Figure 4.

Loss of NA increases neuronal cell loss in APP23 mice. A, Neurons were identified by immunostaining for the neuronal marker NeuN in wild-type controls (wt-con), wild-type mice after noradrenergic depletion with dsp4 (wt-dsp4), APP23 controls (tg-con), and APP23 mice after dsp4 treatment (tg-dsp4). Additional acid fuchsin staining was performed to identify degenerating neurons. The plaque center is marked with a plus symbol (+). Scale bar, 100 μm. B, Quantification of NeuN staining in the frontal cortex (FC), the hippocampal CA1 region (CA1), and the subiculum (Sb) showed a similar number of NeuN-positive neurons in wt-con and wt-dsp4 animals but indicated a small decrease for intact APP23 (tg-con). Areas lacking staining (apparent holes) represent sites of Aβ plaque deposition and were excluded from quantification. Noradrenergic depletion of APP23 (tg-dsp4) increased the loss of neurons in all of the regions that were investigated, but not in the paraventricular thalamus (THL). Quantification of acid fuchsin staining of wt-con, wt-dsp4, tg-con, and tg-dsp4 demonstrated a corresponding increase in degenerating neurons. To assess the relation between amyloid deposition and neuronal cell death, we determined acid fuchsin-labeled cells and their distance from the plaque center (mean ± SEM; n = 20 animals per group; ANOVA, followed by Tukey’s test). *p < 0.05 and **p < 0.01 for tg-con versus wt-con; ^#p < 0.05 for tg-con versus tg-dsp4.