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Depression is a common psychiatric disorder characterized by low mood with complex pathophysiological mechanisms and poor effect of pharmacological treatment.The animals were placed in greater sensory, physical and/or social stimuli than those of the standard feeding environment, so that they can obtain positive plasticity and adaptability.Environmental enrichment(EE) is a common intervention to improve brain function in laboratory.A large number of studies have shown that EE had significant ameliorative effects on various animal models of depression, but the mechanisms have not been yet fully understood with outcome heterogeneity in ethology.There was no universally accepted and unified paradigm and standard for EE due to its multi-dimensionality and complexity.Therefore, it is necessary to improve the structural components and implementation steps of EE by integrating the existing data.Combined with recent studies on animal models of depression, this paper reviewed the anti-depression mechanism of EE from promoting hippocampal neurogenesis, reducing neuroinflammation, regulating neuroendocrine and affecting epigenetic modifications, in order to provide new ideas for mechanisms research and treatment of depression.As the rise of precision medicine and individualized medicine brings human growing interest in exploring the sources and mechanisms of inter-individual differences and intra-group effects of depression, it will be a challenge to translate EE to the human society in a rational way.
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@#Depression, a global disease with various pathogenic factors, is seriously affecting human physical and mental health. In Chinese traditional medical theory, the disease belongs to the category of "Yu Zheng". At present, on the one hand, adverse reactions to antidepressant western medicine are becoming more and more prominent. On the other hand, the study of their antidepressant active ingredients and compatibility mechanisms has become a difficult field in the traditional Chinese medicine compounds due to their complexity. The Chinese antidepressant herb-pairs has become a hot topic in the field of antidepressant research. Herb-pair is the core of traditional Chinese medicine compound. In addition, the compound itself is a herb-pair. The study of traditional Chinese antidepressant herb-pairs is more conducive to clarify the compatibility mechanism of herb interaction and the mechanism of antidepressants on the body.Therefore, this paper systematically expounds antidepressant herb-pairs from the study of material, pharmacokinetics and efficacy, which aims at providing theoretical support for the compatibility mechanism of antidepressant herb-pairs and the research of new antidepressant drugs.
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To investigate the effects of Shugan Hewei Decoction and its active substance fractions on behavior and neurotransmitter levels in hypothalamus of depression model rats,and preliminarily explore its possible mechanism. Male SD rats were randomly divided into blank control group,model group,fluoxetine( positive control) group,Shugan Hewei Decoction high and low dose groups,high and low dose groups of three different substance fractions. After 3 weeks' CUMS and social isolation to induce models,intragastrical administration lasted for 7 d. Behavioral experiments( sucrose consumption test,open-field test,and forced swimming test) were then performed to evaluate the depression status of rats. Several neurotransmitters in hypothalamus of rats were determined by LC-MS/MS method,including dapamine( DA),norepinephrine( NE),serotonin( 5-HT),5-indoleacetic acid( 5-HIAA),γ-aminobutyric acid( GABA),and glutamic acid( Glu). As compared with the blank control group,the sucrose consumption was reduced( P<0. 01); the total distance and the number of crossing the central area were also significantly reduced( P< 0. 01,P< 0. 01),while the resting time increased significantly( P<0. 01); the forced swimming time was significantly prolonged( P<0. 01); DA,5-HT,NE,5-HIAA and GABA levels in hypothalamus were significantly reduced( P < 0. 01),while Glue level was significantly increased( P < 0. 01) in model group. As compared with the model group,all the above indexes had changes in fluoxetine group,Shugan Hewei Decoction whole recipe groups,volatile oils group,polysaccharides group,and terpenoids group( P<0. 01 or P<0. 05). Shugan Hewei Decoction whole recipe and its active substance fractions can improve the behavior of depression model rats and may exert anti-depression effects by regulating the content of neurotransmitters in the hypothalamus.
