Xanthoceraside administration produces significant antidepressant effects in mice through activation of the hippocampal BDNF signaling pathway

2021 ◽  
pp. 135994
Author(s):  
Wei Guan ◽  
Jiang-Hong Gu ◽  
Chun-Hui Ji ◽  
Yue Liu ◽  
Wen-Qian Tang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Antidepressant Effects ◽  
Bdnf Signaling

scholarly journals d-Serine produces antidepressant-like effects in mice through suppression of BDNF signaling pathway and regulation of synaptic adaptations in the nucleus accumbens

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Zhenzhen Chen ◽  
Zhenyu Tang ◽  
Ke Zou ◽  
Zhihong Huang ◽  
Liuer Liu ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Nucleus Accumbens ◽  
Signaling Pathway ◽  
High Performance ◽  
Forced Swim Test ◽  
Tail Suspension Test ◽  
Antidepressant Effects ◽  
Chronic Social Defeat Stress ◽  
The Central Nervous System ◽  
Bdnf Signaling

Abstract Objective d-Serine is a crucial endogenous co-agonist of N-methyl-d-aspartate receptors (NMDARs) in the central nervous system and can affect the function of the brain derived neurotrophic factor (BDNF) system, which plays an essential role in modulating synaptic plasticity. The current study aimed to systematically evaluate the role and mechanisms of d-serine in depressive behavior in nucleus accumbens (NAc). Methods d-Serine concentration in the chronic social defeat stress (CSDS) model in NAc was measured using high-performance liquid chromatography (HPLC). The antidepressant-like effects of d-serine were identified using forced swim test (FST) and tail suspension test (TST) in control mice and then assessed in CSDS model. We applied social interaction and sucrose preference tests to identify the susceptibility of CSDS model. Western blotting was further performed to assess the changes of BDNF signaling cascade in NAc after CSDS and d-serine treatment. The BDNF signaling inhibitor (K252a) was also used to clarify the antidepressant-like mechanism of d-serine. Moreover, d-serine effects on synaptic plasticity in NAc were investigated using electrophysiological methods. Results d-Serine concentration was decreased in depression susceptible mice in NAc. d-Serine injections into NAc exhibited antidepressant-like effects in FST and TST without affecting the locomotor activity of mice. d-Serine was also effective in CSDS model of depression. Moreover, d-serine down-regulated the BDNF signaling pathway in NAc during CSDS procedure. Furthermore, BDNF signaling inhibitor (K252a) enhanced the antidepressant effects of d-serine. We also found that d-serine was essential for NMDARs-dependent long-term depression (LTD). Conclusion d-Serine exerts antidepressant-like effects in mice mediated through restraining the BDNF signaling pathway and regulating synaptic plasticity in NAc.

scholarly journals An Integrative Pharmacology-Based Pattern to Uncover the Pharmacological Mechanism of Ginsenoside H Dripping Pills in the Treatment of Depression

2021 ◽  
Vol 11 ◽  
Author(s):  
Libin Zhao ◽  
Rui Guo ◽  
Ningning Cao ◽  
Yingxian Lin ◽  
Wenjing Yang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Camp Signaling ◽  
Ginsenoside Rh2 ◽  
Ppi Network ◽  
Pharmacological Mechanism ◽  
Camp Signaling Pathway ◽  
Antidepressant Effects ◽  
Bdnf Signaling ◽  
Major Target ◽  
Tof Ms

Objectives: To evaluate the pharmacodynamical effects and pharmacological mechanism of Ginsenoside H dripping pills (GH) in chronic unpredictable mild stress (CUMS) model rats.Methods: First, the CUMS-induced rat model was established to assess the anti-depressant effects of GH (28, 56, and 112 mg/kg) by the changes of the behavioral indexes (sucrose preference, crossing score, rearing score) and biochemical indexes (serotonin, dopamine, norepinephrine) in Hippocampus. Then, the components of GH were identified by ultra-performance liquid chromatography-iron trap-time of flight-mass spectrometry (UPLC/IT-TOF MS). After network pharmacology analysis, the active ingredients of GH were further screened out based on OB and DL, and the PPI network of putative targets of active ingredients of GH and depression candidate targets was established based on STRING database. The PPI network was analyzed topologically to obtain key targets, so as to predict the potential pharmacological mechanism of GH acting on depression. Finally, some major target proteins involved in the predictive signaling pathway were validated experimentally.Results: The establishment of CUMS depression model was successful and GH has antidepressant effects, and the middle dose of GH (56 mg/kg) showed the best inhibitory effects on rats with depressant-like behavior induced by CUMS. Twenty-eight chemical components of GH were identified by UPLC/IT-TOF MS. Subsequently, 20(S)-ginsenoside Rh2 was selected as active ingredient and the PPI network of the 43 putative targets of 20(S)-ginsenoside Rh2 containing in GH and the 230 depression candidate targets, was established based on STRING database, and 47 major targets were extracted. Further network pharmacological analysis indicated that the cAMP signaling pathway may be potential pharmacological mechanism regulated by GH acting on depression. Among the cAMP signaling pathway, the major target proteins, namely, cAMP, PKA, CREB, p-CREB, BDNF, were used to verify in the CUMS model rats. The results showed that GH could activate the cAMP-PKA-CREB-BDNF signaling pathway to exert antidepressant effects.Conclusions: An integrative pharmacology-based pattern was used to uncover that GH could increase the contents of DA, NE and 5-HT, activate cAMP-PKA-CREB-BDNF signaling pathway exert antidepressant effects.

