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Fig. 7 | Acta Neuropathologica Communications

Fig. 7

From: High-throughput microscopy exposes a pharmacological window in which dual leucine zipper kinase inhibition preserves neuronal network connectivity

Fig. 7

DLK inhibition has both neuro-protective and -restorative potential in cultures overexpressing hTau.P301L. a Cultures overexpressing hTau.P301L, showed impaired neuronal network connectivity (Morph.: nbio = 2 x ntech = 6 - Func.: nbio = 2 x ntech = 9); b Continuous treatment with DLK inhibitors prevented loss of neuronal connectivity of the hTau.P301L model according to the normalized connectivity scores (Morph.: nbio = 2 x ntech = 6 - Func.: nbio = 2 x ntech = 9); c Representative images of control cultures, cultures overexpressing hTau.P301L and hTau.P301L cultures treated with 1 μM GNE8505 (I, II and III in panel b); d Bar graphs showing z-scores of morphological descriptors (nbio = 2 x ntech = 6) as well as the absolute number of correlated calcium bursts (nbio = 2 x ntech = 9). Significant differences compared to control cultures or cultures overexpressing hTau.P301L are indicated (p < 0.05, pairwise Wilcoxon test with Bonferroni correction); e DLK inhibition rescues cultures overexpressing hTau.P301L after connectivity loss had already started (Morph.: nbio = 1 x ntech = 6 - Func.: nbio = 1 x ntech = 6); f Representative images of control cultures, cultures overexpressing hTau.P301L and hTau.P301L cultures treated with 1 μM GN3511 or 10 μM GNE8505 (IV, V, VI and VII in panel e); g Bar graphs showing z-scores of morphological descriptors (nbio = 1 x ntech = 6) as well as the absolute number of correlated calcium bursts (nbio = 1 x ntech = 6). Significant differences compared to control cultures or cultures overexpressing hTau.P301L are indicated (p < 0.05, pairwise Wilcoxon test with Bonferroni correction)

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