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Animals , Male , Rats , Chromatography, Liquid , Depression , Drug Therapy , Drugs, Chinese Herbal , Pharmacology , Hypothalamus , Chemistry , Neurotransmitter Agents , Chemistry , Random Allocation , Rats, Sprague-Dawley , Tandem Mass SpectrometryABSTRACT
Objective To analyze the effect of Compound Chaigui Prescription on the changes of serum metabolites in rats with depression by 1H-NMR metabolomics. Methods Rats model established were modeled by chronic mild unpredictable stress (CUMS) procedure. Compound Chaigui Prescription and positive drugs (venlafaxine) were used as intervention drugs. Rat serum was analyzed by nuclear magnetic resonance (NMR) method. After data pretreatment, SIMCA-P 14.1 software was introduced for multivariate statistical analysis to verify the antidepressant efficacy of Compound Chaigui Prescription from the perspective of small molecule metabolites, and find potential disease biomarkers and drug efficacy markers. Results The CUMS depression rat model was successfully replicated. The metabolomics results showed that the levels of isoleucine, trimethylamine oxide, and creatine in the serum of CUMS-depressed rats were significantly higher than those of the model group. The levels of N-acetyl-glycoprotein, choline, and glucose were decreased with a significant difference (P < 0.05, 0.01). Conclusion The serum metabolite levels in CUMS model rats were significantly corrected after Compound Chaigui Prescription intervention. This study can provide reference for the study of antidepression mechanism of Compound Chaigui Prescription.
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Objective To investigate the effect of antidepressants on frontal lobe inflammatory factors in depressed model rats.Methods Thirty SD rats were randomly divided into 5 groups (n=6):contorl group(Cn),depression group (Dn),citalopram group (Dx),venlafaxine group (Dw) and reboxetine group (Dr).The open field test and sugar consumption test were performed to observe the depression behavior and the changes of FGF-1,TNF-α,IL-1 and CRP were measured in frontal lobe of rats by ELISA.Pearson linear correlation analysis was used to evaluate the correlation between behavioral score and inflammatory factors level in rats.Results (1)Compared with the Cn group,the scores of Dn,Dr,Dw,Dx group were decreased on Open field test and sugar consumption test (P＜0.05).Compared with the Dn group,the scores of the Dx,Dw,Dr group were increased in Open field test and sugar consumption test (P＜0.05).(2)Compared with Cn group,the levels of TNF-α,IL-1 and CRP increased in Dn group and FGF-1 level decreased (P＜0.01).Compared with Dn group,the levels of FGF-1 increased in Dx ((86.54±2.56) ng/L),Dw((79.82±4.89) ng/L)and Dr ((68.50 ± 3.61) ng/L) group,however,the levels of TNF-α decreased in Dx ((150.21±5.65) ng/L),Dw ((161.28±8.80) ng/L),Dr ((175.78±9.67) ng/L) group,and the level of IL-1 also decreased in Dx ((30.87±4.48) ng/L),Dw ((36.65±3.33) ng/L),Dr ((40.14±2.81)ng/L) group,and the levels of CRP also decreased in Dx ((374.88 ± 14.15) ng/L),Dw ((394.21 ± 17.03) ng/L),Dr ((414.34± 10.97)ng/L) (P＜0.01).(3)The behavioral score of each group was positively correlated with of FGF-1 and negatively correlated with TNF-a,IL-1 and CRP (P＜0.05).Conclusion Antidepressants can reduce the level of proinflammatory factors and increase the level of anti-inflammatory factors of frontal lobe in depression model rats,suggesting that antidepressants may play an antidepressant effect by regulating the concentration of inflammatory factors.
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Objective: To study the mechanism of Jiaotai Pill on inflammation and anti-inflammatory cytokines in mice with chronic unpredictable mild stress (CUMS) depression. Methods: Mice were treated with CUMS depression model, then the weight comparison, sugar test, opening experiment was conducted; The levels of IL-1β, IL-6 and TNF-α, IL-4, and IL-10 in the serum and hippocampus of rats were measured by enzyme-linked immunosorbent assay (ELISA), and rat hippocampal neuron morphology was observed by Nissl's staining. Results: Compared with the blank group, the consumption of sugar, the number of crosses and the number of vertical bars in the model group were significantly decreased; The levels of IL-1β, IL-6, TNF-α, and IL-4 in serum and hippocampus were significantly higher than those in the blank group, and IL-10 significantly reduced; Hippocampal neurons stratified unclear, arranged disorder, Nissie shallow staining or disappear. Compared with the model group, the consumption of sugar, the number of crosses and the number of vertical bars in Jiaotai Pill administration group were significantly increased; The levels of IL-1β, IL-6, and TNF-α in serum and hippocampus were significantly decreased, and the levels of IL-4 and IL-10 was significantly increased; Hippocampal neuronal stratification was more obvious, Nissl shallow staining. Conclusion: Jiaotai Pill can significantly improve the behavior of rat depression and hippocampal neuronal injury whose mechanism may be related to down-regulation of serum and hippocampus proinflammatory cytokines IL-1β, IL-6, TNF-α, up-regulation of anti-inflammatory cytokines IL-4 and IL-10.
