Figure 6

The p38 inhibitor SB203580 enhances hippocampal spike activity in APP23 mice. (A) Immunoblot using hippocampal lysates from APP23 transgenic or non-transgenic (non-tg) mice injected with riluzole (RIL), MK801 (MK) or vehicle control (VEH) probed for human APP, phospho-p38, p38 and GAPDH. Representative blot with 3 mice per group is shown. (B) Quantification of immunoblots (n = 3-4) means ± s.d. **p < 0.01 (ANOVA) (C) Immunoblot of hippocampal lysates from APP23 transgenic mice or non-transgenic (non-tg) injected with SB203580 (SB, 0.4 mg/kg i.p.) or vehicle control (VEH) probed for human APP, phospho-p38, p38 and GAPDH. Representative blot with 3 mice per group is shown. (D, E) Representative EEG trace (LFP) and periodogram (0-60 Hz) of (D) non-transgenic and (E) APP23 transgenic mice before and after injection of SB203580 (0.4 mg/kg i.p.). (F) Magnified EEG traces marked in D and E by dashed box. (n = 5). (G) Spike train quantification. (n = 5) Means ± s.e.m.; ND, none detected (H) Spectral power analysis of APP23 and non-transgenic (non-tg) recordings before and 60 minutes after injection of SB203580. Dashed box marks theta band. Means ± s.e.m. (n = 5). (I) Quantification of spectra in H. AUC, area under curve. Means ± s.e.m. **p < 0.01 ns, not significant (ANOVA) (J) Spectral power of EEG waves in APP23 transgenic mice and non-transgenic (non-tg) controls before and 60 minutes after injection of SB203580. Dashed box marks gamma band. Means ± s.e.m. (n = 5). (K) Quantification of spectra in J. AUC, area under curve. Means ± s.e.m. ***p < 0.005 **p < 0.01 *p < 0.05 (ANOVA) (L) Modulation index before and 60 minutes after injection of SB203580. (n = 5) means ± s.e.m. **p < 0.01 *p < 0.05 ns, not significant (ANOVA).