Fig. 6: GSK reduces UPR activation and poly(GA) levels in C9 CO slices.

a, WB image of CO slice samples at 220 DIV after immersion in medium for 12 h of GSK treatment with or without SA for 2 h. WB bands represent p-EIF2α, EIF2α and β-actin protein levels (upper) with quantification of p-EIF2α/EIF2α band density ratios after normalization to β-actin and to untreated C9-L1 controls in each blot (lower). Data are expressed as the mean ± s.e.m.; n = 3 independent CO slices; two-tailed unpaired t-test. b, Upper: dot blots show anti-poly(GA) immunoreactivity in C9-L1 versus H-L1 CO slice samples at 240 DIV and C9-L2 versus ISO-L2 CO slice samples at 200 DIV with or without (No Tx) a 14-day-long GSK or vehicle (Veh) treatment. Lower: scatter plots represent individual values of normalized blot densities to β-actin; n = 3 control–treatment CO slice-pairs from 3 independent organoids; two-tailed paired t-test. c, Representative immunofluorescence confocal superimposed z-stack images showing CTIP2+ neuronal nuclei (red) with perinuclear poly(GA) foci (green; arrows) and GFAP+ astroglia (cyan) overlapped with DAPI staining for three biological repeats per group. Orthogonal views (x–z) represent single confocal reconstructed planes. Scale bars, 10 μm for all images (2 μm for insets). See Supplementary Table 3 for detailed statistics and source data for unprocessed WB images.