scholarly journals Electroacupuncture Ameliorates Depression-Like Behaviour in Rats by Enhancing Synaptic Plasticity via the GluN2B/CaMKII/CREB Signalling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Kun Zhang ◽  
Ran Liu ◽  
Jingruo Zhang ◽  
Xifang Wei ◽  
Yuan Gao ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Preference Test ◽  
Pathological Process ◽  
Signalling Pathway ◽  
Mild Stress ◽  
Nissl Staining ◽  
Beneficial Effects ◽  
Protein Levels ◽  
Immobility Time ◽  
Sucrose Preference Test

Background. Hippocampal synaptic plasticity during the pathological process of depression has received increasing attention. Hippocampal neuron atrophy and the reduction in synaptic density induced by chronic stress are important pathological mechanisms of depression. Electroacupuncture (EA) exerts beneficial effects on depression, but the mechanism is unclear. This study explored the effect of EA on synaptic plasticity and the potential mechanism. Methods. Forty-eight SD rats were randomly divided into the control, chronic unpredictable mild stress (CUMS), EA, and fluoxetine (FLX) groups, and each group consisted of 12 rats. The sucrose preference test, open field test, and forced swimming test were used for the evaluation of depression-like behaviour, and Golgi and Nissl staining were used for the assessment of synaptic plasticity. Western blotting and immunofluorescence were conducted to detect proteins related to synaptic plasticity and to determine their effects on signalling pathways. Results. We found that CUMS led to depression-like behaviours, including a reduced preference for sucrose, a prolonged immobility time, and reduced exploration activity. The dendritic spine densities and neuron numbers and the protein levels of MAP-2, PSD-95, and SYN were decreased in the hippocampi of rats with CUMS-induced depression, and these trends were reversed by EA. The molecular mechanism regulating this plasticity may involve the GluN2B/CaMKII/CREB signalling pathway. Conclusion. These results suggest that EA can improve depression-like behaviour and hippocampal plasticity induced by CUMS, and the mechanism may be related to the GluN2B/CaMKII/CREB pathway.

scholarly journals The Combination of Aquilaria sinensis (Lour.) Gilg and Aucklandia costus Falc. Volatile Oils Exerts Antidepressant Effects in a CUMS-Induced Rat Model by Regulating the HPA Axis and Levels of Neurotransmitters

2021 ◽  
Vol 11 ◽  
Author(s):  
Huiting Li ◽  
Yuanhui Li ◽  
Xiaofei Zhang ◽  
Guilin Ren ◽  
Liangfeng Wang ◽  
...  
Keyword(s):  
Hpa Axis ◽  
Central Area ◽  
Preference Test ◽  
Volatile Oil ◽  
Antidepressant Effect ◽  
Mild Stress ◽  
Aquilaria Sinensis ◽  
Immobility Time ◽  
The Central Nervous System ◽  
Sucrose Preference Test

The Aquilaria sinensis (Lour.) Gilg (CX)–Aucklandia costus Falc. (MX) herbal pair is frequently used in traditional Chinese medicine prescriptions for treating depression. The volatile oil from CX and MX has been shown to have good pharmacological activities on the central nervous system, but its curative effect and mechanism in the treatment of depression are unclear. Therefore, the antidepressant effect of the volatile oil from CX–MX (CMVO) was studied in chronic unpredictable mild stress (CUMS) rats. The suppressive effects of CMVO (25, 50, 100 μL/kg) against CUMS-induced depression-like behavior were evaluated using the forced swimming test (FST), open field test (OFT) and sucrose preference test (SPT). The results showed that CMVO exhibited an antidepressant effect, reversed the decreased sugar preference in the SPT and prolongation of immobility time in the FST induced by CUMS, increased the average speed, time to enter the central area, total moving distance, and enhanced the willingness of rats to explore the environment in the OFT. Inhalational administration of CMVO decreased levels of adrenocorticotropic hormone and corticosterone in serum and the expression of corticotropin-releasing hormone mRNA in the hypothalamus, which indicated regulation of over-activation of the hypothalamic–pituitary–adrenal (HPA) axis. In addition, CMVO restored levels of 5-hydroxytryptamine (5-HT), dopamine, norepinephrine and acetylcholine in the hippocampus. The RT-PCR and immunohistochemistry results showed that CMVO up-regulated the expression of 5-HT1A mRNA. This study demonstrated the antidepressant effect of CMVO in CUMS rats, which was possibly mediated via modulation of monoamine and cholinergic neurotransmitters and regulation of the HPA axis.

