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. Author manuscript; available in PMC: 2022 May 9.
Published in final edited form as: Sci Signal. 2021 Nov 9;14(708):eabg2648. doi: 10.1126/scisignal.abg2648

Fig. 4. Inability to phosphorylate Ser940 or Thr1007 in knock-in pups regulated neonatal seizure susceptibility.

Fig. 4.

(A) Graphical representation of homozygous S940A knock-in mutant mice (26) and homozygous T1007A knock-in mutant mice (25). (B and C) S940A+/+ mice had spontaneous epileptiform discharges (SEDs) at P7 and P12. (D) Spontaneous epileptiform discharge duration of P7 S940A+/+ pups administered CLP290 10’ treatment. Naïve P7 S940A+/+ n=6, naïve P12 S940A+/+ n=4, and CLP290 10’ P7 S940A+/+ n=6 pups. (E to G) P7 T1007A+/+ pups are resistant to ischemic neonatal seizures. (E) EEG traces and (F) seizure frequency raster plots for P7 WT, S940A+/+, and T1007A+/+pups that underwent unilateral carotid ligation. (G) 1st-hour vs 2nd-hour seizure burdens after unilateral carotid ligation, plotted as percent WT. WT n=12, S940A+/+ n=12, and T1007A+/+ n=9 pups. (H) P7 S940A+/+ ischemic seizures in response to CLP290 (10’). Seizure burden of CLP290 10’ treated P7 S940A+/+ pups after unilateral carotid ligation plotted as P7 percent naïve S940A+/+. CLP290 10’ treated P7 S940A+/+ n=11 pups. (I) Seizure burden of P10 S940A+/+ pups (n=8) after unilateral carotid ligation, plotted as P7 percent naïve S940A+/+. n.s., P=0.57. (J to O) Naïve P12 S940A+/+ mice are susceptible to status epilepticus and mortality. (J) Representative EEG trace and (K) seizure frequency raster plot of naïve P12 WT, S940A+/+, and T1007A+/+ pups. Black bars indicate intraperitoneal pentylenetetrazol (PTZ) injections. (L) Total seizure burden of P12 S940A+/+ pups after PTZ administration plotted as percent WT. (M) 1st-, 2nd-, and 3rd-hour seizure burdens at P12 in T1007A+/+ pups plotted as percent WT. (N) 1st-hour average seizure durations for S940A+/+ and T1007A+/+ P12 pups, plotted as percent WT. (O) Survival plot for P12 WT, T1007A+/+, and S940A+/+ pups during the PTZ challenge. P12 WT n=11; S940A+/+ n=11; and T1007A+/+ n=6 pups. (P) Duration of time to righting reflex at P7 and P12 in naïve WT, T1007A+/+, and S940A+/+ pups. (n=8 pups each group). *P<0.05; **P<0.01; ***P<0.001 by unpaired t-test vs. WT for all seizure data. Survival analysis ***P<0.001 by Mantel-Cox test. Righting Reflex by one-way ANOVA.