PMID- 28931410 OWN - NLM STAT- MEDLINE DCOM- 20180529 LR - 20181113 IS - 1742-2094 (Electronic) IS - 1742-2094 (Linking) VI - 14 IP - 1 DP - 2017 Sep 20 TI - Lentivirus-mediated interleukin-1beta (IL-1beta) knock-down in the hippocampus alleviates lipopolysaccharide (LPS)-induced memory deficits and anxiety- and depression-like behaviors in mice. PG - 190 LID - 10.1186/s12974-017-0964-9 [doi] LID - 190 AB - BACKGROUND: Recent evidence has suggested that peripheral inflammatory responses induced by lipopolysaccharides (LPS) play an important role in neuropsychiatric dysfunction in rodents. Interleukin-1beta (IL-1beta), a pro-inflammatory cytokine, has been proposed to be a key mediator in a variety of behavioral dysfunction induced by LPS in mice. Thus, inhibition of IL-1beta may have a therapeutic benefit in the treatment of neuropsychiatric disorders. However, the precise underlying mechanism of knock-down of IL-1beta in repairing behavioral changes by LPS remains unclear. METHODS: The mice were treated with either IL-1beta shRNA lentivirus or non-silencing shRNA control (NS shRNA) lentivirus by microinjection into the dentate gyrus (DG) regions of the hippocampus. After 7 days of recovery, LPS (1 mg/kg, i.p.) or saline was administered. The behavioral task for memory deficits was conducted in mice by the novel object recognition test (NORT), the anxiety-like behaviors were evaluated by the elevated zero maze (EZM), and the depression-like behaviors were examined by the sucrose preference test (SPT) and the forced swimming test (FST). Furthermore, the levels of malondialdehyde (MDA), superoxide dismutase (SOD), nuclear factor erythroid-derived 2-like 2 (Nrf2), heme oxygenase 1 (HO1), IL-1beta, tumor necrosis factor (TNF-alpha), neuropeptide VGF (non-acronymic), and brain-derived neurotrophic factor (BDNF) were assayed. RESULTS: Our results demonstrated that IL-1beta knock-down in the hippocampus significantly attenuated the memory deficits and anxiety- and depression-like behaviors induced by LPS in mice. In addition, IL-1beta knock-down ameliorated the oxidative and neuroinflammatory responses and abolished the downregulation of VGF and BDNF induced by LPS. CONCLUSIONS: Collectively, our findings suggest that IL-1beta is necessary for the oxidative and neuroinflammatory responses produced by LPS and offers a novel drug target in the IL-1beta/oxidative/neuroinflammatory/neurotrophic pathway for treating neuropsychiatric disorders that are closely associated with neuroinflammation, oxidative stress, and the downregulation of VGF and BDNF. FAU - Li, Mengmeng AU - Li M AD - Ningbo Key Laboratory of Behavioral Neuroscience, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang, 315211, People's Republic of China. AD - Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang, 315211, People's Republic of China. AD - Department of Physiology and Pharmacology, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang, 315211, People's Republic of China. FAU - Li, Chenli AU - Li C AD - Ningbo Key Laboratory of Behavioral Neuroscience, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang, 315211, People's Republic of China. AD - Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang, 315211, People's Republic of China. AD - Department of Physiology and Pharmacology, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang, 315211, People's Republic of China. FAU - Yu, Hanjie AU - Yu H AD - Ningbo Key Laboratory of Behavioral Neuroscience, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang, 315211, People's Republic of China. AD - Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang, 315211, People's Republic of China. AD - Department of Physiology and Pharmacology, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang, 315211, People's Republic of China. FAU - Cai, Xiongxiong AU - Cai X AD - Ningbo Key Laboratory of Behavioral Neuroscience, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang, 315211, People's Republic of China. AD - Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang, 315211, People's Republic of China. AD - Department of Physiology and Pharmacology, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang, 315211, People's Republic of China. FAU - Shen, Xinbei AU - Shen X AD - Ningbo Key Laboratory of Behavioral Neuroscience, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang, 315211, People's Republic of China. AD - Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang, 315211, People's Republic of China. AD - Department of Physiology and Pharmacology, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang, 315211, People's Republic of China. FAU - Sun, Xin AU - Sun X AD - Ningbo Key Laboratory of Behavioral Neuroscience, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang, 315211, People's Republic of China. AD - Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang, 315211, People's Republic of China. AD - Department of Physiology and Pharmacology, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang, 315211, People's Republic of China. FAU - Wang, Jinting AU - Wang J AD - Ningbo Key Laboratory of Behavioral Neuroscience, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang, 315211, People's Republic of China. AD - Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang, 315211, People's Republic of China. AD - Department of Physiology and Pharmacology, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang, 315211, People's Republic of China. FAU - Zhang, Yanhua AU - Zhang Y AD - Ningbo Key Laboratory of Behavioral Neuroscience, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang, 315211, People's Republic of China. AD - Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang, 315211, People's Republic of China. AD - Department of Physiology and Pharmacology, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang, 315211, People's Republic of China. FAU - Wang, Chuang AU - Wang C AUID- ORCID: 0000-0002-3816-230X AD - Ningbo Key Laboratory of Behavioral Neuroscience, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang, 315211, People's Republic of China. wanglovechuang@163.com. AD - Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang, 315211, People's Republic of China. wanglovechuang@163.com. AD - Department of Physiology and Pharmacology, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang, 315211, People's Republic of China. wanglovechuang@163.com. AD - Li Dak Sum Yip Yio Chin Kenneth Li Marine Biopharmaceutical Research Center, Ningbo University, Ningbo, 315211, People's Republic of China. wanglovechuang@163.com. LA - eng PT - Journal Article DEP - 20170920 PL - England TA - J Neuroinflammation JT - Journal of neuroinflammation JID - 101222974 RN - 0 (Interleukin-1beta) RN - 0 (Lipopolysaccharides) SB - IM MH - Animals MH - Anxiety/immunology/metabolism MH - Behavior, Animal/drug effects/*physiology MH - Depression/immunology/metabolism MH - Gene Knockdown Techniques MH - Hippocampus/*immunology/*metabolism MH - Inflammation/chemically induced/*complications MH - Interleukin-1beta/*metabolism MH - Lentivirus MH - Lipopolysaccharides/toxicity MH - Male MH - Memory Disorders/immunology/metabolism MH - Mice PMC - PMC5607621 OTO - NOTNLM OT - Anxiety OT - Depression OT - Interleukin-1beta (IL-1beta) OT - Lipopolysaccharides (LPS) OT - Memory deficits COIS- ETHICS APPROVAL: All animal experiments were approved by the Experimental Animal Ethics Committee of Ningbo University. CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2017/09/22 06:00 MHDA- 2018/05/31 06:00 PMCR- 2017/09/20 CRDT- 2017/09/22 06:00 PHST- 2017/06/07 00:00 [received] PHST- 2017/09/14 00:00 [accepted] PHST- 2017/09/22 06:00 [entrez] PHST- 2017/09/22 06:00 [pubmed] PHST- 2018/05/31 06:00 [medline] PHST- 2017/09/20 00:00 [pmc-release] AID - 10.1186/s12974-017-0964-9 [pii] AID - 964 [pii] AID - 10.1186/s12974-017-0964-9 [doi] PST - epublish SO - J Neuroinflammation. 2017 Sep 20;14(1):190. doi: 10.1186/s12974-017-0964-9.