Figure 6. Aβ-dependent alterations in the dentate gyrus are associated with increased susceptibility of hAPP_FAD mice to seizures induced by a GABA_A antagonist.

Mice were injected IP with PTZ (40 or 80 mg/kg). Brain tissues were collected 20 min thereafter, or earlier if they developed fatal seizures. Behavior was video-recorded, and seizure severity was scored off-line. (A) Compared with NTG controls, hAPP-J20 mice had shorter latencies to reach a given seizure severity (left), greater overall seizure severity (center), and more seizure-associated deaths (right). (B) hAPP-ARC48 mice and hAPP-J9/FYN mice also had increased overall seizures severity compared with littermate controls. (C) hAPP-J9/FYN mice also had a greater incidence of seizure-associated death than the control groups. (D) All NTG mice treated with 80 mg/kg of PTZ developed fatal seizure activity. (E-G) Protein levels of NPY (E), calbindin (F), and Fos (G) in the dentate gyrus were not altered by fatal seizures. (H-K) Compared with hAPP-J20 mice that survived the PTZ injection, hAPP-J20 mice that developed fatal seizures had higher levels of NPY in the dentate gyrus and mossy fibers (H), lower dentate calbindin levels (I), and lower numbers of granule cells expressing Fos (J) or Arc (K). *P<0.05, **P<0.01, ***P<0.001 vs. NTG by Student’s t test or Tukey-Kramer test. ^#P<0.05, ^##P<0.01 by Fisher’s exact test.