Electroacupuncture Prevents the Depression-Like Behavior by Inhibiting the NF-κB/NLRP3 Inflammatory Pathway in Hippocampus of Mice Subjected to Chronic Mild Stress

2022 ◽  
pp. 1-9
Author(s):  
Qi Wang ◽  
Hongsheng Bi ◽  
Hongfei Huang ◽  
Yitong Wang ◽  
Lili Gong ◽  
...  
Keyword(s):  
Chronic Mild Stress ◽  
Preference Test ◽  
Underlying Mechanism ◽  
Sucrose Preference ◽  
Receptor Protein ◽  
Mild Stress ◽  
Inflammatory Pathway ◽  
Protein Levels ◽  
Tnf Α ◽  
Immobility Time

<b><i>Background:</i></b> The precise physiological mechanisms of acupuncture in the treatment of depression are still unknown. This study aimed to observe the effects of electroacupuncture (EA) on depression-like behavior of mouse in chronic mild stress (CMS) model and explore the underlying mechanism. <b><i>Methods:</i></b> The depression model was established by using CMS method for 6 weeks. After the third week of the CMS paradigm, EA treatment was performed daily for 15 min over a period of 3 weeks. The antidepressant-like effects of EA were evaluated using the sucrose preference test and the forced swimming test (FST). The protein levels of the nuclear factor-kappa B (NF-κB), p-NF-κB, inhibitor of NF-κB, p-IκBα, NOD-like receptor protein 3, interleukin (IL)-6, IL-1β, IL-18, and tumor necrosis factor-α (TNF-α) in hippocampus of mice were detected. <b><i>Results:</i></b> Sucrose preference was decreased after 6 weeks of CMS and the effects of CMS was reversed by EA. CMS increased immobility time and decreased latency to the first immobility in the FST test, but these effects were reversed by EA. CMS-induced nuclear entry of NF-κB (nuclear/cytoplasmic ratio of NF-κB) with an increase in protein levels of p-NF-κB and p-IκBα in the hippocampus. The CMS also increased NLRP3 levels in the hippocampus. However, these effects were reversed by EA. In addition, the levels of IL-6, IL-1β, IL-18, and TNF-α in the hippocampus were increased by CMS, and these effects of stress were reversed by EA. <b><i>Conclusion:</i></b> EA prevented CMS-induced depressive-like behaviors by inhibiting NF-κB/NLRP3 inflammatory pathway.

scholarly journals The Antidepressant-Like Effects of Shen Yuan in a Chronic Unpredictable Mild Stress Rat Model

2021 ◽  
Vol 12 ◽  
Author(s):  
Ning Jiang ◽  
Haixia Wang ◽  
Hong Huang ◽  
Jingwei Lv ◽  
Guirong Zeng ◽  
...  
Keyword(s):  
Panax Ginseng ◽  
Forced Swim Test ◽  
Preference Test ◽  
Underlying Mechanism ◽  
Mild Stress ◽  
Chronic Unpredictable Mild Stress ◽  
Oxidative Markers ◽  
Immobility Time ◽  
Polygala Tenuifolia ◽  
Sucrose Preference Test