scholarly journals D-serine has antidepressant effects in mice through suppression of the BDNF signaling pathway and regulation of synaptic plasticity in the nucleus accumbens

2021 ◽  
Author(s):  
Zhenzhen Chen ◽  
Zhenyu Tang ◽  
Ke Zou ◽  
Zhihong Huang ◽  
Liuer Liu ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Signaling Pathway ◽  
Essential Role ◽  
Therapeutic Agent ◽  
Experimental Approach ◽  
Antidepressant Effects ◽  
The Central Nervous System ◽  
Bdnf Signaling ◽  
Electrophysiological Methods ◽  
Preference Tests

Background and Purpose: D-serine is a crucial endogenous co-agonist of NMDARs in the central nervous system and can affect the function of the BDNF system, which plays an essential role in modulating synaptic plasticity. The aim of the current investigation was to systematically evaluate the role and mechanisms of D-serine in depressive behavior in NAc. Experimental Approach: D-Serine concentration in the CSDS model in NAc was measured by HPLC. The antidepressant-like effects of D-serine were identified by the FST and TST in control mice, and then assessed in the CSDS model. We applied social interaction and sucrose preference tests to identify the susceptibility of CSDS model. Western blotting was further performed to assess the changes of BDNF signaling cascade in NAc after CSDS and D-serine treatment. The BDNF signaling inhibitor (K252a) was also used to clarify the antidepressant mechanism of D-serine. Moreover, effects of D-serine on synaptic plasticity in NAc were investigated by electrophysiological methods. Key Results: D-serine injections into the NAc exhibited antidepressant effects in the FST, TST and CSDS model. Next, D-serine down-regulated the BDNF signaling pathway in NAc during the CSDS procedure. Moreover, K252a enhanced the antidepressant effects of D-serine. We also found that D-serine was essential for NMDARs-LTD. Conclusion and Implications: Our results provide the first evidence that D-serine exerts antidepressant effects in mice mediated through restraining the BDNF signaling pathway and regulating synaptic plasticity in NAc, which indicates that D-serine may be an effective therapeutic agent for depression. KEYWORDS D-serine, depression, NAc, BDNF, CSDS, LTD

scholarly journals Mechanisms Underlying the Anti-Depressive Effects of Regular Tea Consumption

Nutrients ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 1361 ◽  
Author(s):  
Dylan O’Neill Rothenberg ◽  
Lingyun Zhang
Keyword(s):  
Antidepressant Activity ◽  
Black Tea ◽  
Tea Consumption ◽  
Major Pathway ◽  
Depression Risk ◽  
Microbiome Diversity ◽  
Antidepressant Effects ◽  
Bdnf Signaling ◽  
Risk Ratios

This article is a comprehensive review of the literature pertaining to the antidepressant effects and mechanisms of regular tea consumption. Meta-data supplemented with recent observational studies were first analyzed to assess the association between tea consumption and depression risk. The literature reported risk ratios (RR) were 0.69 with 95% confidence intervals of 0.62–0.77. Next, we thoroughly reviewed human trials, mouse models, and in vitro experiments to determine the predominant mechanisms underlying the observed linear relationship between tea consumption and reduced risk of depression. Current theories on the neurobiology of depression were utilized to map tea-mediated mechanisms of antidepressant activity onto an integrated framework of depression pathology. The major nodes within the network framework of depression included hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, inflammation, weakened monoaminergic systems, reduced neurogenesis/neuroplasticity, and poor microbiome diversity affecting the gut–brain axis. We detailed how each node has subsystems within them, including signaling pathways, specific target proteins, or transporters that interface with compounds in tea, mediating their antidepressant effects. A major pathway was found to be the ERK/CREB/BDNF signaling pathway, up-regulated by a number of compounds in tea including teasaponin, L-theanine, EGCG and combinations of tea catechins and their metabolites. Black tea theaflavins and EGCG are potent anti-inflammatory agents via down-regulation of NF-κB signaling. Multiple compounds in tea are effective modulators of dopaminergic activity and the gut–brain axis. Taken together, our findings show that constituents found in all major tea types, predominantly L-theanine, polyphenols and polyphenol metabolites, are capable of functioning through multiple pathways simultaneously to collectively reduce the risk of depression.

Sign in / Sign up

Export Citation Format

Share Document