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Image Search Results
Journal: Acta Neuropathologica
Article Title: Hyperphosphorylated tau causes reduced hippocampal CA1 excitability by relocating the axon initial segment
doi: 10.1007/s00401-017-1674-1
Figure Lengend Snippet: Pseudo-phosphorylated tau relocates the AIS down the axon in a process mediated by microtubules. Representative photomicrograph of A14- ( top ) and E14-tau-EGFP ( lower ) transfected hippocampal neurons stained for ankyrin G a 24 h and b 48 h after transfection. Arrows indicate the start, middle and end of the AIS as determined by quantitative analysis of the c , d axonal fluorescence profile. The dashed line indicates the normalized detection threshold. Quantification of ankyrin G labeling in neurons transfected with E14- ( blue ) and A14-tau ( black ) for e 24 h (start p = 0.48, middle p = 0.94, end p = 0.54; E14 n = 61, A14 n = 46) and f 48 h (start p = 0.0001, middle p = 0.0027, end p = 0.0017; E14 n = 47, A14 n = 62). AIS location of E14- and A14-tau-transfected neurons labeled for g βIV spectrin (start p = 0.0041, middle p = 0.0024, end p = 0.0084; E14 n = 55, A14 n = 52) and h Na V 1.6 (start p = 0.0042, middle p = 0.0045, end p = 0.0316; E14 n = 53, A14 n = 53). Using ankyrin G staining, the role of site-specific phosphorylation in AIS relocation was determined: i AT180 ( start p = 0.0138, middle p = 0.44, end p = 0.76; AT180E n = 53, AT180A n = 52), j 12E8 (start p = 0.0183, middle p = 0.0352, end p = 0.09; 12E8E n = 54, 12E8A n = 51), and k PFH1 (start p = 0.34, middle p = 0.56, end p = 0.75; PHF1E n = 50, PHF1A n = 38). l Treatment with 0.1 µM taxol ( magenta ) prevents AIS relocation (start, ANOVA, F = 8.05, p = 0.0005; middle, ANOVA, F = 4.057, p = 0.0191; end, ANOVA, F = 6.614, p = 0.0017; E14 n = 57, A14 n = 54, E14+ taxol n = 51). m Microtubule destabilization with 0.05 µM nocodazole ( green ) relocates the AIS ( gray , control, start: p = 0.0169, middle: p = 0.0297, end: p = 0.0856; nocodazole n = 54, control n = 55). * p < 0.05, ** p < 0.01, *** p < 0.001 and **** p ≤ 0.0001. Data presented as mean ± SEM. Scale bar 5 µm. Statistical comparisons were made using an unpaired two-tailed Student’s t test or a one-way ANOVA with a Sidak’s post hoc test
Article Snippet: Two mutant Tau-EGFP constructs termed E14 and A14 (all 14 serine or threonine residues T111, T153, T175, T181, S199, S202, T205, T212, T217, T231, S235, S396, S404, and S422 mutated to glutamic acid (E14) or alanine (A14), respectively) were generated by subcloning the mutant Tau fragment from
Techniques: Transfection, Staining, Fluorescence, Labeling, Phospho-proteomics, Control, Two Tailed Test
Journal: Acta Neuropathologica
Article Title: Hyperphosphorylated tau causes reduced hippocampal CA1 excitability by relocating the axon initial segment
doi: 10.1007/s00401-017-1674-1
Figure Lengend Snippet: Pseudo-phosphorylated tau reduces AP firing in a similar manner to that observed in tau transgenic mouse models. Representative traces of APs fired by a A14- ( black ), b E14-transfected ( blue ) neurons and c E14-transfected neurons treated with 0.1 µM taxol ( magenta ) following injection of a −60, 0, rheobase and 320 pA current step. d Representative traces of the initial AP fired for A14, E14 and E14+ taxol neurons. Pooled data demonstrating the AP firing, including e input–output relationships (ANOVA, F = 4.084, p = 0.0274; E14 n = 12, A14 n = 11, E14+ taxol n = 10), f AP threshold (ANOVA, F = 2.439, p = 0.10), g AP amplitude (ANOVA, F = 4.152, p = 0.0256), and h rheobase (ANOVA, F = 2.4, p = 0.11). * p < 0.05. Data are presented as mean ± SEM and individual data points. Statistical comparisons were made using a one-way ANOVA with a Sidak’s post hoc test between all three groups
Article Snippet: Two mutant Tau-EGFP constructs termed E14 and A14 (all 14 serine or threonine residues T111, T153, T175, T181, S199, S202, T205, T212, T217, T231, S235, S396, S404, and S422 mutated to glutamic acid (E14) or alanine (A14), respectively) were generated by subcloning the mutant Tau fragment from
Techniques: Transgenic Assay, Transfection, Injection