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.

miR-124 antagonizes the antidepressant-like effects of standardized gypenosides in mice

2018 ◽  
Vol 32 (4) ◽  
pp. 458-468 ◽  
Author(s):  
Li-Tao Yi ◽  
Rong-Hao Mu ◽  
Shu-Qi Dong ◽  
Shuang-Shuang Wang ◽  
Cheng-Fu Li ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Neurotrophic Factor ◽  
Glucocorticoid Receptors ◽  
Brain Derived Neurotrophic Factor ◽  
Sucrose Preference ◽  
Mild Stress ◽  
Dependent Manner ◽  
Receptor Kinase ◽  
Immobility Time ◽  
Tyrosine Receptor Kinase

Our previous study demonstrated that gypenosides produced antidepressant-like effects in mice exposed to chronic mild stress in a brain-derived neurotrophic factor-dependent manner. However, whether other mechanisms are involved in the antidepressant-like effects of gypenosides is not clear. miR-124 is one of the most abundant microRNAs in the hippocampus, and its dysregulation is related to the pathophysiology of depression. The glucocorticoid receptor is dysfunctional in depression, and it is a direct target of miR-124. Therefore, the present study used corticosterone-induced mice as a model to evaluate the role of miR-124 on the antidepressant-like effects of gypenosides. miR-124 agomir was intracerebrally injected prior to administration of gypenosides and corticosterone injection. Sucrose preference and forced swimming tests were performed 21 days later. Proteins related to glucocorticoid receptors and brain-derived neurotrophic factor-tyrosine receptor kinase B signaling in the hippocampus were evaluated. Our results demonstrated that gypenosides reversed the chronic corticosterone injection-induced decreased sucrose preference and increased immobility time. In contrast, this effect was antagonized by miR-124 injection. In addition, gypenosides increased glucocorticoid receptor and tyrosine receptor kinase B expression in the hippocampus, which activated brain-derived neurotrophic factor signaling. miR-124 also blocked these effects. In conclusion, this study demonstrated that a reduction in miR-124 was required for the antidepressant-like effects of gypenosides induced by chronic corticosterone injection in mice.

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.

scholarly journals Impaired CNS Leptin Action Is Implicated in Depression Associated with Obesity

Endocrinology ◽  
2011 ◽  
Vol 152 (7) ◽  
pp. 2634-2643 ◽  
Author(s):  
Nobuko Yamada ◽  
Goro Katsuura ◽  
Yukari Ochi ◽  
Ken Ebihara ◽  
Toru Kusakabe ◽  
...  
Keyword(s):  
Neurotrophic Factor ◽  
High Fat Diet ◽  
Control Diet ◽  
Preference Test ◽  
Antidepressant Activity ◽  
Brain Derived Neurotrophic Factor ◽  
Epidemiological Studies ◽  
High Fat ◽  
Depressive Behavior ◽  
Sucrose Preference Test

Recent epidemiological studies indicate that obesity increases the incidence of depression. We examined the implication of leptin for obesity-associated depression. Leptin induced antidepressive behavior in normal mice in a forced swimming test (FST), and leptin-overexpressing transgenic mice with hyperleptinemia exhibited more antidepressive behavior in the FST than nontransgenic mice. In contrast, leptin-deficient ob/ob mice showed more severe depressive behavior in the FST than normal mice, and leptin administration substantially ameliorated this depressive behavior. Diet-induced obese (DIO) mice fed a high-fat diet showed more depressive behavior in the FST and in a sucrose preference test compared with mice fed a control diet (CD). In DIO mice, leptin induced neither antidepressive action nor increment of the number of c-Fos immunoreactive cells in the hippocampus. Diet substitution from high-fat diet to CD in DIO mice ameliorated the depressive behavior and restored leptin-induced antidepressive action. Brain-derived neurotrophic factor concentrations in the hippocampus were significantly lower in DIO mice than in CD mice. Leptin administration significantly increased hippocampal brain-derived neurotrophic factor concentrations in CD mice but not in DIO mice. The antidepressant activity of leptin in CD mice was significantly attenuated by treatment with K252a. These findings demonstrated that leptin induces an antidepressive state, and DIO mice, which exhibit severe depressive behavior, did not respond to leptin in both the FST and the biochemical changes in the hippocampus. Thus, depression associated with obesity is due, at least in part, to impaired leptin activity in the hippocampus.

