Fig. 6

AAV9 AAV9 Tau ΔD421 induces tau-PSR; SSAT disruption prevents polyamine dysregulation. a–h Representative images and quantification of western blot analysis of hippocampal polyamine dysregulation (ODC, OAZ1, SRM, SMS, SMOX, PMF1, and PMFBP1) in response to 4-month incubation of either AAV9 empty capsid (EC) or AAV9 Tau ΔD421 in 15-month-old nTg and SSAT-/- mice (n = 4–5). ODC: Simple main effects analysis showed that AAV9 Tau ΔD421 significantly decreased ornithine decarboxylase (ODC) (F(1, 16) = 13.164, p = .002). Further, within each genotype, pairwise comparisons revealed a significant reduction of ODC by AAV9 Tau ΔD421 in SSAT-/- mice (p = .003); an effect that was absent in non-transgenic mice. No main effect of genotype (F(1, 16) = 2.358, p = .144) or interaction of factors (F(1, 16) = 1.511, p = .237) was detected on ODC. OAZ1: No main effect of genotype (F(1, 16) = .040, p = .844), AAV9 Tau ΔD421 (F(1, 16) = 3.430, p = .083), or interaction of factors (F(1, 16) = .388, p = .542) was detected in OAZ1. SRM: No main effect of genotype (F(1, 16) = 4.035, p = .062), AAV9 Tau ΔD421 (F(1, 16) = .064, p = .804), or interaction of factors (F(1, 16) = .300, p = .592) was detected in SRM. SMS: Simple main effects analysis showed that AAV9 Tau ΔD421 significantly decreased spermine synthase (SMS) (F(1, 15) = 23.066, p = .000). No effect of genotype (F(1, 15) = 1.918, p = .186) or interaction of factors (F(1, 15) = .850, p = .371) was detected on SMS. SMOX: No main effect of genotype (F(1, 16) = .519, p = .482), AAV9 Tau ΔD421 (F(1, 16) = 2.604, p = .126), or interaction of factors (F(1, 16) = .121, p = .733) was detected in SMOX. PMF1: Simple main effects analysis showed that SSAT disruption significantly increased polyamine-modulated factor 1 (PMF1) (F(1, 16) = 4.522, p = .049). No main effect of AAV9 Tau ΔD421 (F(1, 16) = .114, p = .740) or interaction of factors (F(1, 16) = .000, p = .993) was detected in PMF1. PMFBP1: Simple main effects analysis showed that SSAT disruption significantly increased polyamine-modulated factor binding protein 1 (PMFBP1) (F(1, 16) = 6.499, p = .021). Further, within each genotype, while there was no simple main effect of AAV9 Tau ΔD421 (F (1,16) = 3.248, p = .090), pairwise comparison revealed a significant difference in PMFBP1 between only the SSAT-/- AAV9 empty capsid and SSAT-/- AAV9 Tau ΔD421 groups (p = .017), identifying a SSAT-dependent effect of AAV9 Tau ΔD421 on PMFBP1. There was no significant interaction of factors (F(1, 16) = 3.786, p = .069) on PMFBP1. 2 × 2 Factorial analysis of variance (ANOVA), followed by pairwise comparisons using Fishers PLSD. *p < .05; asterisks indicate the main effect of treatment and main effect of genotype, number signs indicate the pairwise comparison within genotype. Data is represented by means ± S.E.M.