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. 2009 Nov 9;119(12):3692–3702. doi: 10.1172/JCI39716

Figure 4. Prevention trial of NSAIDs inhibits neuronal CCEs.

Figure 4

(A–C) R1.40 transgenic mice placed on a control diet for 3 months beginning at 3 months of age exhibited expression of cyclin A (A) in numerous NeuN-positive (B) neurons on the frontal cortex layers II/III, similar to previously published results (30). Large arrows indicate cyclin A–positive neurons. (D–I) R1.40 animals placed on the 3-month ibuprofen- (D–F) or naproxen-containing (G–I) diet exhibited expression of cyclin A (D and G) in a subset of NeuN-positive (E and H) neurons. Similar results were obtained with immunohistochemistry for the cell cycle protein cyclin D (not shown). (C, F and I) Merged images. Nuclei were counterstained with DAPI (blue). FISH with a DNA probe to mouse chromosome 13 demonstrated a subset of neurons with 3 or 4 spots of hybridization in R1.40 animals fed the control diet (C, inset), while the ibuprofen and naproxen treatment groups exhibited only 2 spots of hybridization (F and I, insets). Small arrows indicate FISH signals in the neuronal nucleus. Scale bars: 100 μm (A–I); 10 μm (insets).