Department of Pharmacy, Changzhou Geriatric Hospital Affiliated to Soochow University, Changzhou No.7 People's Hospital, Changzhou, Jiangsu, China.
Department of Pharmacology, School of Pharmacy, Nantong University, Nantong, Jiangsu, China.
Int J Neuropsychopharmacol. 2022 May 27;25(5):399-411. doi: 10.1093/ijnp/pyab097.
Our recent studies reported that a single injection with lipopolysaccharide (LPS) before stress exposure prevents depression-like behaviors in stressed mice. Monophosphoryl lipid A (MPL) is a derivative of LPS that lacks the undesirable properties of LPS. We hypothesize that MPL can exert a prophylactic effect on depression.
The experimental mice were pre-injected with MPL before stress exposure. Depression in mice was induced through chronic social defeat stress (CSDS). Behavioral tests were conducted to identify depression-like behaviors. Real-time polymerase chain reaction and biochemical assays were performed to examine the gene and protein expression levels of pro-inflammatory cytokines.
A single MPL injection 1 day before stress exposure at the dosages of 400, 800, and 1600 μg/kg but not 200 μg/kg prevented CSDS-induced depression-like behaviors in mice. This effect of MPL, however, vanished with the extension of the interval time between drug injection and stress exposure from 1 day or 5 days to 10 days, which was rescued by a second MPL injection 10 days after the first MPL injection or by a 4× MPL injection 10 days before stress exposure. A single MPL injection (800 μg/kg) before stress exposure prevented CSDS-induced increases in the gene expression levels of pro-inflammatory cytokines in the hippocampus and prefrontal cortex. Pre-inhibiting the innate immune stimulation by minocycline pretreatment (40 mg/kg) abrogated the preventive effect of MPL on CSDS-induced depression-like behaviors and neuroinflammatory responses in animal brains.
MPL, through innate immune stimulation, prevents stress-induced depression-like behaviors in mice by preventing neuroinflammatory responses.
我们最近的研究报告称，在应激暴露前注射一次脂多糖（LPS）可预防应激小鼠出现抑郁样行为。单磷酰脂质 A（MPL）是 LPS 的衍生物，缺乏 LPS 的不良特性。我们假设 MPL 可以对抑郁产生预防作用。
实验小鼠在应激暴露前预先注射 MPL。通过慢性社会挫败应激（CSDS）诱导小鼠抑郁。进行行为测试以确定抑郁样行为。进行实时聚合酶链反应和生化测定，以检查促炎细胞因子的基因和蛋白表达水平。
应激暴露前 1 天以 400、800 和 1600μg/kg 但不是 200μg/kg 的剂量单次注射 MPL 可预防 CSDS 诱导的小鼠抑郁样行为。然而，随着药物注射和应激暴露之间的间隔时间从 1 天或 5 天延长至 10 天，这种 MPL 效应消失了，第二次 MPL 注射或 10 天前进行 4×MPL 注射可挽救这种效应。应激暴露前 1 天单次注射 800μg/kg 的 MPL 可预防 CSDS 诱导的海马和前额叶皮质中促炎细胞因子基因表达水平的增加。预先用米诺环素预处理抑制先天免疫刺激（40mg/kg）可消除 MPL 对 CSDS 诱导的抑郁样行为和动物大脑神经炎症反应的预防作用。
MPL 通过先天免疫刺激，通过预防神经炎症反应，预防应激诱导的小鼠抑郁样行为。
