Figure 4. Pharmacological induction of neuronal overexcitation in NTG mice triggers molecular and anatomical alterations resembling those observed in untreated hAPP_FAD mice.

(A-E) NTG mice were injected IP with saline or kainate (KA) (5, 10, 20, or 25 mg/kg) and analyzed 3 days later. (A) Representative photomicrographs depicting KA-induced sprouting of NPY-positive terminals in the molecular layer of the dentate gyrus (arrow) and ectopic expression of NPY in the mossy fibers (arrowhead). (B) Quantitation of KA-induced increases in NPY expression demonstrating dose-dependence. (C) Typical KA-induced reduction of Arc expression in granule cells of the dentate gyrus. (D) This effect was also dose-dependent. (E) Representative western blots of dentate lysates and quantitations of signals, illustrating KA-induced changes in the levels of STEP (left), α7 nAchR (center), and calbindin (right). Each lane represents an individual mouse. (F-H) NTG mice were injected IP with pilocarpine (Pilo) (250 mg/kg) or kainate (25 mg/kg) and euthanized 2 h or 3 days later for analysis of NPY and Arc expression. (F) At these concentrations, both drugs elicited similar overall seizure severity within 20 min after their injections. (G) By 3 days after the injection, KA, but not pilocarpine, increased NPY expression in mossy fibers. (H) By 2 h after the injection, both drugs elicited comparable increases in Arc expression in the neocortex, but only KA elicited marked Arc expression in granule cells. ^#P<0.05, ^##P<0.01, ^##P<0.01 by ANOVA and contrasts test. *P<0.05, **P<0.01, ***P<0.001 vs. Sal by Student’s t test or Tukey-Kramer test.