Fig. 1

14-3-3θ overexpression reduces and 14-3-3 inhibition increases social dominance deficits induced by fibrillar αsyn. a Transgenic difopein-eYFP expressing or 14-3-3θ-overexpressing transgenic mice and matching WT littermates were given a unilateral stereotactic injection of mouse αsyn monomer or PFFs in the striatum (STR) at 8–12 weeks of age. At 3 or 6 months post injection (mpi), mice underwent behavioral testing. Mice were then perfused, and their brains were sectioned by microtome and processed for immunohistochemical staining. b WT mice were given a unilateral injection of AAV-14-3-3θ/GFP or AAV-GFP in the substantia nigra (SN) at 8 weeks of age. 4 weeks after AAV inoculation, mice were given an ipsilateral stereotactic injection of αsyn monomer or PFFs in the STR at 12 weeks of age. Mice underwent behavioral testing at 6 mpi. Mice were then perfused, and their brains were sectioned by microtome and processed for immunohistochemical staining. c 14-3-3θ overexpression increased average win rate in comparison to WT PFF-injected mice. Quantification of win rate of 14-3-3θ mice injected with monomer, 14-3-3θ mice injected with PFFs, or WT mice injected with PFFs in the tube test matched against monomer-injected WT mice at 6 mpi. Each mouse was matched against 3 separate WT mice injected with monomer over 3 individual rounds, and the win rate per mouse was determined across these 3 trials. n = 17–25 mice per group. *p < 0.05 (Tukey’s multiple comparison test). Error bars represent SEM. d Difopein transgenic expression in the cortex and amygdala decreased average win rate in comparison to PFF-injected WT mice. Quantification of difopein mice injected with monomer, difopein mice injected with PFFs, and WT mice injected with PFFs at 3 mpi in the tube test matched against monomer-injected WT mice. Mice were evaluated over 3 individual rounds. n = 14–16 per group. *p < 0.05 (Tukey’s multiple comparison test). Error bars represent SEM. e Quantification of difopein mice injected with monomer, difopein mice injected with PFFs, and WT mice injected with PFFs at 6 mpi in the tube test matched against monomer-injected WT mice. Mice were evaluated over 3 individual rounds. n = 14–15 per group. *p < 0.05, **p < 0.01 (Tukey’s multiple comparison test). Error bars represent SEM