The Period Circadian Regulator 2 (Per2) gene is important for the modulation of circadian rhythms that influence biological processes. Circadian control of the hypothalamus-pituitary-adrenal (HPA) axis is critical for regulation of hormones involved in the stress response. Dysregulation of the HPA axis is associated with neuropsychiatric disorders. Therefore, it is important to understand how disruption of the circadian rhythm alters the HPA axis. One way to address this question is to delete a gene involved in regulating a central circadian gene such as Per2 in an animal model and to determine how this deletion may affect the HPA axis and behaviors that are altered when the HPA axis is dysregulated. To study this, corticosterone (CORT) levels were measured through the transition from light (inactive phase) to dark (active phase). Additionally, CORT levels as well as pituitary and adrenal mRNA expression were measured following a mild restraint stress. Mice were tested for depressive-like behaviors (forced swim test (FST)), acoustic startle response (ASR), and pre-pulse inhibition (PPI). The present results showed that Per2 knockout impacted CORT levels, mRNA expression, depressive-like behaviors, ASR and PPI. Unlike wild-type (WT) mice, Per2 knockout (Per2) mice showed no diurnal rise in CORT levels at the onset of the dark cycle. Per2−/− mice had enhanced CORT levels and adrenal melanocortin receptor 2 (Mc2R) mRNA expression following restraint. There were no changes in expression of any other pituitary or adrenal gene. In the FST, Per2−/− mice spent more time floating (less time struggling) than WT mice, suggesting increased depressive-like behaviors. Per2−/− mice had deficits in ASR and PPI startle responses compared to WT mice. In summary, these findings showed that disruption of the circadian system via Per2 gene deletion dysregulated the HPA stress axis and is subsequently correlated with increased depressive-like behaviors and deficits in startle response.

中文翻译：

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敲除昼夜节律基因 Per2 会破坏皮质酮分泌并导致抑郁样行为和惊吓反应缺陷

周期昼夜节律调节器 2 (Per2) 基因对于调节影响生物过程的昼夜节律很重要。下丘脑-垂体-肾上腺 (HPA) 轴的昼夜节律控制对于调节参与应激反应的激素至关重要。HPA 轴的失调与神经精神疾病有关。因此，了解昼夜节律的中断如何改变 HPA 轴非常重要。解决这个问题的一种方法是在动物模型中删除一个参与调节中央昼夜节律基因（如 Per2）的基因，并确定这种删除如何影响 HPA 轴和当 HPA 轴失调时改变的行为。为了研究这一点，通过从亮（非活动阶段）到暗（活动阶段）的过渡来测量皮质酮 (CORT) 水平。此外，在轻度束缚应激后测量 CORT 水平以及垂体和肾上腺 mRNA 表达。测试小鼠的抑郁样行为（强迫游泳测试 (FST)）、声学惊吓反应 (ASR) 和前脉冲抑制 (PPI)。目前的结果表明，Per2 敲除会影响 CORT 水平、mRNA 表达、抑郁样行为、ASR 和 PPI。与野生型 (WT) 小鼠不同，Per2 敲除 (Per2) 小鼠在黑暗周期开始时未显示 CORT 水平的昼夜升高。Per2-/- 小鼠在约束后的 CORT 水平和肾上腺黑皮质素受体 2 (Mc2R) mRNA 表达增加。任何其他垂体或肾上腺基因的表达没有变化。在 FST 中，Per2-/- 小鼠比 WT 小鼠花费更多的时间漂浮（更少的挣扎时间），表明抑郁样行为增加。与 WT 小鼠相比，Per2-/- 小鼠在 ASR 和 PPI 惊吓反应方面存在缺陷。总之，这些发现表明，通过 Per2 基因缺失破坏昼夜节律系统会使 HPA 应激轴失调，随后与增加的抑郁样行为和惊吓反应缺陷相关。