Figure 5.
NA depletion elevates expression of iNOS and NO-dependent peroxynitrite formation. A, Confocal immunostaining for 3-NT and Aβ1–42 of control (tg-con) and dsp4-treated (tg-dsp4) APP23 mice illustrated an increased plaque-related 3-NT staining, indicating NO-dependent peroxynitrite formation at sites of amyloid deposition. Additional confocal analysis revealed that 3-NT strongly colocalized with the neuronal marker NeuN (white star); additionally, non-3-NT-labeled neurons (white plus sign) and non-NeuN-labeled cells mainly of microglial morphology (white arrow) were observed. Scale bars, 50 μm. B, Hippocampal lysates of wild-type controls (wt-con), wild-type dsp4-mice (wt-dsp4), tg-con, and tg-dsp4 were used for Western blot detection of iNOS. Densitometric analyses showed a strong increase of iNOS protein in dsp4-treated APP23 mice (mean ± SEM; n = 8 animals per group; ANOVA, followed by a Tukey’s test). **p < 0.01 for wt-con versus tg-dsp4; #p < 0.05 for tg-con versus tg-dsp4. C, The number of NeuN/3-NT-colabeled neurons was counted in consecutive rings around the plaque centers, revealing a significant increase in NeuN/3-NT-labeled neurons from 26 to 75 μm in dsp4-treated APP23 mice (mean ± SEM; n = 6; ANOVA, followed by a Tukey’s test). *p < 0.05; **p < 0.01.