Fig. 3: Expression of neurotrophic factors and neural activity in co-culture model.

a Neurotrophic factor BDNF, GDNF and MANF and (b) neurotransmitter receptor GRIN2D, GRIK2 and GABRA2 gene expression. c Timeline for co-culture design and MEA recording. d Representative images from CTRL iMGL co-cultures at 30 and 60 days in vitro (DIV) with stainings for NGN2-neurons (MAP2, red), rat astrocytes (GLT1, magenta), iMGLs (ABI3, green), and nuclei (DAPI). e Representative raster plots from weekly CTRL iMGL co-culture MEA recordings. Spikes detected on individual electrodes marked with black lines, bursts with blue lines and network bursts with purple boxes. f MEA recording results as Number of spikes (95% CI of diff. = −27,769 to −3067, adj.p = 0.0212; 95% CI of diff. = −11,671 to −1434, adj.p = 0.0104; 95% CI of diff. = −8259 to −331.2, adj.p = 0.0366; 95% CI of diff. = −19,980 to −4147, adj.p = 0.0113), Weighted mean firing rate (95% CI of diff. = −2.821 to −0.4223, adj.p = 0.0152; 95% CI of diff. = −1.418 to −0.07197, adj.p = 0.0288; 95% CI of diff. = −2.117 to −0.3807, adj.p = 0.0139), Network IBI coefficient of variation (95% CI of diff. = −1.499 to −0.1199, adj.p = 0.0222; 95% CI of diff. = −1.181 to −0.4205, adj.p = 0.0060), and Synchrony index (95% CI of diff. = −0.6299 to −0.09522, adj.p = 0.0125; 95% CI of diff. = −0.6945 to −0.09386, adj.p = 0.0147) from co-culture with and without iMGLs. n = 5–7 wells for no iMGL and n = 6–10 wells from two CTRL iMGL lines. g MEA recording results as Number of spikes, Weighted mean firing rate, ISI coefficient of variation, Number of bursts, Burst duration (95% CI of diff. = −0.1197 to −0.007484, adj.p = 0.0368; 95% CI of diff. = −0.2053 to −0.05687, adj.p = 0.0165), Mean ISI within burst (95% CI of diff. = 0.0004615 to 0.01288, adj.p = 0.0436; 95% CI of diff. = 0.002695 to 0.01507, adj.p = 0.0248; 95% CI of diff. = 0.005213 to 0.007635, adj.p = 0.0019), Network IBI coefficient of variation (95% CI of diff. = −1.574 to −0.3703, adj.p = 0.0197; 95% CI of diff. = −1.173 to −0.1141, adj.p = 0.0331), and Synchrony index (95% CI of diff. = −0.3168 to −0.1937, adj.p = 0.0030; 95% CI of diff. = −0.6867 to −0.03380, adj.p = 0.0414) from ST, HT and CTRL iMGL co-cultures. n = 3 lines per group. Dunnett’s (timepoints compared to week 4 timepoint) or Tukey’s (comparison between with/without iMGL groups) multiple comparisons tests were used for significance. CTRL healthy individuals, ST affected twin, HT healthy twin.