Fig. 5 | Nature Communications

Fig. 5

From: Modulation of AMPA receptor surface diffusion restores hippocampal plasticity and memory in Huntington’s disease models

Fig. 5

Tianeptine’s effect on BDNF intracellular transport and AMPAR surface diffusion is mediated by BDNF-TrkB signaling pathway. a Representative kymographs of intracellular transport of BDNF-containing vesicles (white trajectories) in a neurite (50 μm from soma) over 75 s in polyQ-HTT-expressing rat hippocampal neurons treated with vehicle, tianeptine (50 μM), or Cyclotraxin-B (CB) (1 μM) plus tianeptine (50 μM). b, c Anterograde and retrograde BDNF transport velocity in all neurites of polyQ-HTT-expressing rat hippocampal neurons treated with vehicle, tianeptine (50 μM), or CB (1 μM) plus tianeptine (50 μM) (b) or treated with vehicle, BDNF (100 ng ml1), tianeptine (10 μM), or BDNF (100 ng ml−1) plus tianeptine (10 μM) (c); values are median ± 95% c.i. (b, c); n = 4322, 4017, 4199, 4354, 3887, and 3954 trajectories for anterograde and retrograde velocity in polyQ-HTT-expressing neurons treated with vehicle, tianeptine, and CB plus tianeptine, respectively (b); n = 3505, 3382, 3339, 2099, 3346, 3174, 3190, and 2022 trajectories for anterograde and retrograde velocity in polyQ-HTT-expressing neurons treated with vehicle, BDNF, tianeptine, and BDNF plus tianeptine, respectively (c). d Typical GluA2-QD trajectories (magenta) in polyQ-HTT-expressing rat hippocampal neurons, treated with vehicle, tianeptine (50 μM), CB (1 μM) plus tianeptine (50 μM), or TrkB-Fc (1 μg ml−1) plus tianeptine (50 μM). Scale bar, 10 μm. e GluA2-AMPAR diffusion coefficients in FL-polyQ-HTT-expressing rat hippocampal neurons treated with vehicle, tianeptine (50 μM), CB (1 μM), plus tianeptine (50 μM), or TrkB-Fc (1 μg ml−1) plus tianeptine (50 μM); data are shown as median ± 25–75% IQR; n = 601, 535, 708, and 556 trajectories for 4 groups, respectively. Data are representative of a minimum of three independent experiments. Significance was assessed by Kruskal–Wallis test followed by Dunn’s multiple comparison test (b, c, e); ***P< 0.001; ns not significant

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