ABSTRACT

Circadian disruptions, including exposure to constant light, are known to produce behavioral and physiological issues. However, sex differences exist in how those problems manifest, as males tend to have increased susceptibility to the negative consequences of circadian disruption. As gonadal hormones play a role in circadian timekeeping, we decided to investigate whether ovariectomized C57BL6/J mice would exhibit increased behavioral and physiological sensitivity to constant light compared to female mice with intact estrogen circulation. Mice, half of which underwent an ovariectomy and the other half received sham surgery, were then placed in either constant light or a 12:12 light-dark cycle. After six weeks of photoperiod exposure, we measured their circadian locomotor activity, anxiety-like behaviors and physiological responses. Mice which underwent ovariectomy and placed into constant light experienced altered glucose levels and reduced robustness of the circadian rhythm, with some becoming arrhythmic, compared to sham surgery animals in constant light. Additionally, ovariectomy led to delayed circadian activity onsets and reduced both home-cage and novelty-induced activity. Meanwhile, constant light produced increases to ambulatory activity in the behavioral assays and reduced circadian home-cage activity. These results indicate that removal of the ovaries can mediate the circadian, behavioral, and physiological responses to continuous light.

摘要

众所周知，昼夜节律紊乱，包括暴露在持续光照下，会产生行为和生理问题。然而，这些问题的表现方式存在性别差异，因为男性往往更容易受到昼夜节律紊乱的负面影响。由于性腺激素在昼夜节律中发挥作用，我们决定研究与具有完整雌激素循环的雌性小鼠相比，去卵巢的 C57BL6/J 小鼠是否会对恒定光表现出更高的行为和生理敏感性。然后将一半接受卵巢切除术和另一半接受假手术的小鼠置于恒定光照或 12:12 明暗循环中。经过六周的光周期照射，我们测量了它们的昼夜运动活动、焦虑样行为和生理反应。与在恒定光照下的假手术动物相比，接受卵巢切除术并置于恒定光照下的小鼠经历了葡萄糖水平的改变和昼夜节律的稳健性降低，其中一些变得心律不齐。此外，卵巢切除术导致延迟的昼夜节律活动开始，并减少了家庭笼子和新奇诱导的活动。同时，持续的光照增加了行为分析中的走动活动，并降低了昼夜节律的家笼活动。这些结果表明，切除卵巢可以调节对连续光的昼夜节律、行为和生理反应。卵巢切除术导致延迟的昼夜节律活动开始，并减少了家庭笼子和新奇诱导的活动。同时，持续的光照增加了行为分析中的走动活动，并降低了昼夜节律的家笼活动。这些结果表明，切除卵巢可以调节对连续光的昼夜节律、行为和生理反应。卵巢切除术导致延迟的昼夜节律活动开始，并减少了家庭笼子和新奇诱导的活动。同时，持续的光照增加了行为分析中的走动活动，并降低了昼夜节律的家笼活动。这些结果表明，切除卵巢可以调节对连续光的昼夜节律、行为和生理反应。