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Objective To study the content of monoamine neurotransmitters and neurotrophic factor in the hippocampus, amygdala and prefrontal cortex in anxious depression rats, and explore the possible pathogenesis.Methods 60 SD rats were randomly divided into normal group, vehicle group, anxiety group, depression group, and anxious depression group, 12 rats in each group.Chronic restraint stress combined with corticosterone injection was used to establish anxiety and depression model, the modeling time was 21 d.After modeling, elevated plus maze test, open field test, and forced swimming test were used to evaluate the anxiety and depression-like behavior, HPLC-ECD was used to detect the content of 5-HT, NE, and DA in the hippocampus, amygdala, and prefrontal cortex of rats.Western-blotting was used to detect the expression of BDNF and NT-3 in rats.Results Rats in anxious depression model group were comparable to the anxiety group in time and frequency entering open arm time, and number of locomotor activity in open field, and it had a significant difference when compared with the control and depression groups (P<0.01 or P<0.05).Immobile time in anxious depression model rats was increased significantly when compared with the control and anxiety groups (P<0.01).Meanwhile, compared with the control group, 5-HT in hippocampus and 5-HT, NE in amygdala or prefrontal cortex were significantly decreased in the depressive rats with anxiety (P<0.01 or P<0.05).Moreover, the content of BDNF and NT-3 was significantly decreased in each brain regions compared with the control group (P<0.01 or P<0.05), and BDNF levels were obviously decreased compared with the anxiety group (P<0.05).Conclusions Rats of anxious depression have significant anxiety and depression-like behaviors.Its mechanism may be associated with the down-regulation of monoamine neurotransmitters and neurotrophic factors BDNF and NT-3 in hippocampus, amygdala, and prefrontal cortex region.
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OBJECTIVE:To investigate the effects and mechanism of total flavonoids from Armeniaca mume on depression in chronic stress depression model rats. METHODS:60 rats were randomly divided into normal saline group,model group,fluox-etine group(positive control,20 mg/kg)and total flavonoids from A. mume low-dose,medium-dose,high-dose groups(80,160, 240 mg/kg), 10 in each group. Except for normal saline group, the other groups adopted chronic unpredictable mild stress (CUMS)+solitary feeding condition to induce depression model. These groups were intragastrically administered,once a day,for 28 d. Changes of body mass and food intake,degree of preference for sugar were observed;forced swimming test and tail suspen-sion test were used to determine the time that rats did not move;open field test was used to determine the changes of residence time in central square,horizontal crossing lattice,standing times,modification times;tumor necrosis factor α(TNF-α),cortisol, interleukin 6 (IL-6),serotonin (5-HT) levels in serum after 24 h of last administration were determined. RESULTS:Compared with normal saline group,growth of body mass,food intake and sugar preference percentage in model group were decreased;the time that rats did not move was prolonged in forced swimming test and tail suspension test;residence time in central square was prolonged,while horizontal crossing lattice,standing times and modification times were decreased in open field test;serum levels of TNF-α,cortisol were increased,while IL-6,5-HT were decreased,with statistical significances (P<0.05 or P<0.01). Com-pared with model group,except that there were no obvious improvement in sugar preference percentage,the time that rats did not move in forced swimming test,modification times in open field test in total flavonoids from A. mume low-dose group and IL-6, 5-HT levels in serum in total flavonoids from A. mume low-dose,medium-dose groups,the above-mentioned indexes were obvious-ly improved in other groups (P<0.05 or P<0.01). CONCLUSIONS:Total flavonoids from A. mume can obviously improve the CUMS-induced depression in rats,and the mechanism may be related to inhibiting inflammation response,adjusting the hypothala-mus-pituitary-adrenal axis functions.
