神经炎症与抑郁症的病理生理学相关。脓毒症相关脑病（SAE）引起的类抑郁行为的分子机制尚不完全了解。J147（姜黄素的类似物）被报道能改善记忆并具有神经保护作用，但其在SAE中引起的类抑郁行为的生物学功能尚不清楚。我们调查了J147对脂多糖（LPS）诱导的神经炎症、类抑郁行为以及小鼠海马和小胶质细胞（BV2）中的Toll样受体4（TLR4）/核因子-κB（NF-κB）信号通路的影响。强迫游泳实验（FST）和悬尾实验（TST）用于评估类抑郁行为。使用RT-qPCR和ELISA测量了前炎症基因白介素（IL）-6、IL-1β和肿瘤坏死因子（TNF）-α的表达。使用免疫荧光染色检测了小胶质细胞的激活。使用西方博鳌和免疫荧光染色研究了TLR4/NF-κB信号通路。J147预处理明显下调了小胶质细胞中IL-6、IL-1β和TNF-α的表达以及离子钙结合适配蛋白-1的平均荧光强度。J147抑制了LPS诱导的核因子κB（NF-κB）的核转位、核因子κB的抑制剂（IκB）降解以及小胶质细胞中的TLR4激活。J147给药抑制了LPS处理的小鼠体重下降、死亡、小胶质细胞激活和类抑郁行为。总之，J147通过减弱小胶质细胞中的TLR4/NF-κB信号通路，改善了由神经炎症引起的脓毒症诱导的类抑郁行为。©2023 作者。

Neuroinflammation is associated with the pathophysiology of depression. The molecular mechanism of depressive-like behavior caused by sepsis-associated encephalopathy (SAE) is incompletely understood. J147 (an analog of curcumin) has been reported to improve memory and has neuroprotective activity, but its biological function in the depressive-like behavior observed in SAE is not known. We investigated the effects of J147 on lipopolysaccharide (LPS)-induced neuroinflammatory, depressive-like behaviors, and the toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signal pathway in the mouse hippocampus and microglia (BV2 cells). The forced-swimming test (FST) and tail-suspension test (TST) were undertaken for assessment of depressive-like behaviors. Expression of the proinflammatory genes interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α were measured using RT-qPCR and ELISA. Microglia activation was detected using immunofluorescence staining. The TLR4/NF-κB signaling pathway was studied using western blotting and immunofluorescence staining. J147 pretreatment markedly downregulated expression of IL-6, IL-1β, and TNF-α, and the mean fluorescence intensity of ionized calcium-binding adapter protein-1 in microglia. J147 restrained LPS-induced nuclear translocation of nuclear factor-kappa B (NF-κB), inhibitor of nuclear factor kappa B (IκB) degradation, and TLR4 activation in microglia. J147 administration inhibited bodyweight loss, mortality, microglia activation, and depressive-like behaviors in LPS-treated mice. In conclusion, J147 ameliorated the sepsis-induced depressive-like behaviors induced by neuroinflammation through attenuating the TLR4/NF-κB signaling pathway in microglia.© 2023. The Author(s).