NLRP3 INFLAMMASOME ACTIVATION CONTRIBUTES TO LONG-TERM BEHAVIORAL ALTERATIONS IN MICE INJECTED WITH LIPOPOLYSACCHARIDE

被引:110
作者
Zhu, Wei [1 ,2 ]
Cao, Feng-Sheng [3 ]
Feng, Jun [1 ]
Chen, Hua-Weng [1 ]
Wan, Jie-Ru [2 ]
Lu, Qing [4 ]
Wang, Jian [2 ]
机构
[1] Huazhong Univ Sci & Technol, Tongji Hosp, Dept Emergency Med, Tongji Med Coll, Wuhan, Hubei, Peoples R China
[2] Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, 720 Rutland Ave,Ross Bldg 37013, Baltimore, MD 21205 USA
[3] Xiangyang Cent Hosp, Dept Emergency Med, Xiangyang, Hubei, Peoples R China
[4] Huazhong Univ Sci & Technol, Sch Basic Med, Dept Pharmacol, Tongji Med Coll, 13 Hangkong Rd, Wuhan 430030, Hubei, Peoples R China
基金
美国国家卫生研究院;
关键词
depression; NLRP3; inflammasome; recognition memory; LPS; tail suspension test; forced swim test; DEPRESSION-LIKE BEHAVIOR; CHRONIC MILD STRESS; INTRACEREBRAL HEMORRHAGE; MOUSE MODEL; SEPSIS; BRAIN; INHIBITION; EXPRESSION; PROTECTS; ANXIETY;
D O I
10.1016/j.neuroscience.2016.11.037
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Lipopolysaccharide (LPS) might affect the central nervous system by causing neuroinflammation, which subsequently leads to brain damage and dysfunction. In this study, we evaluated the role of nod-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome activation in long-term behavioral alterations of 8-week-old male C57BL/6 mice injected intraperitoneally with LPS (5 mg/kg). At different time points after injection, we assessed locomotor function with a 24-point neurologic deficit scoring system and the rotarod test; assessed recognition memory with the novel object recognition test; and assessed emotional abnormality (anhedonia and behavioral despair) with the tail suspension test, forced swim test, and sucrose preference test. We also assessed protein expression of NLRP3, apoptosis-associated speck-like protein (ASC), and caspase-1 p10 in hippocampus by Western blotting; measured levels of interleukin (IL)-1 beta, IL-18, tumor necrosis factor alpha(TNF alpha), and IL-10 in hippocampus; measured TNF alpha and IL-1 beta in serum by ELISA; and evaluated microglial activity in hippocampus by lba1 immunofluorescence. We found that LPS-injected mice displayed long-term depression-like behaviors and recognition memory deficit; elevated expression of NLRP3, ASC, and caspase-1 p10; increased levels of IL-1 beta, IL-18, and TNF alpha; decreased levels of IL-10; and increased microglial activation. These effects were blocked by the NLRP3 inflammasome inhibitor Ac-Tyr-Val-Ala-Asp-chloromethylketone. The results demonstrate proof of concept that NLRP3 inflammasome activation contributes to long-term behavioral alterations in LPS-exposed mice, probably through enhanced inflammation, and that NLRP3 inflammasome inhibition might alleviate peripheral and brain inflammation and thereby ameliorate long-term behavioral alterations in LPS-exposed mice. (C) 2016 IBRO. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:77 / 84
页数:8
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