Depression is a common yet severe neuropsychiatric condition that causes imposes considerable personal, economic, and social burdens worldwide. Medicinal plant species (e.g., Panax ginseng and Polygala tenuifolia) demonstrate potent antidepressant-like effects with less toxicity and other side effects. Shen yuan prescription (SY), composed of Panax ginseng (GT) and Polygala tenuifolia (YT). The present study aimed to elucidate the effects of SY treatment on chronic unpredictable mild stress (CUMS) rats and study the underlying mechanism. Our results indicated that SY (67.5, 135, or 270 mg/kg) significantly reverses the depressive-like behaviors in rats with a 5-week CUMS exposure, as demonstrated by increased sucrose consumption in the sucrose preference test, and decreased immobility time in the tail suspension and forced swim test. Moreover, SY altered serum corticosterone levels, pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α), and oxidative markers (SOD, CAT, and MDA), and increased the levels of hippocampal neurotransmitters (5-HT, DA, and NE) in rats exposed to CUMS. Furthermore, rats treated with SY showed a reduction in the protein expression of BDNF, p-TrkB, p-Akt, and p-mTOR proteins induced by CUMS exposure in the hippocampus. In conclusion, SY prevented depressive-like behaviors in CUMS-exposed rats by preventing hypothalamus-pituitary-adrenal axis dysfunction, decreasing the levels of the neurotransmitters, minimizing oxidative stress, suppressing neuroinflammation, and activating the PI3K/Akt/mTOR-mediated BDNF/TrkB pathway, all of which are the key players in the pathological basis of depression.

scholarly journals Electroacupuncture Reverses CUMS-Induced Depression-Like Behaviors and LTP Impairment in Hippocampus by Downregulating NR2B and CaMK II Expression

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Shuo Jiang ◽  
Zui Shen ◽  
Wenlin Xu
Keyword(s):  
Synaptic Plasticity ◽  
Global Mental Health ◽  
Hippocampal Slices ◽  
Preference Test ◽  
Long Term Potentiation ◽  
Antidepressant Effect ◽  
Feeding Time ◽  
Mild Stress ◽  
Protein Levels ◽  
Behavior Of Rats

Objective. Depression is a global mental health problem with high disability rate, which brings a huge disease burden to the world. Electroacupuncture (EA) has been shown to be an effective method for the treatment of depression. However, the mechanism underling the antidepressant effect of EA has not been clearly clarified. The change of synaptic plasticity is the focus in the study of antidepressant mechanism. This study will observe the effect of EA on LTP of hippocampal synaptic plasticity and explore its possible mechanism. Methods. The depression-like behavior rat model was established by chronic unpredictable mild stress (CUMS). EA stimulation (Hegu and Taichong) was used to treat the depressed rats. The depression-like behavior of rats was tested by weight measurement, open field test, depression preference test, and novelty suppressed feeding test. Long-term potentiation (LTP) was recorded at CA1 synapses in hippocampal slices by electrophysiological method. N-methyl-D-aspartate receptor subunit 2B (NR2B) and calmodulin-dependent protein kinase II (CaMK II) protein levels were examined by using western blot. Results. After the establishment of CUMS-induced depression model, the weight gain rate, sucrose preference rate, line crossing number, and rearing times of rats decreased, and feeding time increased. At the same time, the LTP in hippocampus was impaired, and the expressions of NR2B and CaMK II were upregulated. After EA treatment, the depression-like behavior of rats was improved, the impairment of LTP was reversed, and the expression levels of NR2B and CaMK II protein were downregulated. Conclusion. EA can ameliorate depression-like behaviors by restoring LTP induction, downregulating NR2B and CaMK II expression in CUMS model rats, which might be part of the mechanism of EA antidepressant.

scholarly journals Emodin Prevented Depression in Chronic Unpredicted Mild Stress Exposured Rats by Targeting MiR139-5p/5-Lipoxygenase

2021 ◽  
Author(s):  
Teng Zhang ◽  
Can Yang ◽  
Jiang Chu ◽  
Linna Ning ◽  
Peng Zeng ◽  
...  
Keyword(s):  
Psychosocial Stress ◽  
Inflammatory Responses ◽  
Glycogen Synthase ◽  
Preference Test ◽  
Underlying Mechanism ◽  
Related Factor ◽  
Mild Stress ◽  
Nissl Staining ◽  
Force Swimming Test ◽  
Sucrose Preference Test

