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. 2018 Sep 7;8:13438. doi: 10.1038/s41598-018-31680-3

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© The Author(s) 2018

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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PICK1 inhibition stabilizes surface GluA2 and attenuates Aβ-mediated increase in intracellular calcium concentration. (A–C) PICK1 inhibitor stabilizes surface AMPA receptors. (A) Cultured hippocampal neurons were untreated (left) or treated with the PICK1 inhibitor 1z (BIO922, 3 μM) (right) for 24 hours, and immunostained for surface GluA2. Scale bar, 20 μm (B), Histograms show quantification of surface GluA2 immunofluorescence intensity normalized to control (non-treated) values. n = 15 control, n = 15 (1z, BIO922) treated (P < 0.005). (C) Histograms show quantification of staining intensities of surface GluA2 in wild-type and PICK1 KO mice neurons normalized to the wild-type group n = 16 wild-type, n = 18 PICK1 KO (*P < 0.05). (D,E) PICK1 inhibitor blocks Aβ42-induced increase in intracellular calcium concentration. (D) AMPA receptor-dependent calcium influx was measured in cultured hippocampal neurons left untreated (control), or treated with Aβ42 in the absence (Aβ42) or presence of PICK1 inhibitor (Aβ42 + 1z, BIO922). (E) Histograms show quantification of intracellular calcium concentration normalized to control (non-treated) values comparing Aβ42-treated with Aβ42 + 1z-treated cells (*P < 0.05). (F) Structure of compound 1z, BIO922.