Lentivirus-mediated interleukin-1β (IL-1β) knock-down in the hippocampus alleviates lipopolysaccharide (LPS)-induced memory deficits and anxiety- and depression-like behaviors in mice

• Published in: Journal of neuroinflammation Vol. 14; no. 1; p. 190
• Main Authors: Li, Mengmeng, Li, Chenli, Yu, Hanjie, Cai, Xiongxiong, Shen, Xinbei, Sun, Xin, Wang, Jinting, Zhang, Yanhua, Wang, Chuang
• Format: Journal Article
• Language: English
• Published: England BioMed Central 20.09.2017; BMC
• Subjects: Animals; Anxiety; Anxiety - immunology; Anxiety - metabolism; Behavior, Animal - drug effects; Behavior, Animal - physiology; Depression; Depression - immunology; Depression - metabolism; Gene Knockdown Techniques; Hippocampus - immunology; Hippocampus - metabolism; Inflammation - chemically induced; Inflammation - complications; Interleukin-1beta - metabolism; Interleukin-1β (IL-1β); Lentivirus; Lipopolysaccharides (LPS); Lipopolysaccharides - toxicity; Male; Memory deficits; Memory Disorders - immunology; Memory Disorders - metabolism; Mice; Depression; Interleukin-1β (IL-1β); Anxiety; Memory deficits; Lipopolysaccharides (LPS)
• ISSN: 1742-2094; 1742-2094
• DOI: 10.1186/s12974-017-0964-9

Recent evidence has suggested that peripheral inflammatory responses induced by lipopolysaccharides (LPS) play an important role in neuropsychiatric dysfunction in rodents. Interleukin-1β (IL-1β), 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-1β may have a therapeutic benefit in the treatment of neuropsychiatric disorders. However, the precise underlying mechanism of knock-down of IL-1β in repairing behavioral changes by LPS remains unclear. The mice were treated with either IL-1β 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-1β, tumor necrosis factor (TNF-α), neuropeptide VGF (non-acronymic), and brain-derived neurotrophic factor (BDNF) were assayed. Our results demonstrated that IL-1β knock-down in the hippocampus significantly attenuated the memory deficits and anxiety- and depression-like behaviors induced by LPS in mice. In addition, IL-1β knock-down ameliorated the oxidative and neuroinflammatory responses and abolished the downregulation of VGF and BDNF induced by LPS. Collectively, our findings suggest that IL-1β is necessary for the oxidative and neuroinflammatory responses produced by LPS and offers a novel drug target in the IL-1β/oxidative/neuroinflammatory/neurotrophic pathway for treating neuropsychiatric disorders that are closely associated with neuroinflammation, oxidative stress, and the downregulation of VGF and BDNF.