Standards of evidence in chronobiology: critical review of a report that restoration of Bmal1 expression in the dorsomedial hypothalamus is sufficient to restore circadian food anticipatory rhythms in Bmal1-/- mice.
Standards of evidence in chronobiology: critical review of a report that restoration of Bmal1 expression in the dorsomedial hypothalamus is sufficient to restore circadian food anticipatory rhythms in Bmal1-/- mice.
复制标题
DOI：
10.1186/1740-3391-7-3
复制
发表时间：
2009-03-26
影响因子：
--
通讯作者：
Shibata, Shigenobu
中科院分区：
文献类型：
--
作者：
Mistlberger, Ralph E;Buijs, Ruud M;Shibata, Shigenobu
每日喂养时间表产生食物预期的行为和生理节律，表现出生物钟控制的规范属性。假设控制食物预期节律的食物敏感昼夜节律振荡器的分子机制和位置尚不清楚。在2008年，Fuller等人报道，在携带生物钟基因Bmal 1无效突变的小鼠中，不存在食物耐受的昼夜节律，并且这些节律可以通过病毒介导的恢复下丘脑背内侧核（DMH）中的Bmal 1表达而不是视交叉上核（主光耐受的昼夜节律起搏器的部位）中的Bmal 1表达来拯救。这些结果，结合同一实验室发表的有争议的DMH损伤结果，似乎建立了DMH作为Bmal 1依赖性昼夜节律机制的网站，这是食物预期节律所必需和足够的。然而，对手稿的仔细检查揭示了所提出的证据中的许多弱点。这些问题分为以下几类并进行了详细阐述：1.数据管理问题（绘制数据的明显不对齐），2.没有证据支持主要结论; 3.缺少数据和方法细节。因此，Fuller等人的结果被认为是不确定的，并且未能阐明DMH或Bmal 1在啮齿动物中食物耐受性昼夜节律表达中的作用。
Daily feeding schedules generate food anticipatory rhythms of behavior and physiology that exhibit canonical properties of circadian clock control. The molecular mechanisms and location of food-entrainable circadian oscillators hypothesized to control food anticipatory rhythms are unknown. In 2008, Fuller et al reported that food-entrainable circadian rhythms are absent in mice bearing a null mutation of the circadian clock gene Bmal1 and that these rhythms can be rescued by virally-mediated restoration of Bmal1 expression in the dorsomedial nucleus of the hypothalamus (DMH) but not in the suprachiasmatic nucleus (site of the master light-entrainable circadian pacemaker). These results, taken together with controversial DMH lesion results published by the same laboratory, appear to establish the DMH as the site of a Bmal1-dependent circadian mechanism necessary and sufficient for food anticipatory rhythms. However, careful examination of the manuscript reveals numerous weaknesses in the evidence as presented. These problems are grouped as follows and elaborated in detail: 1. data management issues (apparent misalignments of plotted data), 2. failure of evidence to support the major conclusions, and 3. missing data and methodological details. The Fuller et al results are therefore considered inconclusive, and fail to clarify the role of either the DMH or Bmal1 in the expression of food-entrainable circadian rhythms in rodents.