重复施用低剂量脂多糖可改善重复社交失败应激诱发的行为异常和异常免疫反应

IF 5.2 3区 医学 Q1 NEUROSCIENCES
Vichuda Charoensaensuk, Wei-Lan Yeh, Bor-Ren Huang, Tsung-Che Hsu, Sheng-Yun Xie, Chao-Wei Chen, Yu-Wen Wang, Liang-Yo Yang, Cheng-Fang Tsai, Dah-Yuu Lu
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引用次数: 0

摘要

先天性免疫细胞重复暴露于阈下剂量的内毒素成分可能会调节炎症反应。然而,中枢神经系统(CNS)与免疫系统之间相互作用的调节机制仍不清楚。本研究旨在探讨脂多糖(LPS)预处理对重复社交失败应激(RSDS)诱导的异常免疫反应和行为障碍的影响。本研究旨在利用RSDS范式阐明重复给予阈下剂量LPS对行为损伤的保护作用的机制。LPS预处理改善了RSDS失能小鼠的异常行为,同时降低了单胺氧化酶,增加了海马中糖皮质激素受体的表达。此外,LPS预处理还能显著减少外周髓系细胞(CD11b+CD45hi),主要是循环炎性单核细胞(CD11b+CD45hiLy6ChiCCR2+)在RSDS挑战下进入大脑。重要的是,我们发现 LPS 预处理是通过调节小胶质细胞中脂钙蛋白-2(LCN2)的表达来发挥其保护作用的,LCN2 随后会诱导趋化因子 CCL2 和促炎细胞因子的表达。随后,LPS-预处理减少了RSDS缺陷小鼠大脑中的常驻小胶质细胞数量(CD11b+CD45intCCL2+)。此外,LPS 预处理还减轻了骨髓、脾脏和血液中与 RSDS 相关的白细胞(CD11b+CD45+CCR2+)和中性粒细胞(CD11b+CD45+Ly6G+)的表达。特别是,LPS 预处理还促进了海马中内源性抗氧化剂和抗炎蛋白的表达。我们的研究结果表明,LPS 预处理可改善脂钙蛋白 2 相关的小胶质细胞活化和异常免疫反应,促进内源性抗氧化剂和抗炎蛋白的表达,从而维持大脑和免疫系统中促炎症/抗炎症的平衡,最终保护小鼠免受 RSDS 引起的异常免疫反应和行为变化的影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Repetitive Administration of Low-Dose Lipopolysaccharide Improves Repeated Social Defeat Stress-Induced Behavioral Abnormalities and Aberrant Immune Response

Repetitive Administration of Low-Dose Lipopolysaccharide Improves Repeated Social Defeat Stress-Induced Behavioral Abnormalities and Aberrant Immune Response

Repetitive exposure of innate immune cells to a subthreshold dosage of endotoxin components may modulate inflammatory responses. However, the regulatory mechanisms in the interactions between the central nervous system (CNS) and the immune system remain unclear. This study aimed to investigate the effects of lipopolysaccharide (LPS) preconditioning in repeated social defeat stress (RSDS)-induced abnormal immune responses and behavioral impairments. This study aimed to elucidate the mechanisms that underlie the protective effects of repeated administration of a subthreshold dose LPS on behavioral impairments using the RSDS paradigm. LPS preconditioning improved abnormal behaviors in RSDS-defeated mice, accompanied by decreased monoamine oxidases and increased glucocorticoid receptor expression in the hippocampus. In addition, pre-treated with LPS significantly decreased the recruited peripheral myeloid cells (CD11b+CD45hi), mainly circulating inflammatory monocytes (CD11b+CD45hiLy6ChiCCR2+) into the brain in response to RSDS challenge. Importantly, we found that LPS preconditioning exerts its protective properties by regulating lipocalin-2 (LCN2) expression in microglia, which subsequently induces expressions of chemokine CCL2 and pro-inflammatory cytokine. Subsequently, LPS-preconditioning lessened the resident microglia population (CD11b+CD45intCCL2+) in the brains of the RSDS-defeated mice. Moreover, RSDS-associated expressions of leukocytes (CD11b+CD45+CCR2+) and neutrophils (CD11b+CD45+Ly6G+) in the bone marrow, spleen, and blood were also attenuated by LPS-preconditioning. In particular, LPS preconditioning also promoted the expression of endogenous antioxidants and anti-inflammatory proteins in the hippocampus. Our results demonstrate that LPS preconditioning ameliorates lipocalin 2-associated microglial activation and aberrant immune response and promotes the expression of endogenous antioxidants and anti-inflammatory protein, thereby maintaining the homeostasis of pro-inflammation/anti-inflammation in both the brain and immune system, ultimately protecting the mice from RSDS-induced aberrant immune response and behavioral changes.

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来源期刊
CiteScore
13.60
自引率
0.00%
发文量
18
审稿时长
6-12 weeks
期刊介绍: The aims of the Journal of Neuroimmune Pharmacology are to promote the dissemination, interest, and exchange of new and important discoveries for the pharmacology and immunology of the nervous system. The aims parallel that of the Society on NeuroImmune Pharmacology by increasing the fundamental understanding of neurologic and neuropsychiatric disorders affected by the immune system or vice versa and towards pharmacologic measures that lead, either to a better understanding of disease mechanisms, or by improving disease outcomes. The scope of JNIP includes all primary works and reviews into the etiology, prevention, and treatment of neuroimmune and nervous system diseases affected by disordered immunity. Original studies serving to define neuroimmune modulation of environmental or endogenous cues such as toxins and drugs of abuse, hormones, and cytokines are welcome. JNIP will serve as a reliable source of interdisciplinary information bridging the fields of pharmacology, immunology, and neuroscience.
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