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  2. Intranasal administration of lipopolysaccharide reverses chronic stress-induced depression-like behavior in mice by microglial stimulation

Intranasal administration of lipopolysaccharide reverses chronic stress-induced depression-like behavior in mice by microglial stimulation

  • Int Immunopharmacol. 2023 Jun 2;120:110347. doi: 10.1016/j.intimp.2023.110347.
Chao Huang 1 Ting Ye 2 Bingran Chen 2 Zhuo Chen 3 Ying Ye 4 Huijun Liu 5
Affiliations

Affiliations

  • 1 Department of Pharmacology, School of Pharmacy, Nantong University, #19 Qixiu Road, Nantong 226001, Jiangsu Province, China. Electronic address: huangchao@ntu.edu.cn.
  • 2 Department of Pharmacology, School of Pharmacy, Nantong University, #19 Qixiu Road, Nantong 226001, Jiangsu Province, China.
  • 3 Invasive Technology Department, Affiliated Hospital 2 of Nantong University, First People's Hospital of Nantong City, No. 6 Haierxiang North Road, Nantong 226001, China.
  • 4 Department of Ultrasound, Affiliated Hospital of Nantong University, #20 Xisi Road, Nantong 226001, Jiangsu, China.
  • 5 Department of Pharmacy, The First People's Hospital of Yancheng, Yancheng First Hospital, Affiliated Hospital of Nanjing University Medical School, #66 Renmin South Road, Yancheng 224006, Jiangsu, China. Electronic address: 493863893@qq.com.
Abstract

We recently reported that intraperitoneal injection of a low dose of lipopolysaccharide (LPS) reversed depression-like behavior in mice induced by chronic stress by stimulating microglia in the hippocampus. In this study, we found that a single intranasal administration of LPS at a dose of 5 or 10 μg/mouse, but not at a dose of 1 μg/mouse, rapidly reversed depression-like behavior in mice stimulated with chronic unpredictable stress (CUS). In the time-dependent experiment, a single intranasal administration of LPS (10 μg/mouse) reversed CUS-induced depression-like behavior in mice 5 and 8 h but not 3 h after drug administration. The antidepressant effect of a single intranasal LPS administration (10 μg/mouse) lasted at least 10 days and disappeared 14 days after administration. Fourteen days after the first intranasal LPS administration, a second intranasal LPS administration (10 μg/mouse) still reversed the increased immobility time in TST and FST and the decreased sucrose uptake in SPT in CUS mice, which again exhibited depression-like behaviors 5 h after LPS administration. The antidepressant effect of intranasal LPS administration was dependent on microglial activation, because inhibition of microglia by pretreatment with minocycline (40 mg/kg) or depletion of microglia by pretreatment with PLX3397 (290 mg/kg) prevented the antidepressant effect of intranasal LPS administration in CUS mice. These results suggest that stimulation of the microglia-mediated innate immune response by intranasal administration of LPS can produce rapid and sustained antidepressant effects in Animals under chronic stress conditions.

Keywords

Depression; Hippocampus; Innate immune response; Intranasal LPS administration.

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