Carregosa Diogo, Loncarevic-Vasiljkovic Natasa, Feliciano Raquel, Moura-Louro Diogo, Mendes César S, Dos Santos Cláudia Nunes
iNOVA4Health, NOVA Medical School | Faculdade Ciências Médicas, NMS|FCM, Universidade Nova de Lisboa, Campo dos Mártires da Pátria, Lisboa, Portugal.
iBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, Oeiras, Portugal.
J Inflamm (Lond). 2024 Oct 8;21(1):39. doi: 10.1186/s12950-024-00412-y.
Lipopolysaccharide (LPS) challenge in mice has been used to identify the mechanisms and therapeutics for neuroinflammation. In this study, we aimed to comprehensively evaluate the behavioral changes including locomotion, exploration, and memory, correlating them with a panel of thirteen inflammatory cytokines in both blood and brain.We found that acute LPS administration (0.83 mg/Kg i.p.) reduced body weight, food intake, and glucose levels compared to the saline-injected mice, concomitant with decreased activity in home cage monitoring. Locomotion was significantly reduced in Open Field, Introduced Object, and Y-Maze tests. Decreased exploratory behavior in the Y-Maze and Introduced Object tests was noticed, by measuring the number of arms explored and object interaction time, respectively. Additionally, in rotarod, LPS administration led to a significant decrease in the distance achieved, while in the MouseWalker, LPS led to a reduction in average velocity.LPS induced a decrease in microglia ramification index in the motor cortex and the striatum, while surprisingly a reduction in microglia number was observed in the motor cortex.The concentrations of thirteen cytokines in the blood were significantly altered, while only CXCL1, CCL22, CCL17, G-CSF, and IL-12p40 were changed in the brain. Correlations between cytokine levels in blood and brain were found, most notably for CCL17 and CCL22. TGFβ was the only one with negative correlations to other cytokines. Correlations between cytokines and behavior changes were also disclosed, especially for CCL17, CCL22, G-CSF, and IL-6 and negatively for TGFβ and IL-10.In summary, our study employing acute LPS challenge in mice has revealed a comprehensive profile of behavioral alterations alongside significant changes in inflammatory cytokine levels, both in peripheral blood and brain tissue. These findings contribute to a deeper understanding of the interplay between inflammation and behavior, with possible implications for identifying prognostics and therapeutic targets for neuroinflammatory conditions.
小鼠脂多糖（LPS）激发试验已被用于确定神经炎症的机制和治疗方法。在本研究中，我们旨在全面评估包括运动、探索和记忆在内的行为变化，并将其与血液和大脑中的一组13种炎性细胞因子相关联。我们发现，与注射生理盐水的小鼠相比，急性给予LPS（0.83 mg/Kg腹腔注射）可降低体重、食物摄入量和血糖水平，同时伴随着在笼内监测活动的减少。在旷场试验、新物体识别试验和Y迷宫试验中，运动能力显著降低。通过分别测量探索臂的数量和物体交互时间，发现Y迷宫试验和新物体识别试验中的探索行为减少。此外，在转棒试验中，给予LPS导致达到的距离显著减少，而在MouseWalker试验中，LPS导致平均速度降低。LPS诱导运动皮层和纹状体中小胶质细胞分支指数降低，而令人惊讶的是，在运动皮层中观察到小胶质细胞数量减少。血液中13种细胞因子的浓度发生了显著变化，而大脑中仅CXCL1、CCL22、CCL17、G-CSF和IL-12p40发生了变化。发现血液和大脑中细胞因子水平之间存在相关性，最显著的是CCL17和CCL22。TGFβ是唯一与其他细胞因子呈负相关的细胞因子。还揭示了细胞因子与行为变化之间的相关性，特别是CCL17、CCL22、G-CSF和IL-6，而TGFβ和IL-10呈负相关。总之，我们在小鼠中采用急性LPS激发试验的研究揭示了行为改变的全面概况以及外周血和脑组织中炎性细胞因子水平的显著变化。这些发现有助于更深入地理解炎症与行为之间的相互作用，可能对确定神经炎症性疾病的预后和治疗靶点具有重要意义。
