Division of Molecular Psychiatry, Ribicoff Research Facilities, Department of Psychiatry, Yale University School of Medicine, 34 Park Street, New Haven, CT 06508, USA.
Biol Psychiatry. 2012 Feb 15;71(4):358-65. doi: 10.1016/j.biopsych.2011.06.028.
Food restriction is known to enhance learning and motivation. The neural mechanisms underlying these responses likely involve alterations in gene expression in brain regions mediating the motivation to feed.
Analysis of gene expression profiles in male C57BL/6J mice using whole-genome microarrays was completed in the medial prefrontal cortex, nucleus accumbens, ventral tegmental area, and the hypothalamus following a 5-day food restriction. Quantitative polymerase chain reaction was used to validate these findings and determine the time course of expression changes. Plasma levels of the stress hormone corticosterone (CORT) were measured by enzyme-linked immunosorbent assay. Expression changes were measured in adrenalectomized animals that underwent food restriction, as well as in animals receiving daily injections of CORT. Progressive ratio responding for food, a measure of motivated behavior, was assessed after CORT treatment in restricted and fed animals.
Brief food restriction results in an upregulation of peripheral stress responsive genes in the mammalian brain. Time-course analysis demonstrated rapid and persistent expression changes in all four brain regions under study. Administration of CORT to nonrestricted animals was sufficient to induce a subset of the genes, and alterations in gene expression after food restriction were dependent on intact adrenal glands. CORT can increase the motivation to work for food only in the restricted state.
These data demonstrate a central role for CORT in mediating both molecular and behavioral responses to food restriction. The stress hormone-induced alterations in gene expression described here may be relevant for both adaptive and pathological responses to stress.
众所周知，限制食物摄入可以增强学习和动力。这些反应的神经机制可能涉及调节进食动机的大脑区域中基因表达的改变。
使用全基因组微阵列分析了雄性 C57BL/6J 小鼠在经历 5 天食物限制后的内侧前额叶皮层、伏隔核、腹侧被盖区和下丘脑的基因表达谱。定量聚合酶链反应用于验证这些发现并确定表达变化的时间过程。通过酶联免疫吸附试验测量应激激素皮质酮 (CORT) 的血浆水平。在接受食物限制的肾上腺切除术动物以及接受每日 CORT 注射的动物中测量了表达变化。在限制和喂食动物中给予 CORT 治疗后，评估了食物的递增比率反应，这是一种衡量动机行为的方法。
短暂的食物限制会导致哺乳动物大脑中外周应激反应基因的上调。时程分析表明，所有四个研究的大脑区域都迅速且持续地发生表达变化。非限制动物给予 CORT 足以诱导部分基因，并且食物限制后的基因表达改变依赖于完整的肾上腺。CORT 只能在限制状态下增加获取食物的动力。
这些数据表明 CORT 在介导食物限制的分子和行为反应中起核心作用。应激激素诱导的基因表达改变可能与应激的适应性和病理性反应都有关。
