns and brain changes related to a possible addictive overeating in these transgenic mice were explored as transgenic mice display chronic hyperphagia. ADAR2 transgenic mice were assessed in their food preference and motivation to overeat in a competing reward environment with ad lib access to a running wheel and food. Metabolic activity of brain and peripheral tissue were assessed with [18F] fluorodeoxyglucose positron emission tomography (FDG-PET) and RNA expression of feeding related genes, ADAR2, dopamine and opiate receptors from the hypothalamus and striatum were examined. The results indicate that ADAR2 transgenic mice exhibit, (1) a food preference for diets with higher fat content, (2) significantly increased food intake that is non-distractible in a competing reward environment, (3) significantly increased mRNA expressions of ADAR2, serotonin 2C receptor (5HT2CR), D1, D2, and mu opioid receptors and no change in CRH mRNAs and significantly reduced ADAR2 protein expression in the hypothalamus, (4) significantly increased D1 receptor and altered bioamines with no change in ADAR2, mu opioid and D2 receptor mRNA expression in the striatum, and (5) significantly greater glucose metabolism in the hypothalamus, brain stem, right hippocampus, left and right mid brain regions and suprascapular peripheral tissue than controls. These results suggest that highly motivated and goal-oriented overeating behaviors of ADAR2 transgenic mice are associated with altered feeding, reward-related mRNAs, and hyperactive brain mesolimbic region.