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 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

Gemfibrozil has antidepressant effects in mice: Involvement of the hippocampal brain-derived neurotrophic factor system

2018 ◽  
Vol 32 (4) ◽  
pp. 469-481 ◽  
Author(s):  
Yu-Fei Ni ◽  
Hao Wang ◽  
Qiu-Yan Gu ◽  
Fei-Ying Wang ◽  
Ying-Jie Wang ◽  
...  
Keyword(s):  
Neurotrophic Factor ◽  
Forced Swim Test ◽  
Preference Test ◽  
Tail Suspension Test ◽  
Brain Derived Neurotrophic Factor ◽  
Peroxisome Proliferator ◽  
Mild Stress ◽  
Peroxisome Proliferator Activated Receptor ◽  
Antidepressant Effects ◽  
Bdnf Signaling

Major depressive disorder has become one of the most serious neuropsychiatric disorders worldwide. However, currently available antidepressants used in clinical practice are ineffective for a substantial proportion of patients and always have side effects. Besides being a lipid-regulating agent, gemfibrozil is an agonist of peroxisome proliferator-activated receptor-α (PPAR-α). We investigated the antidepressant effects of gemfibrozil on C57BL/6J mice using the forced swim test (FST) and tail suspension test (TST), as well as the chronic unpredictable mild stress (CUMS) model of depression. The changes in brain-derived neurotrophic factor (BDNF) signaling cascade in the brain after CUMS and gemfibrozil treatment were further assessed. Pharmacological inhibitors and lentivirus-expressed short hairpin RNA (shRNA) were also used to clarify the antidepressant mechanisms of gemfibrozil. Gemfibrozil exhibited significant antidepressant actions in the FST and TST without affecting the locomotor activity of mice. Chronic gemfibrozil administration fully reversed CUMS-induced depressive-like behaviors in the FST, TST and sucrose preference test. Gemfibrozil treatment also restored CUMS-induced inhibition of the hippocampal BDNF signaling pathway. Blocking PPAR-α and BDNF but not the serotonergic system abolished the antidepressant effects of gemfibrozil on mice. Gemfibrozil produced antidepressant effects in mice by promoting the hippocampal BDNF system.

scholarly journals Δ3,2-Hydroxybakuchiol Attenuates Depression in Multiple Rodent Models Possibly by Inhibition of Monoamine Transporters in Brain

2018 ◽  
Vol 2018 ◽  
pp. 1-10
Author(s):  
Gang Zhao ◽  
Li-he Guo ◽  
Wei Huang ◽  
Jia-liang Hu
Keyword(s):  
Forced Swim Test ◽  
Tail Suspension Test ◽  
Rat Striatum ◽  
Mild Stress ◽  
Monoamine Transporters ◽  
Rodent Models ◽  
Norepinephrine Concentration ◽  
Antidepressant Effects ◽  
Immobility Time ◽  
Pheochromocytoma Pc12

Δ3,2-Hydroxybakuchiol is isolated fromPsoralea corylifolia (L.), which has therapeutic applications in traditional Chinese medicine. Our previous studies have showed that Δ3,2-hydroxybakuchiol inhibited the decreased activity of reserpinized mice, suggestive of its antidepressive potential. In this study, we explored the antidepressant profile of Δ3,2-hydroxybakuchiol in various rodent models and its possible monoamine-modulating mechanism. Δ3,2-Hydroxybakuchiol significantly reduced immobility time of mice in forced swim test and tail suspension test. Δ3,2-Hydroxybakuchiol also significantly increased sucrose consumption in chronic unpredictable mild stress (CUMS) rat model. Furthermore, isotope uptake study showed that Δ3,2-hydroxybakuchiol inhibited the activity of human dopamine transporter (DAT) and norepinephrine transporter (NET) in transporter-overexpressing pheochromocytoma (PC12) cells with IC50values similar to the potency of bupropion. Microdialysis showed that Δ3,2-hydroxybakuchiol increased dopamine and norepinephrine concentration in rat striatum. In summary, Δ3,2-hydroxybakuchiol exerts antidepressant effects on various types of depression models through a possible mechanism of monoamine transporter inhibition.

scholarly journals Immediate and persistent antidepressant-like effects of Chaihu-jia-Longgu-Muli-tang are associated with instantly up-regulated BDNF in the hippocampus of mice

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Xing Wang ◽  
Jie Chen ◽  
Hailou Zhang ◽  
Zhiheng Huang ◽  
Zhilu Zou ◽  
...  
Keyword(s):  
Single Dose ◽  
Forced Swim Test ◽  
Antidepressant Activity ◽  
Tail Suspension Test ◽  
Primary Role ◽  
Single Administration ◽  
Bdnf Expression ◽  
Clinical Dose ◽  
Swim Test ◽  
Antidepressant Effects

AbstractConventional antidepressants have a disadvantage in delayed onset of efficacy. Here, we aimed to evaluate the immediate and persistent antidepressant-like action of a classic herbal medicine Chaihu-jia-Longgu-Muli decoction (CLM) as well as the action of CLM on hippocampal brain-derived neurotrophic factor (BDNF) over time. CLM consists of Xiaochaihu decoction (XchD), Longgu-Muli (LM) and several other herbs. The contribution of constituent herbal formula XchD and other parts of CLM was also assessed. Following a single dose of CLM, tail suspension test (TST), forced swim test (FST), and novelty-suppressed feeding test (NSF) were performed. The antidepressant activity of XchD, its interaction with LM or remaining parts of CLM was also examined after a single administration. BDNF expression in the hippocampus was examined at 30 min and 24 hr post a single CLM. A single administration of half of clinical dose of CLM elicited antidepressant effects at TST 30 min post administration, and lasted for 72 hr. Furthermore, CLM also reduced the latency to eat in NSF test. A single proportional dose of XchD induced antidepressant effects at 30 min and lasted for 48 hr, whereas the effect lasted for 72 hr when combined with either LM or the remaining parts of CLM. BDNF expression increased at 30 min and persisted at least for 24 hr after a single dose of CLM. The results support that Chaihu-jia-Longgu-Muli decoction was capable to immediately and enduringly elicit antidepressant activity via enhancement of hippocampal BDNF expression, in which the constituent Xiaochaihu decoction played the primary role.

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