Figure 4.

Repeated rapamycin treatment maintains suppression of epileptiform activity. NS-Pten knockouts received a single course of rapamycin during postnatal weeks 4–5 and a subset received additional courses of treatment during weeks 10–11 and 16–17 (Rapa x3, red). A) Knockouts that only received the initial treatment (Rapa x1, blue) showed a significant increase in epileptiform activity at 13 weeks (n=6 for weeks 4–10, n=3–4 for weeks 11–13, and n=1 for weeks 14–18; low sample size is due to premature death; see Figure 5), as compared to the Rapa x3 group (n=5–8 for weeks 4–13, and n=4–6 for weeks 14–18). For comparison, previous data from naïve and vehicle-treated knockouts (Ljungberg et al., 2009) are also plotted, but eliminated from statistical analyses (Control, n=12–14, black). Note that statistical analyses between the rapamycin-treated groups could not be made after 13 weeks due to premature deaths in the Rapa x1group resulting in a sample size <3 (represented by a dotted line), however all available data are plotted. B) Rapa x3 knockouts demonstrated continued suppression of epileptiform activity as compared to the Rapa x1 group at 13 weeks. Data are presented as the median for each age and treatment group. Analysis was performed using the Mann-Whitney U test due to unequal variances. For weeks 4–13, comparisons were made between treatment groups (A); for weeks 14–18, comparisons were made against the Rapa x1 group at 13 weeks (B). *p<0.05.