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Objective: To investigate the effects of Paeoniae Alba Radix extracts (PAREs) on 5-HT3R mediated ion channels in primarily cultured hippocampal neurons of rats with depression. Methods: An animal model of depression was successfully developed and evaluated in rats. PARE was used for drug intervention. Serum in each group was collected, inactivated and then added into the primary hippocampal neurons for 24 h. The protein expression levels of 5-HT3AR and 5-HT3BR in the neurons of each group were examined by Western blotting (WB). The 5-HT3R channel current was recorded by a whole-cell patch clamp. Results: Compared with normal rats, the rats with depression had significantly reduction in total distance of the open-field test (OFT) and sucrose preference ratio (P < 0.01). The hippocampal neurons treated with serum of depressive rats had significantly increased protein expression of 5-HT3AR and 5-HT3BR (P < 0.05) and current density value (P < 0.05) compared to those treated with normal rat serum. Compared with the depressive rats, the rats treated with PARE and fluoxetine had significantly increased OFT (P < 0.05) and sucrose preference ratio (P < 0.01). The primary hippocampal neurons cultured with serum from PARE and fluoxetine-treated rats had significantly reduction in protein expression of 5-HT3AR and 5-HT3BR (P < 0.05, 0.01, 0.001) and current density value (P < 0.01). Conclusion: PARE can reduce the 5-HT3R ion channel current density in the rats with depression. This may be its central mechanism in treating depression.
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OBJECTIVE:To provide basis and thinking for the development of medicines for treating depression. METHODS:Rats with adaptive feeding for 7 d were randomly divided into normal group,depression group and treatment group(citalopram hy-drobromide 1 mg/kg),8 in each group. Rats in depression group and treatment groups randomly received once low-density stimula-tion in a day [catching tail stimulation(1 min),frequent flashing stimulation(120 times/min,12 h),noise stimulation(4 h),ice water swimming stimulation(1 h),hot water stimulation(45 ℃,1 h),electric shocking foot(10 Hz,1 mA,each time interval of 100 ms,100 times),no food and no water(24 h)] for 21 d to reduce stress depression model. Body mass of rats in 0,7 d of adaptive feeding and 7,14,21 d of stress were respectively weighed,and horizontal activity and vertical activity frequencies in open field test were detected. After stress,rats were intragastrically administrated related medicines for 30 d,then 5-hydroxytrypta-mine (5-HT) and tryptophan hydroxylase (TPH) expressions in brain,liver,kidney tissues were determined. RESULTS:Com-pared with normal group,the increasing trend of body mass in depression group and treatment group slowed down from the 14 d of stress(P<0.05). The horizontal activity frequencies in depression group and treatment group in 14,21 d of stress slowed more ob-viously than the previous time point (P<0.05 or P<0.01);vertical activity frequencies in 21 d of stress slowed more obviously than the previous time point (P<0.05 or P<0.01). After 30 d of administration,horizontal activity and vertical activity frequen-cies in treatment group were increased more obviously than the previous time point (P<0.01). Compared with depression group,brain tissue of rats,indicating that TPH can be used as a target for depression treatment.
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Objective: To validate the antidepressant effect of herb pair of Bupleuri Radix and Paeoniae Alba Radix by observing its interference effect in the chronic unpredictable mild stress (CUMS) depression model of rats. Methods: After the interference of herb pair of Bupleuri Radix and Paeoniae Alba Radix in CUMS depression model of rats, those changes of rat body weight, sugar water consumption, and the opening activity behavior were observed. Results: After the interference of herb pair of Bupleuri Radix and Paeoniae Alba Radix in CUMS depression model of rats for two weeks, the test indexes of rat body weight, sugar water consumption, and the opening activity behavior were significantly increased in low-, mid-, and high-dose herb pair of Bupleuri Radix and Paeoniae Alba Radix groups. The effect of herb pair of Bupleuri Radix and Paeoniae Alba Radix on improving the behavior of rats with depression was proved. In addition, Bupleuri Radix and Paeoniae Alba Radix could also improve the level of individual indicators in a certain degree. Conclusion: Herb pair of Bupleuri Radix and Paeoniae Alba Radix has the obvious antidepressant effect on rats and the antidepressant effect of Bupleuri Radix and Paeoniae Alba Radix separately is lower than it.