Repeated ketamine administration redeems the time lag for citalopram's antidepressant-like effects

2015 ◽  
Vol 30 (4) ◽  
pp. 504-510 ◽  
Author(s):  
G.-F. Zhang ◽  
W.-X. Liu ◽  
L.-L. Qiu ◽  
J. Guo ◽  
X.-M. Wang ◽  
...  
Keyword(s):  
Remission Rate ◽  
Time Lag ◽  
Onset Time ◽  
Preference Test ◽  
Mild Stress ◽  
Once Daily ◽  
Treatment Regimens ◽  
Antidepressant Effects ◽  
Swimming Test ◽  
Sucrose Preference Test

AbstractCurrent available antidepressants exhibit low remission rate with a long response lag time. Growing evidence has demonstrated acute sub-anesthetic dose of ketamine exerts rapid, robust, and lasting antidepressant effects. However, a long term use of ketamine tends to elicit its adverse reactions. The present study aimed to investigate the antidepressant-like effects of intermittent and consecutive administrations of ketamine on chronic unpredictable mild stress (CUMS) rats, and to determine whether ketamine can redeem the time lag for treatment response of classic antidepressants. The behavioral responses were assessed by the sucrose preference test, forced swimming test, and open field test. In the first stage of experiments, all the four treatment regimens of ketamine (10 mg/kg ip, once daily for 3 or 7 consecutive days, or once every 7 or 3 days, in a total 21 days) showed robust antidepressant-like effects, with no significant influence on locomotor activity and stereotype behavior in the CUMS rats. The intermittent administration regimens produced longer antidepressant-like effects than the consecutive administration regimens and the administration every 7 days presented similar antidepressant-like effects with less administration times compared with the administration every 3 days. In the second stage of experiments, the combination of ketamine (10 mg/kg ip, once every 7 days) and citalopram (20 mg/kg po, once daily) for 21 days caused more rapid and sustained antidepressant-like effects than citalopram administered alone. In summary, repeated sub-anesthestic doses of ketamine can redeem the time lag for the antidepressant-like effects of citalopram, suggesting the combination of ketamine and classic antidepressants is a promising regimen for depression with quick onset time and stable and lasting effects.

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 Tetragonia tetragonioides Relieves Depressive-Like Behavior through the Restoration of Glial Loss in the Prefrontal Cortex

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Yujin Choi ◽  
Yunna Kim ◽  
Hwa-Young Lee ◽  
Seung-Hun Cho
Keyword(s):  
Prefrontal Cortex ◽  
Preference Test ◽  
Tail Suspension Test ◽  
Antidepressant Effect ◽  
Antidepressant Agent ◽  
Immobility Time ◽  
Swimming Test ◽  
Asian Pacific ◽  
Sucrose Preference Test ◽  
Tetragonia Tetragonioides

Tetragonia tetragonioides, which is a halophyte and grows widely in Asian-Pacific regions, has been used for the treatment of digestive disorders in traditional oriental medicine. This study examined the potential antidepressant effect of Tetragonia tetragonioides in an astroglial degeneration model of depression, which was established based on the postmortem study of depressive patients’ brain presenting diminished astrocytes in the prefrontal cortex. C57BL/6 male mice were exposed to glial ablation in the prefrontal cortex by the administration of the gliotoxin, L-alpha-aminoadipic acid (L-AAA) to induce depression. Tetragonia tetragonioides at doses of 100 mg/kg and 300 mg/kg, imipramine at a dose of 15 mg/kg, and distilled water were orally administrated to mice for 18 days. Behavioral tests including the open field test (OFT), sucrose preference test (SPT), forced swimming test (FST), and tail suspension test (TST) were carried out after 2 days of L-AAA injection. The expression levels of GFAP and NeuN in the prefrontal cortex were determined by immunohistochemistry. Mice subjected to glial ablation in the prefrontal cortex displayed decreased sucrose consumption in SPT and increased immobility time in FST and TST. Treatment with imipramine and Tetragonia tetragonioides remarkably ameliorated the behavioral despair induced by L-AAA. In addition, immunohistochemistry analysis showed that treatment with Tetragonia tetragonioides significantly restored the glial loss as indicated by the elevated GFAP expression level. These findings suggest that Tetragonia tetragonioides exerts an antidepressant effect through the restoration of glial loss under conditions of depression and can be a candidate for an antidepressant agent.

