Background There has been much discussion recently about the occurrence of neuropsychological complications during the perioperative period. Diabetes is known to be one of the metabolic risk factors. Although the number of patients with diabetes mellitus (DM) has been increasing, the pathophysiology of postoperative neuropsychological dysfunction in DM patients is still unclear. Recently, a deficiency of neurotransmitters, such as monoamines, was reported to be associated with mental disorders. Therefore, we investigated the effects of surgical stress on behavioral activity and hippocampal noradrenaline (NA) level in type 2 diabetes mellitus model (T2DM) mice. Methods Eighty-four 6-week-old male C57BL/6J mice were divided into four groups (non-diabetes, non-diabetes with surgery, T2DM, and T2DM with surgery groups). T2DM mice were established by feeding a high-fat diet (HFD) for 8 weeks. At 14 weeks of age, fifteen mice in each group underwent a series of behavioral tests including an open field (OF) test, a novel object recognition (NOR) test and a light–dark (LD) test. In the surgery groups, open abdominal surgery with manipulation of the intestine was performed 24 h before the behavioral tests as a surgical stress. Hippocampal noradrenaline (NA) concentration was examined in six mice in each group by high-performance liquid chromatography. The data were analyzed by the Mann–Whitney U test, and p values less than 0.05 were considered significant. Results The T2DM group showed significantly increased explorative activity in the NOR test (P = 0.0016) and significantly increased frequency of transition in the LD test (P = 0.043) compared with those in the non-diabetic group before surgery. In T2DM mice, surgical stress resulted in decreased total distance in the OF test, decreased explorative activity in the NOR test, and decreased frequency of transition in the LD test (OF: P = 0.015, NOR: P = 0.009, LD: P = 0.007) and decreased hippocampal NA (P = 0.015), but such differences were not observed in the non-diabetic mice. Conclusions Mice with T2DM induced by feeding an HFD showed increased behavioral activities, and surgical stress in T2DM mice caused postoperative hypoactivity and reduction of the hippocampal NA level.

中文翻译：

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手术应激对2型糖尿病模型小鼠行为活动和海马去甲肾上腺素的抑制

背景 近期关于围手术期神经心理并发症的发生讨论较多。众所周知，糖尿病是代谢风险因素之一。尽管糖尿病（DM）患者的数量一直在增加，但DM患者术后神经心理功能障碍的病理生理机制尚不清楚。最近，据报道缺乏神经递质，如单胺类，与精神障碍有关。因此，我们研究了手术应激对 2 型糖尿病模型 (T2DM) 小鼠的行为活动和海马去甲肾上腺素 (NA) 水平的影响。方法 84只6周龄雄性C57BL/6J小鼠分为4组（非糖尿病组、非糖尿病手术组、T2DM组和T2DM手术组）。通过喂食高脂肪饮食 (HFD) 8 周来建立 T2DM 小鼠。在 14 周龄时，每组 15 只小鼠接受了一系列行为测试，包括开放场 (OF) 测试、新物体识别 (NOR) 测试和明暗 (LD) 测试。在手术组中，在行为测试前 24 小时进行开腹手术和肠道操作，作为手术压力。通过高效液相色谱法检测每组 6 只小鼠的海马去甲肾上腺素 (NA) 浓度。数据通过 Mann-Whitney U 检验进行分析，p 值小于 0.05 被认为是显着的。结果 T2DM 组在 NOR 测试中显示出显着增加的探索活动（P = 0.0016），在 LD 测试中显示出显着增加的转变频率（P = 0. 043) 与术前非糖尿病组比较。在 T2DM 小鼠中，手术应激导致 OF 测试中的总距离减少，NOR 测试中的探索活动减少，LD 测试中的转换频率降低（OF：P = 0.015，NOR：P = 0.009，LD：P = 0.007) 和海马 NA 降低 (P = 0.015)，但在非糖尿病小鼠中未观察到这种差异。结论 喂食 HFD 诱导的 T2DM 小鼠的行为活动增加，T2DM 小鼠的手术应激导致术后活动减退和海马 NA 水平降低。P = 0.007）和海马 NA 降低（P = 0.015），但在非糖尿病小鼠中未观察到这种差异。结论 喂食 HFD 诱导的 T2DM 小鼠的行为活动增加，T2DM 小鼠的手术应激导致术后活动减退和海马 NA 水平降低。P = 0.007）和海马 NA 降低（P = 0.015），但在非糖尿病小鼠中未观察到这种差异。结论 喂食 HFD 诱导的 T2DM 小鼠的行为活动增加，T2DM 小鼠的手术应激导致术后活动减退和海马 NA 水平降低。