Enteric Neuroscience Program (ENSP), Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Department of Endocrinology, Diabetes and Metabolism, Mayo Clinic, Rochester, Minnesota, USA.
Neurogastroenterol Motil. 2024 Apr;36(4):e14771. doi: 10.1111/nmo.14771. Epub 2024 Feb 23.
In preclinical studies whole gut transit (WGT) in mice is a gold-standard "leading-edge" approach that measures the time between orogastric gavage of carmine red and defecation of the first carmine red pellet. Transit studies in humans are performed during the active day because GI motility and transit are suppressed during the night. Since mice are nocturnal, WGT studies traditionally done during the day occur during their rest phase. How circadian rhythm affects WGT in mice is not known.
We used an automated approach for high temporal resolution uninterrupted testing of mouse WGT and activity. We housed wild-type Bl6/C57 mice under the standard 12 h light-dark cycles. At 8 weeks, we performed carmine red orogastric gavage and assessed WGT during Light (rest) conditions. Then, we exposed mice to a reverse 12 h light-dark cycle for 2 weeks and tested them in the Dark (active) under red light conditions. Timelapse videos were analyzed to quantify activity and to timestamp all pellets, and multiple parameters were analyzed.
When complementary light cycle reversal experiments were performed, we found a significant increase in mouse activity when mice were tested during their Dark (active) phase, compared to their Light (rest) phase. In mice tested in the Active phase compared to the Rest phase, we found a significant acceleration in WGT, increased rate and total number of pellets produced, and more pellet clustering. These data show that the mice tested in the Active phase have important differences in activity that correlate with multiple alterations in gastrointestinal transit.
CONCLUSION & INFERENCES: During the Active phase mice have faster WGT, produce more pellets, and cluster their output compared to testing in the Rest phase. Like in humans, circadian rhythm is an important consideration for transit studies in mice, and a simple reverse light cycle approach facilitates further studies on the role of circadian rhythm in GI motility.
在临床前研究中，小鼠的全肠道转运（WGT）是一种测量胃饲胭脂红与第一次胭脂红丸排出之间时间的“前沿”黄金标准方法。人类的转运研究在活动日进行，因为 GI 运动和转运在夜间受到抑制。由于小鼠是夜间活动的，因此传统上在白天进行的 WGT 研究发生在它们的休息期。昼夜节律如何影响小鼠的 WGT 尚不清楚。
我们使用一种自动化方法来进行高时间分辨率的不间断小鼠 WGT 和活动测试。我们将野生型 Bl6/C57 小鼠饲养在标准的 12 小时光照-黑暗循环中。在 8 周时，我们进行了胭脂红胃饲，并在光照（休息）条件下评估了 WGT。然后，我们将小鼠暴露于反向的 12 小时光照-黑暗循环中 2 周，并在黑暗（活动）条件下用红光对它们进行测试。延时视频用于分析以量化活动并标记所有丸剂，并且分析了多个参数。
当进行互补的光照周期反转实验时，我们发现当小鼠在其黑暗（活动）期进行测试时，与在光照（休息）期相比，其活动显著增加。与在休息期相比，在活动期接受测试的小鼠中，WGT 明显加快，产生的丸剂速度和总数增加，并且丸剂聚集更多。这些数据表明，在活动期接受测试的小鼠在活动方面有重要差异，这些差异与胃肠道转运的多种改变相关。
在活动期，与在休息期相比，小鼠的 WGT 更快，产生的丸剂更多，并且它们的输出更集中。与人类一样，昼夜节律是小鼠转运研究的一个重要考虑因素，而简单的反转光照周期方法有助于进一步研究昼夜节律在 GI 运动中的作用。
