Environmental enrichment ameliorates anxiety and depression-like behaviors in paternally stressed offspring mice through upregulation of hippocampal LASP1 / 西安交通大学学报(医学版)

【Objective】 To explore the role of environmental enrichment (EE) in paternal stress-induced anxiety and depression-like behaviors in offspring and its potential mechanisms. 【Methods】 Male C57BL/6 mice (F0) were treated with unpredictable chronic mild stress (UCMS) and subsequently mated with normal females to obtain F1 offspring mice. The standard environment (SE) and enriched environment (EE) were administered to F1-UCMS offspring mice during their early life (3-5 weeks of age). Anxiety-like behaviors were detected by open field test (OFT) and elevated plus-maze test (EPM); depression-like behaviors were detected via forced swimming test (FST) and sucrose preference test (SPT) at the age of 8 weeks. The expressions of LIM and SH3 domain protein 1 (LASP1) in the hippocampus of adult F1 offspring mice were detected by Real-time fluorescence quantitative PCR (RT-qPCR) and Western blotting. 【Results】 Compared to F1 offspring of normal paternal (F1-Nor), F1 offspring mice of the stressed paternal (F1-UCMS) showed significantly anxiety-like behavior with reduced percentage of time spent in the central region of OFT and in the open arm of EPM (P<0.05); mice from the F1-UCMS group showed a significantly increased percentage of immobility in FST and a reduced percentage of sugar consumption in SPT (P<0.01), which demonstrated significant depression-like behaviors. Compared to the SE group, mice in the EE group had an increased percentage of time spent in the central region of the OFT [males: (7.44±0.75)% vs. (14.93±1.74)%, P<0.01; females: (8.89±1.06)% vs. (15.10±1.82)%, P<0.05] and an increased percentage of time in the open arm of EPM [males: (8.09±1.05)% vs. (14.15±1.88)%, P<0.05; females: (9.13±1.14)% vs. (14.04±1.37)%, P<0.05]. This indicated that EE ameliorated anxiety-like behavior in F1-UCMS mice with paternal stress. Compared to the SE group, mice in the EE group had an decreased percentage of immobility in FST [males: (58.63±4.51)% vs. (42.15±3.81)%, P<0.05; females: (57.96±4.19)% vs. (43.25±4.22)%, P<0.05] and an increased percentage of sugar consumption in SPT [males: (50.38±3.47)% vs. (70.39±3.12)%, P<0.01; females: (52.42±2.84)% vs. (69.99±3.55)%, P<0.01]. This indicated that EE ameliorated depression-like behavior in F1-UCMS mice with paternal stress. Hippocampal LASP1 expression was reduced in SE group compared to F1-Nor group (males: P<0.01; females: P<0.05), while LASP1 was increased in EE group compared to SE group (P<0.05) detected by RT-qPCR and Western blotting. 【Conclusion】 EE ameliorates paternal stress-induced anxiety and depression-like behaviors in F1-UCMS mice, and the mechanism may be associated with increased hippocampal LASP1 expression in F1-UCMS mice.

Effect of salvianolic acid on behaviors and brain inflammatory factors in depression model rats / 中华行为医学与脑科学杂志

