In this study, we investigated lipopolysaccharide (LPS)-induced cognitive impairment and neuroinflammation in C57BL/6J mice by using behavioral tests, immunofluorescence, enzyme-linked immunosorbent assay (ELISA) and Western blot. We found that LPS treatment leads to sickness behavior and cognitive impairment in mice as shown in the Morris water maze and passive avoidance test, and these effects were accompanied by microglia activation (labeled by ionized calcium binding adaptor molecule-1, IBA-1) and neuronal cell loss (labeled by microtubule-associated protein 2, MAP-2) in the hippocampus. The levels of interleukin-4 (IL-4) and interleukin-10 (IL-10) in the serum and brain homogenates were reduced by the LPS treatment, while the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), prostaglandin E2 (PGE 2 ) and nitric oxide (NO) were increased. In addition, LPS promoted the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in the brain homogenates. The Western blot analysis showed that the nuclear factor kappa B (NF-κB) signaling pathway was activated in the LPS groups. Furthermore, VIPER, which is a TLR-4-specific inhibitory peptide, prevented the LPS-induced neuroinflammation and cognitive impairment. These data suggest that LPS induced cognitive impairment and neuroinflammation via microglia activation by activating the NF-kB signaling pathway; furthermore, we compared the time points, doses, methods and outcomes of LPS administration between intraperitoneal and intracerebroventricular injections of LPS in LPS-induced neuroinflammation and cognitive impairment, and these data may provide additional insight for researchers performing neuroinflammation research.

A therosclerosis is the underlying cause of cardiovascular disease (CVD), which is the leading cause of mortality worldwide.1 CVD is initiated by the accumulation of lipids, necrotic cells, and fibrous elements in the neointima of medium and large arteries. 2,3 The primary cells that contribute to atherosclerotic lesion formation are endothelial cells, vascular smooth muscle cells, and macrophages. [4][5][6] Plaque formation results from the infiltration of circulating monocytes in the subendothelial space, where they differentiate into macrophages and subsequently internalize modified lipoproteins and further differentiate into foam cells. 7 Therefore, further clarification of the mechanisms leading to macrophage accumulation is important to prevent plaque rupture and subsequent life-threatening clinical complications, such as myocardial infarction and stroke. See accompanying editorial on page 7The nuclear receptor superfamily is composed of transcription factors that positively and negatively regulate gene expression, which not only influence lipid metabolism at the systemic level but also regulate lipid homeostasis and inflammation in macrophages, endothelial cells, and smooth muscle cells within the arterial walls. 8,9 The nuclear factor I (NFI) family of site-specific DNA-binding proteins are critical regulators of gliogenesis in the developing central nervous system.10,11 NFIA, a member of the NFI family, can modulate DNA replication and transcription through binding to duplex DNA containing the TTGGC motif or 5′-TTGGCN 5 GCCAA-3′ consensus sequence. 12 Many studies have shown that NFIA plays critical roles in specifying glial cell identity and promoting astrocyte differentiation during embryonic development. 10,11 In addition, a recent study demonstrated that NFIA was functionally required for proper adipocyte differentiation and lipid droplet formation. Overexpression of NFIA in 3T3-L1 cells could significantly result in lipid droplet formation without differentiation stimulus. Overexpression of dominantnegative NFIA or small interfering RNA (siRNA)-mediated knockdown of NFIA could markedly inhibit lipid accumulation during differentiation 13 . However, no publication has © 2014 American Heart Association, Inc. Objective-Cardiovascular disease caused by atherosclerosis is the number one cause of death in Western countries and threatens to become the major cause of morbidity and mortality worldwide. Long noncoding RNAs are emerging as new players in gene regulation, but how long noncoding RNAs operate in the development of atherosclerosis remains unclear. Approach and Results-Using microarray analysis, we found that long noncoding RNA RP5-833A20.1 expression was upregulated, whereas nuclear factor IA (NFIA) expression was downregulated in human acute monocytic leukemia macrophage-derived foam cells. Moreover, we showed that long noncoding RNA RP5-833A20.1 may decreases NFIA expression by inducing hsa-miR-382-5p expression in vitro. We found that the RP5-833A20.1/hsa-miR-382-5p/NFIA pathway is essenti...

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