Treatment with PEA activates BDNF/TrkB signaling in CORT-induced mice. (A) PEA restores the mRNA levels of BDNF and TrkB in CORT-induced mice. Mice were exposed with either CORT (20 mg/kg) or saline (control) once a day for 21 days. After 17 days of initial administration, the mice received daily treatment of PEA (50 mg/kg) or imipramine (10 mg/kg) during an additional 4 days of CORT exposure. The mRNA levels of BDNF and TrkB were assessed by RT-PCR in hippocampus. (B,C) Quantification of mRNA levels shown in (A). The levels of mRNA were normalized to GAPDH transcription. n = 3 independent tissue using three mice. Statistical significance was determined by two-way ANOVA with Bonferroni correction test. Data are shown as relative changes versus controls. * p < 0.05, ** p < 0.01. (D) PEA restores the levels of BDNF and TrkB proteins in CORT-induced mice. (E,F) Quantification of protein levels shown in (D). The levels of protein were normalized to β-actin expression. n = 3 independent tissue using three mice. Statistical significance was determined by two-way ANOVA with Bonferroni correction test. Data are shown as relative changes versus controls. ** p < 0.01, *** p < 0.001. (G) PEA rescues the mRNA levels of PSD95 and SYP in CORT-induced mice. (H,I) Quantification of mRNA levels shown in (G). The levels of mRNA were normalized to GAPDH transcription. n = 3 independent cultures using three mice. Statistical significance was determined by two-way ANOVA with Bonferroni correction test. Data are shown as relative changes versus controls. ** p < 0.01, *** p < 0.001. (J) PEA restores the levels of PSD95 and SYP proteins in CORT-induced mice. (K,L) Quantification of protein levels shown in (J). The levels of protein were normalized to β-actin expression. n = 3 independent tissue using three mice. Statistical significance was determined by two-way ANOVA with Bonferroni correction test. Data are shown as relative changes versus controls. * p < 0.05, ** p < 0.01, *** p < 0.001.