Abstract Background: Using ingredients of medicinal plants is one of the goals of developing potential drugs for treating depression. Compelling evidences suggested anti-inflammation might block the occurrence of depression. Here, the effect of a natural compound, emodin, on the developing of psychosocial stress-induced depression and the underlying mechanism were studied.Methods: 7 weeks’ chronic unpredicted mild stress (CUMS) were performed to replicate psychosocial stress in rats, and sucrose preference test, force swimming test and open field test were used to evaluate their behaviors. The differentially expressed proteins in hippocampus were analyzed by proteomics. Nissl staining and Golgi staining were used to detect the losses of neurons and synapses, immunohistochemical staining was used to detect the activation of microglia, and ELISA was used to detect the levels of pro-inflammatory cytokines. Western blotting, immunofluorescence and quantitative PCR were also included.Results: Hippocampal inflammation with up-regulated 5-lipoxygenase (5-LO) was observed in the depressed rats after CUMS exposure. And the up-regulation of 5-LO was proved to be caused by the decrease of miR139-5p. To observe the effect of emodin, we screened out depression susceptible (DeS) rats during CUMS and treated them with emodin (80mg/kg/day). 2 weeks later, emodin obviously prevented the depression behaviors of DeS rats and a series of pathological changes in their hippocampi, such as losses of neurons and spines, microglia activation, increased interleukin-1b and tumor necrosis factor-a, and the activation of 5-LO. Furtherly, we demonstrated that emodin inhibited its excess inflammatory responses possibly by targeting miR139-5p/5-LO and modulating the downstream glycogen synthase kinase 3β and nuclear factor erythroid 2-related factor 2. Conclusions: These results provided an important evidence that emodin may be a candidate agent for the treatment of depression and established a key role of miR139-5p/5-LO in the inflammation of depression.

scholarly journals Lycopene Treatment Transposed Antidepressant-Like Action in Rats Provoked to Chronic Mild Stress

2019 ◽  
Vol 12 (2) ◽  
pp. 981-988
Author(s):  
Venkata Naveen Kumar P. ◽  
Elango P. ◽  
Asmathulla S. ◽  
Kavimani S
Keyword(s):  
Open Field ◽  
Elevated Plus Maze ◽  
Forced Swim Test ◽  
Chronic Mild Stress ◽  
Preference Test ◽  
Behavioral Changes ◽  
Mild Stress ◽  
Plus Maze ◽  
Immobility Time ◽  
Sucrose Preference Test

The present study aimed at evaluating the effects of lycopene on CMS-induced depressive-like behavioral changes in Wistar rats. In present study, rodents were selected randomly and grouped in to seven groups. Each group consists of six animals. All the groups are subjected to chronic mild stress in an unpredictable manner except the control group, which is free from stress. Behavioral changes induced during chronic mild stress were assessed by conducting the behavioral tests like forced swim test, sucrose preferences test, elevated plus maze test and open field tests in screening depressant and anxiety activity. The data analysis showed chronic mild stress produced depressive and anxiogenic behavior in the experimental rats. A significant increase in the immobility time and decrease in sucrose consumption in sucrose preference test are noted in CMS and vehicle groups. Similarly, in an elevated plus maze a significant decrease in the entries in the open arm and decrease in central square entries, and rearing behavior and increase in the duration of immobility were observed in open field test.Lycopene treatment for 6-weeks significantly decreased immobility time and increased in sucrose consumption observed in the forced swim test and sucrose preference test respectively. Lycopene significantly increased number of entries in the open arm of elevated plus maze and decreased grooming and freezing behavior in open field method. lycopene supplemented dose of 5mg/kg showed an insignificant results in all the behavioral models (p>0.05).The data were expressed as Mean±SD.Data were analyzed and differences between the means were determined by one-way analysis of variance (ANOVA) Using graph pad prism version 5.03 statistical software. In all the tests, differences were considered significant if p<0.05 to be a statistical significant. lycopene possesses antidepressant and mild- anxiolytic activity which may be due to its antioxidant effect that might warrant further studies.