Objective:To investigate the effect of salvianolic acid on depressive behavior in depression model rats induced by chronic mild stress (CMS) and its mechanism.Methods:Fifty healthy male clean grade Sprague-Dawley(SD) rats were divided into five groups according to a random number table with 10 in each group: control group (nCMS+ Nal group), CMS+ normal saline group (CMS+ Nal group), CMS+ fluoxetine group (CMS+ Flu group), CMS+ salvia acid group (CMS+ Sal group), CMS+ fluoxetine+ Salvia acid group (CMS+ Flu+ Sal group). Except the control group, the rats in the other four groups were all received CMS modeling for 21 days. Twenty-one days after CMS modeling, rats were intraperitoneally injected with 0.9% normal saline (10 mg·kg -1·d -1), fluoxetine (20 mg·kg -1·d -1), salvia acid(40 mg·kg -1·d -1), fluoxetine(20 mg·kg -1·d -1)+ salvia acid(40 mg·kg -1·d -1)for 21 days. During the administration period, rats in the other four groups continued to receive CMS intervention for 21 days. Forced swimming test and sucrose preference test were conducted at baseline (day 0), after modeling (day 21) and after intervention (day 42) so as to evaluate depression like behavior. Then the rats were sacrificed and the hippocampus and prefrontal cortex were taken. The mRNA levels of Toll like receptor 4 (TLR4) and myeloid differentiation primary response 88 (MyD88) were detected by RT-qPCR. The cytokines including interleukin-1β(IL-1β), interleukin-2(IL-2), interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) were detected by Luminex technique.SPSS 21.0 was used for statistical analysis.Repeated measurement ANOVA was used for behavioral data analysis, one-way ANOVA was used for molecular index data analysis, and Spearman was used for correlation analysis. Results:The results of repeated measurement ANOVA showed that the interaction effects between group and time of body mass, sucrose preference, forced swimming immobility time were significant at baseline, after modeling and after intervention ( F=18.238, 6.921, 7.591, all P<0.05). After modeling, compared with nCMS+ Nal group, the rats in CMS+ Flu group, CMS+ Sal group, CMS+ Flu+ Sal group and CMS+ Nal group had lower body weight, lower sucrose preference rate and longer forced swimming immobility time (all P<0.05). After intervention, compared with CMS+ Nal group(body weight (350.15±41.65)g, sucrose preference(52.95±11.13)%, static time(91.40±15.22)s), the body weight((378.21±30.78)g, (385.12±43.19)g, (391.41±31.21)g, (402.33±18.67)g, all P<0.05) and sucrose preference((69.30±15.56)%, (68.12±10.99)%, (71.18±9.51)%, (75.47±11.55)%, all P<0.05) of CMS+ Flu group, CMS+ Sal group, CMS+ Flu+ Sal group and nCMS+ Nal group were all increased, while the forced swimming immobility time ((68.81±21.74)s, (66.10±25.51)s, (63.53±22.32)s, (71.21±21.41)s, all P<0.05) were shorter (all P<0.05). After intervention, among the body weight, sucrose preference and the immobility time of CMS+ Flu group、CMS+ Sal group and CMS+ Flu+ Sal group, there were no differences between each two groups(all P>0.05). After intervention, the levels of TLR4 mRNA and MyD88 mRNA in prefrontal cortex and hippocampus of CMS+ Flu group, CMS+ Sal group, CMS+ Flu+ Sal group and nCMS+ Nal group were all lower than those in CMS+ Nal group (all P<0.05). In prefrontal cortex, the levels of TLR4 mRNA (0.715±0.358) and MyD88 mRNA (0.739±0.233) in CMS+ Flu+ Sal group were lower than those in CMS+ Sal group (1.943±0.606, 1.815±0.897) (both P<0.05). The level of TLR4 mRNA in prefrontal cortex and hippocampus of rats were positively correlated with the level of MyD88 mRNA and TNF-α level and forced swimming immobility time and negatively correlated with sucrose preference rate (prefrontal cortex r=0.915, 0.041, 0.027, -0.178, all P<0.05; hippocampus r=0.810, 0.070, 0.011, -0.153, all P<0.05). Conclusion:The antidepressant effect of salvianolic acid is presumedly achieved by inhibiting the immunoinflammatory response mediated by the TLR4/Myd88 signaling pathway in CMS rats.

Ayahuasca prevents oxidative stress in a rat model of depression elicited by unpredictable chronic mild stress

ABSTRACT Background: Depression is a highly disabling common mental disorder and, due to its multifactorial nature, the development of effective therapies is challenging and of great relevance. Ayahuasca (AYA), an entheogenic traditional beverage, has emerged as an alternative for antidepressant treatment, however, AYA preclinical and clinical trials are still incipient. Objectives: This investigation aimed to evaluate some behavioral and biochemical effects of AYA subchronic administration in rats submitted to a model of depression elicited by unpredictable chronic mild stress (UCMS). Methods: 500 mg/kg of AYA was administered in adult male rats once a day for 15 days before submitting the animals to UCMS. Anhedonia-like and locomotion behavior, lipid peroxidation, antioxidant enzyme activities, and sulfhydryl/nitrite content were evaluated. Results: AYA intake failed to prevent anhedonia-like behavior. Locomotion was not altered by AYA consumption or by the experimental condition. UCMS increased TBARS and nitrites levels, decreased the levels of catalase in the cerebral cortex and of Sulfhydryl in the hippocampus. AYA treatment counteracted these biochemical alterations but did not display any alterations in non-stressed rats. Conclusions: Taken together, results indicate an adaptogenic antioxidant molecular mechanism of AYA in relation to depression induced by stress.

