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. 2018 Oct 3;23(10):2090–2110. doi: 10.1038/s41380-018-0253-8

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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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Fig. 4 — PQBP1 rescues synapse and cognitive function in AD mouse models. a Image processing used for quantification of spine numbers and figure presentation. Leftward process is generally used for generating spine images, while rightward process was employed in this study to quantify spine numbers and other parameters. Both of the final images were checked in regard of the spine identity. b Two-photon microscopic observation of dendritic spines in Synapsin-Cre male mice (SynCre XY), PQBP1-Floxed male mice (PQBP1-Floxed XY), and Synapsin-Cre PQBP1-cKO male mice (Syn-Cre PQBP1-cKO XY) are shown. c Quantitative analysis (3 mice in each group, 8–12 dendrites/mouse, Tukey’s HSD test) revealed that dendritic spines (protrusions) were lower in PQBP1-deficient mature neurons. d Live-imaging of dendritic spines with two-photon microscopy was performed for 24 h in three genotypes of mice. Newly formed spines are indicated with red arrowheads, eliminated spines are indicated with yellow arrowheads. e Quantitative analyses of dendritic protrusions revealed that formation of spines was lower in Synapsin-Cre PQBP1-cKO mice (3 mice in each group, 8–12 dendrites/mouse, Tukey’s HSD test). f AAV-PQBP1 mediated rescue of synapse pathology in 5xFAD male and APP-KI male mice. The mice received a single injection of AAV-PQBP1 into RSD at 5.5 months and were evaluated 2 weeks later at 6 months of age. g Two-photon microscopic images of dendritic spines in the first layer of RSD in 5xFAD or B6/SJL male mice after injection of AAV-EGFP or AAV-PQBP1. The right graph shows the quantitative analysis of spine number. h Two-photon microscopic images of contact of axon terminals and dendritic spines in the first layer of RSD in 5xFAD male mice after injection of AAV-Vamp-Cherry with AAV-EGFP or AAV-PQBP1. The right graph shows the quantitative analysis of the axon terminals merged on the spine. i Alteration ratios in the Y-maze test of 5xFAD male mice after injection of AAV-EGFP or AAV-PQBP1 are shown. j. Two-photon microscopic images of dendritic spines in the first layer of RSD in APP-KI or B6 male mice after injection of AAV-EGFP or AAV-PQBP1. The right graph shows the quantitative analysis of spine number. k Two-photon microscopic images of contact of axon terminals and dendritic spines in the first layer of RSD in APP-KI or B6 male mice after injection of AAV-Vamp-Cherry with AAV-EGFP or AAV-PQBP1. The right graph shows the quantitative analysis of the axon terminals merged on the spine. l Alteration ratios in the Y-maze test of APP-KI male mice after injection of AAV-EGFP or AAV-PQBP1 are shown