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 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 Sulfoquinovosyl oleoyl palmitoyl glycerol (SQDG) and hexane extract of Sargassum plagyophylum prevent depression induced by dexamethasone or stress in mice

2021 ◽  
Vol 10 (2) ◽  
pp. 262-268
Author(s):  
Afsaneh Yegdaneh ◽  
Azadeh Mesripour ◽  
Marjan Keyvani
Keyword(s):  
Preference Test ◽  
Hexane Extract ◽  
Sucrose Preference ◽  
Clinical Evaluations ◽  
Antidepressant Effects ◽  
Immobility Time ◽  
Swimming Test ◽  
Isolated Compound ◽  
Sucrose Preference Test ◽  
Palmitoyl Glycerol

Introduction: M Glucocorticoids and stress are a leading cause of depression by dysregulation of hypothalamic hypophyseal adrenal axis. Sargassum plagyophylum hexane extract (HxE) has proven antidepressant-like effects in mice. We aimed at evaluating HxE and sulfoquinovosyl oleoyl palmitoyl glycerol (SQDG) isolated compound antidepressant effects following dexamethasone (Dex) or water avoidance stress (WAS) induced depression in mice. Methods: The HxE was prepared and fractionated by different chromatography methods to isolate active compounds. Depression was induced in male mice by Dex single dose or by four days of WAS. After the locomotor test, depression was assessed by measuring the immobility time during the forced swimming test (FST) and sucrose preference test. Results: 6-Deoxy-6-sulpho-α-D-glucopyranosyl-1,2-O-diacyl-glycerol was isolated and elucidated from the seaweed. The manipulations did not cause important changes in animals’ locomotor activity. During FST, immobility time increased dramatically by Dex (193 ± 13 s vs control 109 ± 7 s) or WAS (189 ± 13 s vs sham 86 ± 14 s), that indicated depression. HxE 40 mg/kg reduced the immobility time when it was administered with Dex (110 ± 28 s, P < 0.01 vs Dex alone) or together with WAS (86 ± 11 s, P < 0.001 vs WAS). SQDG 40 mg/kg reduced the immobility time when co-administered with Dex (22 ± 9 s, P < 0.001 vs Dex alone) and when it was administered along with WAS (68 ± 16 s, P < 0.001 vs WAS). The results of the sucrose preference test were in line with FST results as sucrose preference below 65% was considered for anhedonia. Conclusion: SQDG and probably the steroid content in S. plagyophylum HxE prevented depression in mice; thus, they should be considered for further clinical evaluations.

Administration of cannabidiol and imipramine induces antidepressant-like effects in the forced swimming test and increases brain-derived neurotrophic factor levels in the rat amygdala

2011 ◽  
Vol 23 (5) ◽  
pp. 241-248 ◽  
Author(s):  
Gislaine Z. Réus ◽  
Roberto B. Stringari ◽  
Karine F. Ribeiro ◽  
Tatiana Luft ◽  
Helena M. Abelaira ◽  
...  
Keyword(s):  
Neurotrophic Factor ◽  
Forced Swimming Test ◽  
Cannabis Sativa ◽  
Field Tests ◽  
Brain Derived Neurotrophic Factor ◽  
Chemical Constituent ◽  
Forced Swimming ◽  
Antidepressant Effects ◽  
Immobility Time ◽  
Swimming Test

Réus GZ, Stringari RB, Ribeiro KF, Luft T, Abelaira HM, Fries GR, Aguiar BW, Kapczinski F, Hallak JE, Zuardi AW, Crippa JA, Quevedo J. Administration of cannabidiol and imipramine induces antidepressant-like effects in the forced swimming test and increases brain-derived neurotrophic factor levels in the rat amygdala.Objective: Cannabidiol is a chemical constituent from Cannabis sativa and it has multiple mechanisms of action, including antidepressant effects. The main objective of the present study was to evaluate behavioural and molecular effects induced by administration of cannabidiol and imipramine in rats.Methods: In the present study, rats were acutely or chronically treated for 14 days once a day with saline, cannabidiol (15, 30 and 60 mg/kg) or imipramine (30 mg/kg) and the animals behaviour was assessed in forced swimming and open-field tests. Afterwards, the prefrontal cortex, hippocampus and amygdala brain-derived neurotrophic factor (BDNF) levels were assessed by enzyme-linked immunosorbent sandwich assay.Results: We observed that both acute and chronic treatments with imipramine at the dose of 30 mg/kg and cannabidiol at the dose of 30 mg/kg reduced immobility time and increased swimming time; climbing time was increased only with imipramine at the dose of 30 mg/kg, without affecting locomotor activity. In addition, chronic treatment with cannabidiol at the dose of 15 mg/kg and imipramine at the dose of 30 mg/kg increased BDNF levels in the rat amygdala.Conclusion: In conclusion, our results indicate that cannabidiol has an antidepressant-like profile and could be a new pharmacological target for the treatment of major depression.

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