Fig 2: Neuronal repair is induced in the hippocampus of 5XFAD mice ICV-injected with Th1-BDNF cells.5XFAD mice (11–12 months old) were ICV-injected with Th1-GFP cells, Th1-BDNF cells, or PBS (n = 6–7 mice per group). As an additional baseline control experiment, 5XFAD mice and littermate WT controls were injected with PBS (n = 6–7 mice per group). The mice were killed 10 d following the injection and their brains were excised and analyzed with WB. (A) WB analysis of PSD95, synaptophysin (Syn), SNAP25, VAMP25, and NeuN in whole hippocampal homogenates from WT and 5XFAD mice ICV-injected with PBS. Tubulin was used as an internal control. Bar graphs indicate the mean (± SEM) levels of each protein, normalized to tubulin levels in each lysate. (B) WB analysis of the above-mentioned proteins in whole hippocampal homogenates from 5XFAD mice ICV-injected with Th1-GFP cells, Th1-BDNF cells, or PBS. Actin was used as an internal control. Bar graphs indicate the mean (± SEM) levels of PSD95 (p = .2852), synaptophysin (Syn) (p = .124), SNAP25 (p = .0939), VAMP25 and NeuN, normalized to actin levels for each lysate. *p < .05 (one-way ANOVA).

Fig 3: Effect of OMO on APP, tau, SYP, and caspase-3 protein levels in the hippocampus of D-galactose and Aβ25–35-treated AD rats. The Western blot analysis for APP, tau, SYP, and caspase-3 in the rat hippocampus after OMO treatment. The graphs show the levels of (b) APP, (c) tau, (d) SYP, and (e) caspase-3 when compared to the GAPDH levels. These values are expressed as mean ± SD, n = 6. ##P < 0.01, compared with the normal control group; ∗P < 0.05 and ∗∗P < 0.01, compared with the model group.

Fig 4: Cognitive-related protein expression in the hippocampus. (A and B) The protein levels of SYP, PSD-95 and MAP-2 in the hippocampus after NSC transplantation. (C-E) Relative levels of SYP, PSD-95 and MAP-2 protein. *P<0.05 compared with WT group; #P<0.05 compared with Tg-AD group. SYP, synaptophysin; PSD-95, postsynaptic density protein 95; MAP-2, microtubule-associated protein; NSC, neural stem cell; WT, wild-type; Tg, transgenic; AD, Alzheimer's disease.

Fig 5: Inhibition of 14-3-3 proteins leads to reduced numbers of synaptic GluN2A puncta in primary glutamatergic cortical and hippocampal neurons.A, Representative images of YFP-difopein or YFP infected cortical neurons labeled with GluN2A (red), YFP (green), and SYP (blue) at DIV21. Bars, Illustrate numbers of synaptic GluN2A puncta/50 μm in YFP-difopein treated glutamatergic cortical neurons normalized to YFP controls (two-tailed unpaired Student’s t-test: **** p<0.0001, n = 8). B, Representative images of YFP-difopein or YFP infected hippocampal neurons labeled with GluN2A (red), YFP (green), and SYP (blue) at DIV21. Bars, Illustrate numbers of synaptic GluN2A puncta/50 μm in YFP-difopein treated glutamatergic hippocampal neurons normalized to YFP controls (two-tailed unpaired Student’s t-test: ** p = 0.0020, n = 9). Error bars indicate SD. Scale bar, 10μm.