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. 2019 May 17;9:7562. doi: 10.1038/s41598-019-44006-8

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© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Systemic treatment with low dose LPS induces neurological and psychiatric illness with microglial activation. (a) Change of BW after systemic LPS administration. The transient loss, but not statistically significant, of BW in LPS-treated mice at day 3 after LPS administration is observed. BW of LPS-treated mice are recovered gradually. F (1, 110) = 0.754, p = 0.39. (b) Y-maze test for measuring short memory and working memory. The Y-maze score of LPS-treated mice is significantly poorer than that of sham-treated mice. The reduction of the Y-maze score continued during the experiment. F (1, 110) = 22.17, p < 0.0001. (c) WRA for evaluating activity and anxiety. The WRA score of LPS-treated mice is significantly reduced, during the experiment. F (1, 110) = 20.61, p < 0.0001. (d) RR test for evaluating motor coordination. The RR score of LPS-treated mice is significantly reduced after LPS treatment. F (1, 110) = 11.21, p < 0.001. (a–d; sham; n = 13, LPS; n = 15) (e–j) Microglial staining using Iba-1 antibody in the hippocampus. (e,f) In sham-treated mice, the density of Iba-1 signal is not high, and ramified-shaped microglia are observed at high magnification (arrows). (g,h) In the hippocampus from mice 2 days after LPS treatment, the Iba-1 signal is dense, and amoeboid-shaped microglia are observed at high magnification (arrowheads). (i,j) In the hippocampus from mice 15 days after LPS treatment, the Iba-1 signal is dense, and both amoeboid-shaped (arrowheads) and ramified-shaped microglia (arrows) are observed at high magnification. Time course analyses for (k) TNF-α, (l) IL-1β, and (m) IL-10. *p < 0.01 vs day 0 mice (sham-treated mice). TNF-α and IL-1β expression in the hippocampus and cerebral cortex are increased at 2 days after LPS treatment, followed by a gradual decrease. TNF-α and IL-1β expression in the cerebellum are mildly increased, but the increase is not statistically significant. IL-10 is mildly increased in the hippocampus, cerebral cortex, and cerebellum at 2 days after LPS treatment, but the increase is not statistically significant. (k–m; sham-treated; n = 7, LPS-treated 2 days; n = 7, LPS-treated 9 days; n = 3).