Fig. 10: Exposure of SORCS2-deficient astrocytes to Aβ induces expression of δ secretase in neuroblastoma cells in trans.

a Experimental setup for co-culture model of primary astrocytes and SH-SY5Y cells, exposed to Aβ stress. SH-SY5Y cells (bottom well) were co-cultured with primary murine WT or KO astrocytes (in insets). The co-cultures were incubated in medium containing Aβ or control medium. The corresponding response in δ secretase transcript and protein levels was determined in both cell types. b Representative Western blot analyses, and densitometric quantification of replicate blots thereof, document levels of δ secretase in the lysates obtained from WT and KO astrocytes treated as described in (a). Detection of β-actin served as loading control. Data are expressed as relative to WT Aβ- (set to 1) and given as mean ± SEM from n = 6 biological replicates. Two-Way ANOVA with Uncorrected Fisher´s LSD. c Levels of Lgmn transcripts as determined by qRT-PCR in primary WT and KO astrocytes treated with control (-) or Aβ-conditioned media (+) for 24 h. Data are expressed as relative expression levels (set to 1 for WT Aβ-) and given as mean ± SEM from n = 11 (WT), n = 12 (KO Aβ+), n = 13 (KO Aβ-) biological replicates per group. d Representative Western blot analyses, and densitometric quantification of replicate blots thereof, document levels of δ secretase in the lysates obtained from SH-SY5Y cells treated as described in (a). Ponceau S staining was used as a loading control. Data are expressed as relative to WT Aβ- (set to 1) and given as mean ± SEM from n = 9 biological replicates. Two-Way ANOVA with Uncorrected Fisher´s LSD. e Experiment as in (c), quantifying levels of Lgmn transcripts in SY5Y cells treated as described in (a). Data are expressed as relative expression levels (set to 1 for WT-Aβ) and given as mean ± SEM from n = 3 biological replicates per group. This experiment was performed once. f Model of pathological cascade induced by Aβ stress imposed on astrocytes (see discussion section for details). p-values for all statistically significant differences are indicated on the graphs. Source data are provided in the Source Data file.