Department of Pharmacology, School of Pharmacy, Nantong University, #19 Qixiu Road, Nantong 226001, Jiangsu, China.
Department of Neurology, The People's Hospital of Danyang, Affiliated Danyang Hospital of Nantong University, Danyang, China.
Int Immunopharmacol. 2022 Oct;111:109126. doi: 10.1016/j.intimp.2022.109126. Epub 2022 Aug 13.
It has been reported that pre-stimulation of the innate immune system can prevent depressive and anxiogenic-like behaviors in chronically stressed male mice. However, it is unclear whether similar effects can be observed in female animals. In the present study, we investigated this question in female mice. Our results showed that a single injection of lipopolysaccharide (LPS; 100 μg/kg) one day before stress exposure prevented increased immobility time in the tail suspension test and forced swimming test and decreased sucrose intake in the sucrose preference test in chronic unpredictable stress (CUS)-treated female mice. The single LPS pre-injection (100 μg/kg) prevented the CUS-induced decrease in (i) time spent in open arms and number of entries into open arms in the elevated plus maze test, (ii) time spent in lit side in the light-dark test, and (iii) time spent in the central region of the open field in the open field test, along with no changes in locomotor activity. It was also found that the single LPS pre-injection in female mice prevented the CUS-induced increase in the expression levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 mRNA in the hippocampus and medial prefrontal cortex. Inhibition of innate immune system stimulation by minocycline pretreatment abrogated the preventive effect of LPS on CUS-induced depressive and anxiogenic-like behaviors and neuroinflammatory responses in the hippocampus and medial prefrontal cortex in female mice. These results suggest that pre-stimulation of the innate immune system by LPS injection may prevent the development of behavioral abnormalities in female mice.
据报道，预先刺激固有免疫系统可以预防慢性应激雄性小鼠的抑郁和焦虑样行为。然而，在雌性动物中是否能观察到类似的效果尚不清楚。在本研究中，我们在雌性小鼠中研究了这个问题。我们的结果表明，在应激暴露前一天注射一次脂多糖（LPS；100μg/kg）可预防慢性不可预测应激（CUS）处理的雌性小鼠在悬尾试验和强迫游泳试验中不动时间增加，以及在蔗糖偏好试验中蔗糖摄入减少。单次 LPS 预处理（100μg/kg）可预防 CUS 诱导的以下变化：（i）高架十字迷宫试验中进入开放臂的时间和次数减少，（ii）明暗试验中亮侧时间减少，（iii）旷场试验中中央区域时间减少，而运动活动没有变化。还发现，单次 LPS 预处理可预防 CUS 诱导的雌性小鼠海马和内侧前额叶皮质中肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和白细胞介素-6 mRNA 表达水平的增加。米诺环素预处理抑制固有免疫系统刺激可消除 LPS 对 CUS 诱导的雌性小鼠海马和内侧前额叶皮质中抑郁和焦虑样行为及神经炎症反应的预防作用。这些结果表明，LPS 注射预先刺激固有免疫系统可能预防雌性小鼠行为异常的发生。
