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

被引：0

作者：

Charoensaensuk, Vichuda ^{[1
]}

Yeh, Wei-Lan ^{[2
,3
]}

Huang, Bor-Ren ^{[4
,5
]}

Hsu, Tsung-Che ^{[6
]}

Xie, Sheng-Yun ^{[1
]}

Chen, Chao-Wei ^{[3
]}

Wang, Yu-Wen ^{[7
]}

Yang, Liang-Yo ^{[8
,9
,10
]}

Tsai, Cheng-Fang ^{[11
]}

Lu, Dah-Yuu ^{[1
]}

机构：

[1] China Med Univ, Sch Med, Dept Pharmacol, Taichung, Taiwan

[2] China Med Univ, Sch Med, Dept Biochem, Taichung 40402, Taiwan

[3] China Med Univ, Inst New Drug Dev, Taichung, Taiwan

[4] Taichung Tzu Chi Hosp, Buddhist Tzu Chi Med Fdn, Dept Neurosurg, Taichung, Taiwan

[5] Tzu Chi Univ, Sch Med, Hualien, Taiwan

[6] China Med Univ, Sch Med, Taichung 40402, Taiwan

[7] Yuanpei Univ Med Technol, Dept Biotechnol & Pharmaceut Technol, Hsinchu, Taiwan

[8] China Med Univ, Sch Med, Dept Physiol, Taichung 404328, Taiwan

[9] China Med Univ Taiwan, Grad Inst Biomed Sci, Taichung, Taiwan

[10] China Med Univ Hosp, Lab Neural Repair, Taichung 404327, Taiwan

[11] Asia Univ, Dept Med Lab Sci & Biotechnol, Taichung, Taiwan

来源：

JOURNAL OF NEUROIMMUNE PHARMACOLOGY | 2024年 / 19卷 / 01期

关键词：

Chemokine; Lipocalin-2; LPS tolerance; RSDS; Microglia; RECEPTOR MESSENGER-RNA; CENTRAL-NERVOUS-SYSTEM; MICROGLIAL ACTIVATION; SIGNAL-TRANSDUCTION; INFLAMMATION; ANXIETY; BRAIN; LIPOCALIN-2; EXPRESSION; DEPRESSION;

D O I：

10.1007/s11481-024-10141-x

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

引用

页数：21

共 72 条

[41] Cytokines sing the blues: inflammation and the pathogenesis of depression [J].