Antidepressant‐like effects of 20(S)‐protopanaxadiol in a mouse model of chronic social defeat stress and the related mechanisms

Abstract

20(S)-Protopanaxadiol (PPD) is a basic aglycone of the dammarane triterpenoid saponins and exerts antidepressant-like effects on behaviour in the forced swimming test (FST) and tail suspension test (TST) and in rat olfactory bulbectomy depression models.However, the antidepressant effects of PPD have not been studied thoroughly. The objective of the present study was first to investigate the effect of PPD on depression behaviours induced by chronic social defeat stress (CSDS) in mice. The results showed that CSDS was effective in producing depression-like behaviours in mice, as indicated by decreased responses in the social interaction test, sucrose preference test, TST, and FST, and that this effect was accompanied by noticeable alterations in the levels of oxidative markers (superoxide dismutase, catalase, and lipid peroxidation) and monoamines (5-HT and NE) in the hippocampus and serum corticosterone levels.Additionally, western blot analysis revealed that CSDS exposure significantly downregulated BDNF, p-TrkB/TrkB, p-Akt/Akt, and p-mTOR/mTOR protein expression in the hippocampus. Remarkably, chronic PPD treatment significantly ameliorated these behavioral and biochemical alterations associated withCSDS-induced depression.Our results suggest that PPD exerts antidepressant-like effects in mice with CSDSinduced depression and that this effect may be mediated by the normalization of neurotransmitter and corticosterone levels and the alleviation of oxidative stress, as well as the enhancement of the PI3K/Akt/mTOR-mediated BDNF/TrkB pathway. KEYWORDS 20(S)-protopanaxadiol, antidepressant, BDNF/TrkB, chronic social defeat stress, mice, PI3K/Akt/ mTOR

The antidepressant‐like effects of Shen Yuan: Dependence on hippocampal BDNF–TrkB signaling activation in chronic social defeat depression‐like mice

“…The FST test results showed that SY improved the despair behavior in that SY significantly shortened the enhanced immobility durations in mice induced by CSDS. Collectively, we found that 4‐week CSDS induces a variety of depressive behavioral changes in animals, including anhedonia, social avoidance and despair behavior, consistent with previous studies (Jiang, Lv, Wang, Wang, et al, 2019). As expected, consecutive treatment with SY completely reversed these behavioral deficits.…”

“…The SPT was performed for a duration of three consecutive days, including a two‐day sugar water adaptation phase and a one‐day test phase (Jiang et al, 2019). On the first two days (at 9:00 a.m.), each mouse was concurrently presented with two bottles containing 100 ml of either 1% sucrose solution or tap water, the animals had access to food/liquids ad libitum, and the location of the water bottles was altered every 12 hrs to minimize potential location bias.…”

“…The levels of the stress hormone corticosterone (CORT) and the concentrations of monoamines (5‐HT, NE and DA) in the hippocampus were determined with commercial enzyme‐linked immunosorbent assay (ELISA) kits for mice (Jiancheng Institute of Biotechnology, Nanjing, China) according to the manufacturer's instructions (Jiang, Lv, Wang, Wang, et al, 2019).…”

Dammarane sapogenins attenuates stress‐induced anxiety‐like behaviors by upregulating ERK/CREB/BDNF pathways

“…The social interaction test (SIT) comprised two 150‐s trials (Lin et al, 2018). The apparatus is a social interaction open field arena (40 × 40 × 40 cm), made of a white plastic material, with an empty wire‐mesh plexiglas enclosure (7 × 10 × 40 cm) located in the social interaction (SI) zone (13.5 × 24.0 cm) (Jiang et al, 2019). In the first phase, each mouse was placed along the center of the opposite wall and allowed to explore freely for 150 s. In the second phase, the mouse was re‐introduced into the box located in the middle of one of the walls of the open field with an unfamiliar aggressor CD‐1 mouse (“target” conditions) and allowed to explore again for 150 s. The time that the experimental mouse spent in the interaction zone under target conditions, and when a target was absent, was recorded by a camera.…”

“…Western blotting was performed as previously reported (Jiang et al, 2019; Lu et al, 2018). The dissected hippocampus and PFC tissues were homogenized in RIPA (radioimmunoprecipitation assay buffer) with a protease and phosphatase inhibitor cocktail (Sigma Aldrich).…”