Additional file 1: of Concomitant histone deacetylase and phosphodiesterase 5 inhibition synergistically prevents the disruption in synaptic plasticity and it reverses cognitive impairment in a mouse model of Alzheimer’s disease

Additional methods. Table S1. Pharmacokinetic parameters and blood-brain barrier permeability for vorinostat and tadalafil. Figure S1. Mean plasmatic concentration evolution versus time after different administrations of vorinostat (SAHA, 12.5 mg/kg, i.p. administration) (a), tadalafil (1 mg/kg, oral administration) (b) and concomitant vorinostat and tadalafil administration (12.5 mg/kg, i.p. administration, and 1 mg/kg, oral administration, respectively) (c). Figure S2. Memory tests after chronic treatment with vehicle in non-transgenic mice (WT) compared to transgenic mice (Tg2576). Figure S3. (a) Representative Western blot bands using the AT8 (pTau) antibody normalized to total tau (T46) in cortical tissues of WT and Tg2576 animals treated with vehicle. The histograms represent the quantification of the immunochemically reactive bands in the Western blot. An increase in pTau levels in Tg2576 mice receiving vehicle are shown compared to WT-vehicle mice. Results are expressed as mean ± SEM (n = 8–10 in each group) (**p ≤ 0.01). (b) Representative Golgi staining images of the apical dendrites on CA1 hippocampal pyramidal neurons in WT and Tg2576 animals treated with vehicle. Scale bar: 10 μm. WT vehicle group showed a significantly higher level in the spine density of apical dendrites on hippocampal CA1 pyramidal neurons than Tg2576 vehicle mice (n = 34–36 neurons; ***p ≤ 0.001). (PDF 270 kb)