Aim of the study
We aimed to assess the rapid antidepressant potential of JWX, within the prescription dose range, and the distinct underlying neuroplasticity signaling mechanism. Materials and
Conclusion
JWX elicits a rapid antidepressant effect, via quickly stimulating CaMKII signaling, subsequently activating mTOR-BDNF signaling pathway, and thus enhancing hippocampal neuroplasticity.
Methods
The rapid antidepressant response of JWX were determined using various behavioral paradigms, and in a corticosterone (CORT)-induced depression model in mice. The molecular neuroplasticity signaling and the expression of BDNF in the hippocampus was evaluated using immunoblotting and immunostaining. The contribution of specific signaling was investigated using pharmacological interventions.
Results
A single dose of JWX induced rapid and persistent antidepressant effects in both the normal and chronic CORT-exposed mice. The phosphorylation of CaMKII, mTOR, ERK and the expressions of BDNF, synapsin1 and PSD95 increased at 30 min post JWX. JWX restored the expression of BDNF in the hippocampal dentate gyrus reduced by CORT-exposure. The rapid antidepressant effect and upregulation of BDNF expression by JWX was blunted by a mTOR antagonist, rapamycin, or a CaMKII antagonist, KN-93. CaMKII signaling blockade blunted mTOR signaling activated by JWX, but not vice versa.