Although several recent studies have suggested that neuroinflammation plays a role in depression, both medication and neuroinflammatory preventive strategies have been poorly investigated. Recent studies have indicated that preconditioning with lipopolysaccharide (LPS) reduces the damage that occurs following ischemic stroke and brain trauma. However, to date, the effects of LPS preconditioning on psychiatric symptoms have not been reported. Thus, we assessed gene expression and behavioral changes affected by preconditioning with low-dose (LD) LPS in male mice with systemic inflammation induced by administration of high-dose (HD) LPS. mRNA expression analyses of cytokine-, glial-, and oxidative stress-associated genes revealed that majority of these genes responded to HD LPS. Differential gene expression in the presence and absence of LD LPS preconditioning, identified a subset of genes that may contribute to the mechanism of LPS preconditioning in the brain. Notably, LPS preconditioning attenuated an increase in expression of the astrocyte marker Gfap caused by systemic inflammation, suggesting that astrocytes have a key role in endotoxin tolerance in the brain induced by LPS preconditioning. As increased astrocyte in the brain of patients with depression is suggested to contribute to the pathophysiology of major depression, LPS preconditioning might be applicable to the prevention and treatment of depression. Unfortunately, in this study, LPS preconditioning did not show a reversal effect on behavior decline due to high-dose LPS-induced systemic inflammation. Alternative aspects of behavioral changes should be assessed to identify behavioral components that are affected by LPS preconditioning. Nonetheless, the findings in the present study indicate the possibility of the mechanism of endotoxin tolerance induction in the brain via astrocyte regulation by LPS preconditioning. Since there has been reported pharmacological significance of astrocytes in psychiatric disorders, regulation of endotoxin tolerance might be a key method to control psychiatric symptoms.

尽管最近的几项研究表明神经炎症在抑郁症中起作用，但对药物和神经炎症预防策略的研究很少。最近的研究表明，脂多糖 (LPS) 预处理可减少缺血性中风和脑外伤后发生的损伤。然而，迄今为止，尚未报道 LPS 预处理对精神症状的影响。因此，我们评估了因施用高剂量 (HD) LPS 引起全身炎症的雄性小鼠中受低剂量 (LD) LPS 预处理影响的基因表达和行为变化。细胞因子、神经胶质和氧化应激相关基因的 mRNA 表达分析表明，这些基因中的大多数对 HD LPS 有反应。在存在和不存在 LD LPS 预处理的情况下的差异基因表达，确定了可能有助于大脑中 LPS 预处理机制的基因子集。值得注意的是，LPS 预处理减弱了星形胶质细胞标志物表达的增加GFAP由全身炎症引起，表明星形胶质细胞在 LPS 预处理诱导的大脑内毒素耐受中起关键作用。由于抑郁症患者大脑中星形胶质细胞的增加被认为有助于重度抑郁症的病理生理学，LPS预处理可能适用于抑郁症的预防和治疗。不幸的是，在这项研究中，由于高剂量 LPS 引起的全身炎症，LPS 预处理并未显示出对行为下降的逆转作用。应评估行为变化的替代方面，以确定受 LPS 预处理影响的行为成分。尽管如此，本研究的结果表明，LPS 预处理通过星形胶质细胞调节在大脑中诱导内毒素耐受的机制可能存在。