Fig. 5: PTEN inhibitor VO-Ohpic prevents depression-like behaviors and neuron atrophy in Dex-treated mice.

a Diagram of experiment design and timeline for (b–e). b A significant reduction in body weight was observed after 21-day Dex treatment, but it could be partially reversed by intraperitoneal injection of VO-Ohpic into the mice starting on day 11. Data were analyzed using two-way repeated measures ANOVA, *p < 0. 05, **p < 0.01 (Saline versus Dex-treated mice); ^#p < 0.05, ^##p < 0.01 (Dex-treated mice versus Dex-treated mice with VO-Ohpic). c–e Dex resulted in decreased sucrose preference (c), and increased immobility time in TST (d) and FST (e). n = 8 in each group and data were analyzed using one-way ANOVA, **p < 0.01. f, g The levels of CORT in the serum and CRH transcription in the PFC were increased in Dex-treated mice. Data were analyzed using Student’s t-tests, **p < 0.01. h Diagram of experiment design and timeline for (i–m). i–m Three-week Dex treatment led to increased levels of PTEN, p-MEK1, and p-ERK1/2 and reduced level of p-AKT, and these changes were reversed by VO-Ohpic starting on day 11. Note that the levels of ERK1/2, AKT, and MEK1 were not changed by the Dex treatment or application of PTEN inhibitor. n = 4 in each group and data are presented as mean ± SEM. One-way ANOVA (j), *p < 0.05, **p < 0.01. Two-way ANOVA with post hoc Tukey’s test (k–m), *p < 0.05, **p < 0.01. n Diagram of experiment design and timeline for (o–q). o–q Representative images of pyramidal neuron in layers II/III of PFC neurons of control mice and Dex-treated mice with or without VO-Ohpic administration, respectively. Scale bar = 40 μm. r–t Statistical data showing the soma size (r), total length of dendrites (s), and dendritic branching (t) of the PFC neurons in indicated groups. n = 20 cells from 5 mice in each group, and all data are presented as mean ± SEM. One-way ANOVA (r, s), **p < 0.01. Two-way ANOVA with post hoc Tukey’s test (t), *p < 0. 05, **p < 0.01 (control mice versus Dex-treated mice); ^#p < 0.05, ^##p < 0.01 (Dex-treated mice versus Dex-treated mice with VO-Ohpic). u Model of PTEN signaling pathway in CRS-induced neuronal atrophy and depression-like behaviors. CORT, corticosterone; CRH, corticotropin-releasing hormone; CRS, chronic restraint stress; Dex, dexamethasone; FST, forced swim test; HPA, hypothalamic–pituitary–adrenal axis; OFT, open-field test; SPT, sucrose preference test; TST, tail suspension test; VO-Ohpic, VO-Ohpic trihydrate.