Figure 4

Cellular effects exerted by ibuprofen in a murine model of Alzheimer disease (AD) overexpressing GSK-3β. To study whether ibuprofen treatment reverses the cellular alterations shown by this murine model of AD, the morphology and connectivity of retrovirus-labeled granule neurons were examined after an 8-week treatment. (a–d) Representative images showing retrovirus-labeled neurons of different ages belonging to the distinct experimental groups and genotypes. (e) Quantification of primary apical dendrite length. (f) Quantification of total dendritic length. (g) Percentage of newborn neurons with more than one primary apical dendrite. Ibuprofen significantly increased total dendritic (f) and primary apical dendrite length (e) and reduced the percentage of cells with more than one primary apical dendrite (g) in GSK-3β-overexpressing (GSK-3-OE) mice. (h) Cell migration into the granule cell layer. GSK-3-OE mice also showed increased cell migration into this layer. This effect was not reversed after ibuprofen treatment. (i) Sholl’s analysis. The altered morphology observed in the granule neurons of GSK-3-OE mice¹⁷ was completely normalized after ibuprofen treatment. (j–m) Representative images showing retrovirus-labeled neurons belonging to the different genotypes and treatments. (n) Quantification of postsynaptic cluster density. GSK-3-OE mice showed a reduced number of PSD95-GFP⁺ clusters, as previously described.¹⁷ Ibuprofen produced an enormous reduction of PSD95-GFP⁺ clusters in these mice, whereas it produced no change in WT counterparts. (o) Quantification of postsynaptic cluster area. Ibuprofen drastically increased the PSD95-GFP⁺ cluster area in GSK-3-OE mice. (p–s) Representative images showing mossy fiber terminals of retrovirus-labeled neurons belonging to the different genotypes and treatments. (t) Quantification of the mossy fiber terminal area in the CA3 region. GSK-3-OE mice showed a reduced terminal button area, which was further depleted after ibuprofen treatment. MFT, mossy fiber terminal; WT, wild type.