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. 2007 Jun 21;26(13):3169–3179. doi: 10.1038/sj.emboj.7601758

Figure 4.

Figure 4

Resveratrol prevents neurodegeneration in p25 transgenic mice. (A) Experimental design for ICV injection of resveratrol (Resv) or vehicle (Veh) in p25 transgenic mice (n=5 for vehicle (Veh); n=9 for resveratrol (Resv)). (B) Acetylation levels of PGC-1alpha is decreased in p25 animals treated with resveratrol, compared to p25 animals injected with vehicle. Shown also is densitometry-based analysis of acetylated PCG-1alpha levels. (C) Downregulation of activated caspase 3 and GFAP, markers of cell death and astrogliosis, in the hippocampus of p25 transgenic mice treated with resveratrol (n=3), compared to p25 animals injected with vehicle (n=2), as revealed by Western blots. Uninjected age-matched WT mice (n=2) were also compared as a control. SIRT1 levels are increased in p25 transgenic mice compared to WT mice, but are similar between resveratrol and vehicle-treated mice. Densitometry values for activated caspase 3, GFAP and SIRT1 are also shown. Actin and FAK are used for loading controls. (D) Reduction of GFAP-expressing cells in CA1 of p25 transgenic mice treated with resveratrol (n=3), compared to p25 animals injected with vehicle (n=2) and uninjected WT controls (n=2) as revealed by immunofluorescence staining. Scale bar, 15 μm. (E) Immunofluorescence staining revealed reduced caspase 3 activation and higher number of p25-GFP expressing cells in CA1 of p25 transgenic mice (n=2) injected with resveratrol versus vehicle (n=2). Scale bar, 50 μm. (F) Two weeks induced p25 transgenic mice were injected ICV with either resveratrol (n=9) or vehicle (n=5) 2–3 × /week for 3 weeks. An additional control group of p25 transgenic mice was not injected with vehicle or resveratrol (n=8). Subsequently all groups and WT mice (n=20) were subjected to contextual fear conditioning. Left: resveratrol had no effect on the total activity and escape response to the electric foot shock during the training procedure. ES, electric foot shock. Right: vehicle treated and non-treated p25 transgenic mice displayed reduced freezing behavior during the memory test when compared to WT littermates (P=0.0032, t(1,23)= 3.295; P<0.0001, t(1,26)= 5.048). However, when compared to the vehicle group (P= 0.0109, t(1,12)=3.009) or non-treated p25 transgenic mice (P= 0.0005 t(1,15)=4.407) resveratrol-treated p25 transgenic mice showed significantly improved freezing behavior during the memory test. * Denotes significant difference; ES, electric foot shock.