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. 2017 Aug 9;7:7711. doi: 10.1038/s41598-017-07394-3

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© The Author(s) 2017

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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Albumin induced the degradation of perineuronal nets around PV(+) interneurons and losartan attenuated the effect of albumin. (a) Experimental design. Intracerebroventricular (ICV) osmotic pumps containing albumin (0.4 mM) or aCSF were implanted in rats and mice and removed after 7 days. (b,c) Molecules involved in ECM remodeling including MMP9, TIMP1, and STAT3 were significantly increased in dissected rat hippocampi following albumin infusion for 7 days. Uncropped blot images are available in the Supplementary Fig. S4. Each group has four biological replicates. Unpaired student t- test. *p < 0.05, two-tailed. (d) Representative confocal images showing PNNs (WFA) and PV(+) cells in the mouse hippocampal CA1 region at 30 days post implantation. (e) A separate set of animals was infused with albumin + losartan (10μM) or aCSF + losartan. Scale bar = 50 μm. (f) Albumin exposure decreased the association of PNNs with PV(+) interneurons (*p < 0.05, **p < 0.01, ***p < 0.001, Two-way ANOVA, post-hoc Sidak’s test, two tailed). Co-administration of losartan attenuated the effect of albumin (p > 0.05, Mann-Whitney test, two-tailed). n.s., not significant. Each condition has three or four biological replicates (n = 3–4).