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. 2021 Aug 10;16:53. doi: 10.1186/s13024-021-00475-y

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© The Author(s) 2021

Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 6 — Pharmacological and genetic manipulation of KCCN channels promotes C9-ALS MNs survival and Drosophila locomotor function. A High content images of caspase 3 and MAP2 positive motor neurons from two control (MIFF1 & CS14) and two C9ORF&2-ALS (ALS-28 & ALS-29) lines. Scale bars: 50 μm. Bar charts represent the percentage of caspase 3 positive cells (top right) and of apoptotic cells measured by nuclear fragmentation (bottom right) in healthy and C9-ALS patient-derived motor neurons (mean ± SEM; one-way ANOVA Tukey’s multiple comparison test, ****: p < 0.0001; N (replicate experiments) = 3). B High-content microscopy automated imaging quantification of caspase-3 positive cells (%) treated with DMSO or increasing concentrations of the KCNN1/3 inhibitor apamin (APA) in healthy, C9-ALS and isogenic CRISPR-Cas9 mediated deletion of the repeat expansion (ISO) patient-derived motor neurons (mean ± SEM; two-way ANOVA Tukey’s multiple comparison test, ****: p < 0.0001; N (replicate experiments) = 3). C Larval crawling ability of male and female control (G4C3x3) or C9-ALS (G4C2x36) Drosophila crossed or not with two different SK mutant lines driven by nSyb-GAL4 (mean ± SEM; one-way ANOVA; ns: non-significant, *: p < 0.05, **: p < 0.01, ****: p < 0.0001; N (Drosophila larvae) > 5). D Climbing ability of male and female control (G4C3x3) or C9-ALS (G4C2x36) Drosophila crossed or not with two different SK mutant lines driven by D42-GAL4 (mean ± 95% CI; Kruskal-Wallis with Dunn’s correction; ns: non-significant, *: p < 0.05, **: p < 0.01, ****: p < 0.0001; N (Drosophila flies) > 25)