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Objective To investigate the variation of middle cerebral arteries of rats in depression model by using 3D-TOF sequence on 3.0T MR.Methods Forty SD rats were randomly divided into control group and depressive group with 20 in each.Compared with control group,depressive group were handled according to the demand of rat depression model.Rats were scanned by 3.0T MR on 0th,4th,6th,8th week respectively.Using Mimics software,the variation of middle cerebral arteries were described and analysed.Results Compared with the control group,the middle cerebral arteries of depressive group rats changed along with the increase of time.On the 4th week,the diameter of the middle cerebral arteries of rats decreased significantly (the diameter of left middle cerebral arteries:control group (0.31 ±0.05) mm,depressive group (0.28±0.04) mm,t=2.76,P＜0.05 ; the diameter of right middle cerebral arteries:control group (0.30 ± 0.05) mm,depressive group (0.27± 0.03) mm,t =2.61,P＜ 0.05).On the 6th week,the length of the middle cerebral arteries of rats decreased significantly (the length of left middle cerebral arteries:control group (5.6± 0.77) mm,depressive group (4.9 ± 0.73) mm,t =2.84,P＜ 0.05 ; the length of right middle cerebral arteries:control group(5.5±0.76) mm,depressive group(4.8±0.72) mm,t=3.11,P ＜0.05).On the 8th week,the diameter and length of the middle cerebral arteries of rats decreased more significantly (the diameter of left middle cerebral arteries:control group (0.31 ±0.05) mm,depressive group (0.22±0.02) mm,t =5.50,P＜ 0.01 ; the diameter of right middle cerebral arteries:control group (0.30 ± 0.04) mm,depressive group (0.21 ±0.02) mm,t=5.57,P＜0.01 ; the length of left middle cerebral arteries:control group (5.6±0.78) mm,depressive group (4.3±0.70)mm,t=5.49,P＜0.01 ;the length of right middle cerebral arteries:control group (5.5 ± 0.79) mm,depressive group (4.2±0.71)mm,t=5.45,P＜0.01).Conclusion The variation of middle cerebral arteries of depressive rats reveals the relationship between brain vessels and depression in a certain extent.
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Objective To investigate the abnormity of superoxide dismutase (SOD), malondialdehyde (MDA) and cyclooxygenase-2 (COX-2) in colon of rats caused by depression.Methods The chronic stress-induced model of depression of wistar rats was produced . The experimental animals were randomly divided into model control and normal control in the study. The levels of SOD and MDA were assayed with ultraviolet spectrophotometry. The expression of COX-2 in colonic tissue was detected with immunohistochemistry.Results Enhanced colon inflammatory response and oxidative stress were observed in the chronic stress-induced depression model of rats, which manifested as the significant increase of MDA, as well as the expressions of COX-2 in the colon tissue, while the colonic SOD activity was significantly decreased compared with the normal control (MDA: 10.34±2.77 vs 2.55±0.70; COX-2: 53.26±8.16 vs 4.87±1.05; SOD:53.39±11.15 vs 84.45±22.31; P <0.01). Conclusion Depression can induce injuries on colon of rats, which was probably due to the abnormity of metabolism of oxygen free radical (OFR) and arachidonic acid.
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Objective:To observe the effect of liquiritin on body weight and behavior in depression model rats.Methods:Seventy-two male Sprague-Dawley(SD)rats were randomly assigned into normal control group,model group(stress+vehicle),fluoxetine group(stress+ fluoxetine)and three liquiritin groups(stress+liquiritin at different dose).The behavior of rats was detected by sucrose consumption test and forced swimming test.Results:The model rats showed significantly lower body weight(429?45/494?37,P
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OBJECTIVE:To explore the effects of bioactive compounds from entomogenous fungi(BCEF0083)on hip-pocampus neurons and mRNA expression of BDNF in chronic stress depression rat models.METHODS:The selected rats were randomly divided into control group,model group,moclobemide20mg/kg group,and BCEF0083100,50,25mg/kg groups.The change in hippocampus neuron numbers were observed by HE staining and mRNA expression of BDNF was detected with RT-PCR.RESULTS:BCEF0083could increase the neuron numbers and up-regulate the expression of BDNF mRNA in hippocampus.CONCLUSION:The antidepressant effect of BCEF0083in chronic stress depression rat models is probably re-lated to the increase in hippocampus neuron numbers and up-regulation of expression of BDNF mRNA in hippocampus.