Fig. 3

Early psilocybin intervention modifies BDNF and TrkB levels and selectively stimulates the ERK, Akt, and mTOR signaling cascades in various brain regions. (A) Circulating levels of BDNF in blood serum were quantified using the Luminex assay. Circulating BDNF levels in the SIS-Sham rats were significantly lower than those in the CTL rats, whereas circulating BDNF levels in the SIS-PSI rats were significantly elevated compared to those in the SIS-Sham rats. The sample sizes were CTL, n = 5; SIS-Sham, n = 7; and SIS-PSI, n = 7. The data are presented as the mean ± SEM (**p < 0.01) and were analyzed by one-way ANOVA followed by Tukey’s post hoc test. (B) Representative WB images illustrating the expression of BDNF, TrkB, p-ERK/ERK, p-Akt/Akt, and p-mTOR/mTOR in the prefrontal cortex (PFC), amygdala (AMG), hippocampus (HIP), and hypothalamus (HYP) of WKY rats exposed to SIS, with GAPDH serving as a loading control. (C) Quantification of BDNF levels in all four brain regions: In the PFC, HIP, and HYP, the BDNF levels were significantly greater in the SIS-PSI rats than in the SIS-Sham rats. In the AMG, a marginal but nonsignificant increase in BDNF was observed in the SIS-PSI rats compared to the SIS-Sham rats. (D) Quantification of TrkB levels in all four brain regions: SIS-PSI rats showed notable upregulation of TrkB expression in the AMG and HIP. Increases in TrkB levels in the PFC and HYP were less pronounced. (E) Quantification of p-ERK/ERK levels in all four brain regions: Increased phosphorylation of ERK was significantly observed in the PFC and HYP of the SIS-PSI rats compared to those in the SIS-Sham rats. A minor and nonsignificant increase was noted in the AMG and HIP. (F) Quantification of p-Akt/Akt levels in all four brain regions: a significant increase in Akt phosphorylation in the HIP was observed in the SIS-PSI rats, with only slight and nonsignificant increases observed in the PFC, AMG, and HYP. (G) Quantification of p-mTOR/mTOR levels in all four brain regions: SIS-PSI rats demonstrated significantly heightened mTOR phosphorylation exclusively in the HIP, with minor and nonsignificant increases in the other three brain regions. The sample sizes for the SIS-Sham and SIS-PSI groups (C-G) were 5 for each group. The data are presented as the mean ± SEM († p < 0.05, †† p < 0.01) and were analyzed using multiple unpaired t-tests.