scholarly journals An experimental study to evaluate the role of aspirin and metformin in prevention of depression in rats

2020 ◽  
Vol 9 (4) ◽  
pp. 605
Author(s):  
Alisha Abbas ◽  
Narendra Kumar ◽  
Sarvesh Singh ◽  
Rahul Kumar ◽  
Akhlaque Ahmad ◽  
...  
Keyword(s):  
Forced Swim Test ◽  
Preference Test ◽  
Sucrose Preference ◽  
Mild Stress ◽  
Neurotransmitter System ◽  
Treatment Focus ◽  
Immobility Time ◽  
Current Therapies ◽  
Sucrose Preference Test

Background: Depression was seen to be associated with an increased level of inflammatory biomarkers along with the disturbance in the monoamine neurotransmitter system. Current therapies are mostly focussed on the neurotransmitters imbalance but due to increasing cases of treatment failure there is a need to shift our treatment focus to other potential therapies. This study aimed to evaluate the preventive role of aspirin and metformin in stress induced model of depression in wistar rats.Methods: Fifty four wistar rats were randomly divided into nine groups as normal control, experimental control, aspirin (30 mg/kg, 60 mg/kg), metformin (50 mg/kg, 100 mg/kg), two combination groups and imipramine (15 mg/kg). Depression model was created by the induction of chronic unpredictable mild stress (CUMS) for consecutive 28 days. Behavioural assessment was done by evaluating immobility time in forced swim test (FST) and sucrose preference ratio (SPR) in sucrose preference test. The data were analysed by analysis of variance (ANOVA) test using SPSS software. P<0.05 was considered to be statistically significant.Results: The CUMS led to an increase in immobility time and decrease in SPR. Aspirin and Metformin alone and their combinations showed statistically significant response in preventing the immobility time to increase (p<0.001) and SPR to decrease (p<0.001). However the response of Aspirin was comparable with Imipramine but the response of Metformin was not as significant as of Imipramine (p>0.05).Conclusions: Aspirin and metformin might have a potential role in the prevention of depression.

scholarly journals The Effect of Early Maternal Separation Combined With Adolescent Chronic Unpredictable Mild Stress on Behavior and Synaptic Plasticity in Adult Female Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiawen Huang ◽  
Chongkun Shen ◽  
Ran Ye ◽  
Yafei Shi ◽  
Weirong Li
Keyword(s):  
Synaptic Plasticity ◽  
Adult Female ◽  
Maternal Separation ◽  
Antidepressant Drug ◽  
Preference Test ◽  
Synaptic Proteins ◽  
Female Rats ◽  
Mild Stress ◽  
Chronic Unpredictable Mild Stress ◽  
Nissl Staining

Our aims were to evaluate the depression model of early maternal separation (MS) combined with adolescent chronic unpredictable mild stress (CUMS) in female adult SD rats to observe the behavior and the expressions of synaptic proteins in rats and to provide a reference for the screening of antidepressant drug activity. In our study, MS and CUMS were conducted to establish a dual stress model on female rats. Behavioral tests, including the sucrose preference test, open field test, and zero maze test, were used to detect depression-like and anxiety-like behavior of animals. Nissl staining was used to detect the number of neuronal cells in the hippocampus CA1 and DG regions of rats from each group. Synaptophysin (SYN), postsynaptic density-95 (PSD-95), and growth-associated protein-43 (GAP-43) expressions in the hippocampus were detected by western blot. Expression of the hippocampus SYN protein was further detected by immunohistochemistry. Rats in the MS+CUMS group presented more serious depression-like and anxiety-like behavior than in the MS group. Also, few Nissl bodies in the hippocampus CA1 and DG regions, less percentage of SYN-positive cells, and downregulated expressions of SYN, PSD-95, and GAP43 were found in the hippocampus of rats in MS+CUMS group. In conclusion, adult female rats that underwent MS and CUMS performed more critical depression-like and anxiety-like behaviors, and this process may be resulted from synaptic plasticity impairment.

