Loganin exerts antidepressant-like effects via Sigma-1R- and
BACKGROUND AND PURPOSE Sigma-1 receptor (Sigma-1R), a chaperone protein
with the ability to activate brain-derived neurotrophic factor (BDNF)
signaling, has been connected with antidepressant action. Our previous
study indicated that loganin has antidepressant-like effects. This study
aimed to investigate whether loganin exerts antidepressant-like effects
via Sigma-1R/BDNF signaling. EXPERIMENTAL APPROACH We established rat
model of depression using chronic unpredictable stress (CUS). Sucrose
preference test (SPT) and open field test (OFT) were used to evaluate
the antidepressant-like effects of loganin. Then, we assessed the
changes of BDNF signaling, synaptic plasticity and neurogenesis in
hippocampus using western blot and immunohistochemical analysis. To
confirm the role of Sigma-1R and BDNF in loganin-induced
antidepressant-like effects, BD1047 and ANA-12 were used to block
Sigma-1R and BDNF, respectively. KEY RESULTS Loganin improved
depressive-like behaviors of rats in the SPT and OFT.
Antidepressant-like effects of loganin in the SPT occur at day 6, which
was faster than fluoxetine. Mechanismly, loganin effectively restored
CUS-induced decrease in BDNF, pERK/1/2, PSD-95 and DCX in the
hippocampus. Blockage of BDNF signaling with ANA-12 reversed the
antidepressant-like effects of loganin. Moreover, loganin exhibited a
binding affinity with Sigma-1R, as indicated by molecular docking.
Importantly, BD1047 diminished loganin-induced improvement of rat
behaviors as well as activation of hippocampal BDNF signaling.
CONCLUSIONS AND IMPLICATIONS In conclusion, loganin exerts
antidepressant-like effects by improving synaptic plasticity and
neurogenesis in the hippocampus dependent on Sigma-1R/BDNF signaling.