目的:暴饮暴食障碍是一种以暴饮暴食反复发作为特征的饮食障碍,在此期间,个人在短时间内消耗过量的高度可口的食物(HPF)。这项研究调查了反复暴饮暴食事件与两个关键基因的转录调控之间的复杂关系,腺苷A2A受体(A2AAR)和多巴胺D2受体(D2R),在选定的大鼠大脑区域。
方法:在雌性大鼠中,通过食物限制和挫折应激(暴露于HPF15分钟而不接触HPF)的组合诱导HPF的暴饮暴食行为,与仅受到限制或仅受到压力或没有这两种情况的对照大鼠相比。在长期暴饮暴食之后,从不同的大脑区域提取核酸,通过实时定量PCR评估基因表达水平。使用焦磷酸测序研究了基因启动子上的甲基化模式。
结果:分析显示杏仁核和腹侧被盖区(VTA)的A2AAR上调,暴饮暴食大鼠伏隔核中的D2R下调。同时,在A2AAR的VTA和D2R的杏仁核和尾状壳核中鉴定了基因启动子的位点特异性DNA甲基化改变。
结论:A2AAR和D2R基因调控的改变突出了表观遗传机制在暴饮暴食行为病因中的意义,并强调了有针对性的治疗干预措施的潜力,以防止这种不适应的喂养行为的发展。这些发现为饮食失调领域的未来研究提供了有价值的见解。
■使用带有面部的动物模型,construct,和预测效度,食物限制和挫折压力的循环唤起暴饮暴食行为,我们强调了表观遗传机制对腺苷A2A受体(A2AAR)和多巴胺D2受体(D2R)基因调控的意义。它们可以代表以这种不适应的进食行为为特征的进食障碍的药理学管理的新的潜在目标。
OBJECTIVE: Binge-eating disorder is an eating disorder characterized by recurrent binge-eating episodes, during which individuals consume excessive amounts of highly palatable food (HPF) in a short time. This study investigates the intricate relationship between repeated binge-eating episode and the transcriptional regulation of two key genes, adenosine A2A receptor (A2AAR) and dopamine D2 receptor (D2R), in selected brain regions of rats.
METHODS: Binge-like eating behavior on HPF was induced through the combination of food restrictions and frustration stress (15 min exposure to HPF without access to it) in female rats, compared to control rats subjected to only restriction or only stress or none of these two conditions. After chronic binge-eating episodes, nucleic acids were extracted from different brain regions, and gene expression levels were assessed through real-time quantitative PCR. The methylation pattern on genes\' promoters was investigated using pyrosequencing.
RESULTS: The analysis revealed A2AAR upregulation in the amygdala and in the ventral tegmental area (VTA), and D2R downregulation in the nucleus accumbens in binge-eating rats. Concurrently, site-specific DNA methylation alterations at gene promoters were identified in the VTA for A2AAR and in the amygdala and caudate putamen for D2R.
CONCLUSIONS: The alterations on A2AAR and D2R genes regulation highlight the significance of epigenetic mechanisms in the etiology of binge-eating behavior, and underscore the potential for targeted therapeutic interventions, to prevent the development of this maladaptive feeding behavior. These findings provide valuable insights for future research in the field of eating disorders.
UNASSIGNED: Using an animal model with face, construct, and predictive validity, in which cycles of food restriction and frustration stress evoke binge-eating behavior, we highlight the significance of epigenetic mechanisms on adenosine A2A receptor (A2AAR) and dopamine D2 receptor (D2R) genes regulation. They could represent new potential targets for the pharmacological management of eating disorders characterized by this maladaptive feeding behavior.