Figure 4: FCDs and seizures are prevented by chronic postnatal rapamycin treatments but return following rapamycin withdrawal. | Nature Communications

Figure 4: FCDs and seizures are prevented by chronic postnatal rapamycin treatments but return following rapamycin withdrawal.

From: Convulsive seizures from experimental focal cortical dysplasia occur independently of cell misplacement

Figure 4

(a) Diagram illustrating the experimental protocol, including rapamycin treatment at 1 mg kg−1 every 48 h. (b–d) B&W images of RhebCA-electroporated neurons expressing tdTomato in coronal sections from mice treated with either vehicle (b) or rapamycin (c), or following rapamycin withdrawal (d). Scale bar: 100 μm. (e) Bar graphs of the percentage of tdTomato+ RhebCA neurons in layer 2/3 in mice treated with vehicle (N=7) or rapamycin (N=6), or following rapamycin withdrawal (N=5). P<0.0007, one-way analysis of variance (ANOVA) followed by Tukey post hoc, *P<0.05; ***P<0.001, ****P<0.0001. (f,g) Bar graphs of tdTomato+ RhebCA neuron soma size (f) and pS6 immunoreactivity per cell (g) in mice treated with vehicle (N=7) or rapamycin (Rapa, N=6), or following rapamycin withdrawal (N=5). P<0.0001 and P<0.0026, respectively, one-way ANOVA followed by Tukey post hoc. (h–j) Images of RhebCA-electroporated neurons expressing tdTomato and co-stained for pS6 (green and B&W for pS6 only) in coronal sections from mice treated with either vehicle (h) or rapamycin (i), or following rapamycin withdrawal (j). Scale bar, 100 μm. (k–m) Representative examples of EEG recordings in mice containing RhebCA-electroporated cells treated with either vehicle (k) or rapamycin (l), or following rapamycin withdrawal (m). Scale bars, 14 s, 500 μV. (n) Bar graphs of the percentage of RhebCA-electroporated mice displaying seizure activity that were treated with vehicle (black) or rapamycin (red), or following rapamycin withdrawal (green). (o) Plot of the body mass as a function of postnatal days of the animals treated with vehicle (N=7) or rapamycin (N=6). Mean (solid black line)±s.e.m. (colour shaded areas). P<0.0001 (two-way ANOVA with Sidak's multiple comparisons post-test). Significance starts at P13 of age. (p,q) Images of littermates at P5 (p) and 2 months (q) of age treated with vehicle or rapamycin. Error bars, s.e.m.

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