Conditional deletion of endothelial Cdk5 induces spontaneous seizures. (A) Spontaneous seizure rates and frequencies in Cdh5-Cre;Cdk5f/f and Cdk5f/f mice at different ages. (B–D) Typical EEGs recorded from the cortex (CTX) and hippocampus (HP) in Cdk5f/f and Cdh5-Cre;Cdk5f/f mice (B) or Cdh5-CreERT2;Cdk5f/f mice (C) and Cdk5f/f mice injected with BR1-Con or BR1-iCre (D). (E) PTZ-induced seizure onset latency and duration in Cdh5-Cre;Cdk5f/f and Cdk5f/f mice at 4 wk (n = 5 mice per group; *, P < 0.05; unpaired two-tailed Student’s t test). (F) Hippocampal glutamate concentrations in Cdh5-Cre;Cdk5f/f and Cdk5f/f mice at 4 wk (left) and 16 wk (right; n = 4–5 mice per group; **, P < 0. 01; ***, P < 0.001; unpaired two-tailed Student’s t test). (G) Example traces of AP responses to positive current injection treatment at 150 pA with or without AP5 (20 mM) and CNQX (40 mM) in 4-wk-old Cdh5-Cre;Cdk5f/f and Cdk5f/f mice. (H) Quantification across 0–300-pA current injections in 10-pA steps (n = 5 mice per group; ***, P < 0.001; two-way ANOVA followed by Tukey’s multiple comparisons test). (I) Representative traces and AP firing frequencies induced by 500-ms treatment with 100 µM glutamate in Cdh5-Cre;Cdk5f/f and Cdk5f/f mice (n = 5 mice per group; ***, P < 0.001; unpaired two-tailed Student’s t test). (J) Traces showing sEPSC and mEPSC recorded in Cdh5-Cre;Cdk5f/f and Cdk5f/f mice. (K–N) Cumulative probability plots summarizing the mean sEPSC amplitudes (K) and sEPSC inter-event intervals (L) and cumulative probability plots summarizing the mean mEPSC amplitudes (M) and mEPSC inter-event intervals (N) in Cdh5-Cre;Cdk5f/f and Cdk5f/f mice at 4 wk. The insets depict the average sEPSC and mEPSC amplitudes and frequencies (n = 5 mice per group; **, P < 0.01; ***, P < 0.001; unpaired two-tailed Student’s t test). The numbers inside the bars represent the numbers of cells from five mice. The data are presented as means ± SEM. n.s., not significant.