scholarly journals Curcumin evokes antidepressant-like effects in mice by regulating miR-124/brain derived neurotrophic factor

2021 ◽  
Vol 18 (3) ◽  
pp. 603-609
Author(s):  
Yanhong Yi ◽  
Jing Li ◽  
Weian Chen
Keyword(s):  
Neurotrophic Factor ◽  
Preference Test ◽  
Brain Derived Neurotrophic Factor ◽  
Mild Stress ◽  
Dependent Manner ◽  
Immobility Time ◽  
Swimming Test ◽  
Sucrose Preference Test ◽  
Loss Of Appetite

Purpose: To investigate the effect and mechanism of curcumin on depression in mice Methods: Mice were subjected to chronic unpredictable mild stress (CUMS), and behavioural changes were evaluated by sucrose preference test (SPT) and forced swimming test (FST). CUMS-treated mice received curcumin at a concentration of 50, 100, or 200 mg/kg. The level of MiR-124 was measured by real-time polymerase chain reaction (RT-PCR). Brain-derived neurotrophic factor (BDNF) levels were evaluated by western blotting. Results: CUMS induced depressive behaviour in mice, with increase in miR-124 and decrease in BDNF. Curcumin inhibited miR-124 expression and promoted BDNF in a dose-dependent manner in CUMS-treated mice. Brain-derived neurotrophic factor was the direct target of miR-124, decreasing the transcription of BDNF, but this was reversed by curcumin in vitro. MicroRNA-124 overexpression aggravated CUMS-induced depressive symptoms including loss of appetite, less sucrose consumption, shorter swimming time, and longer immobility time (p < 0.001). The effects were attenuated by curcumin. Conclusion: Curcumin alleviates CUMS-induced depressive behaviour by regulating miR-124/BDNF, suggesting that curcumin may a viable treatment option for depression.

scholarly journals An Antagonistic Peptide of Gpr1 Ameliorates LPS-Induced Depression through the Hypothalamic-Pituitary-Ovarian Axis

Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 857
Author(s):  
Rongrong Li ◽  
Chiyuan Ma ◽  
Yue Xiong ◽  
Huashan Zhao ◽  
Yali Yang ◽  
...  
Keyword(s):  
Ovarian Function ◽  
Preference Test ◽  
Antidepressant Effect ◽  
Normal Female ◽  
Reproductive Axis ◽  
Immobility Time ◽  
Potential Therapeutic Application ◽  
Antagonistic Peptide ◽  
Sucrose Preference Test ◽  
G Protein Coupled

Depression affects the reproductive axis at the hypothalamus and pituitary levels, which has a significant impact on female fertility. It has been reported that G protein-coupled receptor 1 (Gpr1) mRNA is expressed in both the hypothalamus and ovaries. However, it is unclear whether there is a relationship between Gpr1 and depression, and its role in ovarian function is unknown. Here, the expression of Gpr1 was recorded in the hypothalamus of normal female mice, and co-localized with gonadotrophin-releasing hormone (GnRH) and corticotropin-releasing factor (CRF). We established a depression mouse model to evaluate the antidepressant effect of G5, an antagonistic peptide of Gpr1. The results show that an intraperitoneal injection of G5 improves depressant–like behaviors remarkably, including increased sucrose intake in the sucrose preference test and decreased immobility time in the forced swimming tests. Moreover, G5 treatment increased the release of reproductive hormone and the expression of ovarian gene caused by depression. Together, our findings reveal a link between depression and reproductive diseases through Gpr1 signaling, and suggest antagonistic peptide of Gpr1 as a potential therapeutic application for hormone-modulated depression in women.

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