Fig. 3: Pharmacological degradation of hippocampal PNN replicates the rapid antidepressant action of VLX + EE treatment.

A, B Experimental timeline. Animals were exposed to corticosterone (CORT mice, n = 35) in the drinking water throughout the experiment. From week 0, CORT mice were received venlafaxine or vehicle for 2 weeks in their home cage (CORT-VEH mice, n = 9 and CORT-VLX mice, n = 8). These groups were divided into two additional groups receiving intra-hippocampal injections of the PNN degrading enzyme ChABC, or vehicle. (CORT-VEH mice: n = 9, CORT-VLX mice: n = 8, CORT-ChABC mice: n = 9; and CORT-VLX-ChABC mice: n = 9). C Proportion of PV+/PNN+ cells among PV+ cells in CA1. One-way ANOVA with treatment as main factor revealed a significant effect of treatment (F_(3;31) = 11.00, p < 0.001). Emotional (D) and cognitive (E) z-scores were calculated and a two-way ANOVA with pre-treatment (VLX vs. VEH) and treatment (ChABC vs. vehicle) factors was applied. For the emotional z-score, a significant effect of pre-treatment (VLX vs. VEH) and treatment factors (ChABC vs. VEH) but not of their interaction was unveiled (F_(1;31) = 9.06, p < 0.01, F_(1;31) = 47.0, p < 0.001, F_(1;31) = 1.08, p = 0.301, respectively). For the cognitive z-score (E), a significant effect of treatment but not of pre-treatment nor their interaction was unveiled (F_(1;31) = 41.7, p < 0.001, F_(1;31) = 0.05, p = 0.824, F_(1;31) = 0.00, p = 0.985, respectively). Data represent mean ± SEM, dots illustrate individual values. Post-hoc analysis when appropriate: **p < 0.01, ***p < 0.001 indicate significant difference compared to CORT-VEH group. ^$p < 0.05 indicates significant difference compared to CORT-ChABC group. ^###p < 0.001 indicates significant difference compared to CORT-VLX group.