A comparative study on depression and anxiety of mice (Mus musculus) on a prebiotic-supplemented diet versus a standard diet during Unpredictable Chronic Mild Stress (UCMS)

@#<p style="text-align: justify;"><strong>Background.</strong> Anxiety and depression are becoming increasingly prevalent today and are often aggravated by day-to-day stresses. Because current management strategies are usually accompanied by unpleasant side effects, there is a need to look into alternative treatment regimens - such as prebiotics - that may provide equally effective anxiolytic and antidepressant effects.</p><p style="text-align: justify;"><strong>Objective.</strong> Therefore, the study aims to determine the effect of a combined fructooligosaccharide (FOS) and galactooligosaccharide (GOS) supplemented diet on anxiety and depression levels in mice subjected to Unpredictable Chronic Mild Stress (UCMS).</p><p style="text-align: justify;"><strong>Methods.</strong> Forty male BALB/C mice were subjected to UCMS under a pretest-posttest control group design where the treatment group received prebiotic supplementation throughout the study. Repeated measures ANOVA was run to evaluate between, within, and time interactions of the measured anxiety parameters using the light-dark box test, and depression parameter using the fur coat state assessment.</p><p style="text-align: justify;"><strong>Results.</strong> Results show that (1) the FOS + GOS treatment did not give the treatment group an advantage over the control group during UCMS, (2) both groups grew more anxious and depressed over time, and (3) the treatment group grew more anxious with time in relation to control in terms of the total time spent in the light side.</p><p style="text-align: justify;"><strong>Conclusion.</strong> These imply that the UCMS protocol was successful in inducing stress in mice, but the FOS + GOS regimen failed to provide anxiolytic and antidepressant effects on male BALB/C mice exposed to UCMS.</p>

Efeitos do Estresse Crônico Moderado sobre o Desempenho de Ratos Wistar em Tarefas de Aprendizagem / Effects of Chronic Mild Stress on Performance of Wistar Rats in Learning Tasks

As pesquisas sobre o efeito do estresse crônico moderado (CMS) sobre a aprendizagem de não humanos apresentam resultados contraditórios. Este estudo investigou os efeitos do CMS sobre o desempenho de ratos em duas tarefas de aprendizagem: uma discriminação visual simultânea e uma aprendizagem espacial em labirinto aquático. Oito ratos Wistar machos foram divididos em grupo experimental (GE, exposto ao CMS) e grupo controle (GC). Após exposição do GE ao protocolo de CMS por três semanas, ambos os grupos passaram por uma tarefa de discriminação visual e pela tarefa de aprendizagem espacial no labirinto aquático de Morris (MWM), além de testes de preferência por solução de sacarose. O GE continuou sendo exposto ao CMS durante a tarefa de discriminação visual. Os resultados sugerem que o CMS pode ter reduzido o ganho de peso e dificultado a aprendizagem de discriminação visual do GE, sem alterações na preferência por sacarose e no MWM. De acordo com os resultados do presente estudo e da literatura em geral, os efeitos do CMS sobre a aprendizagem podem depender de sua duração e da complexidade da tarefa.

Researches on the effect of chronic mild stress (CMS) on non-human learning present contradictory results. This study investigated the effects of CMS on rats' performance in two learning tasks: a simultaneous visual discrimination and a spatial learning task in a water maze. Eight Wistar rats were divided into experimental group (GE, exposed to CMS) and control group (GC). After the GE group had been submitted to the CMS protocol for three weeks, both groups were exposed to a visual discrimination task and spatial learning task in the Morris Water Maze (MWM), in addition to preference tests for a sucrose solution. GE continued to be exposed to CMS for visual discrimination task. Results suggested that CMS may reduce weight gain and make the visual discrimination learning more difficult for the GE, without changes on the sucrose preference and MWM. According to the results of the present study and the literature in general, the effects of CMS on learning may depend on the duration and complexity of the task.

Virus-Mediated Overexpression of ETS-1 in the Ventral Hippocampus Counteracts Depression-Like Behaviors in Rats / 神经科学通报·英文版

ETS-1 is a transcription factor that is a member of the E26 transformation-specific (ETS) family. Galanin receptor 2 (GalR2), a subtype of receptors of the neuropeptide galanin, has been shown to have an antidepressant-like effect after activation in rodents. Our previous study has shown that overexpression of ETS-1 increases the expression of GalR2 in PC12 phaeochromocytoma cells. However, whether ETS-1 has an antidepressant-like effect is still unclear. In this study, we found that chronic mild stress (CMS) decreased the expression of both ETS-1 and GalR2 in the ventral hippocampus of rats. Meanwhile, we demonstrated that overexpression of ETS-1 increased the expression of GalR2 in primary hippocampal neurons. Importantly, we showed that overexpression of ETS-1 in the ventral hippocampus counteracted the depression-like behaviors of CMS rats. Furthermore, we found that overexpression of ETS-1 increased the level of downstream phosphorylated extracellular signal-regulated protein kinases 1 and 2 (p-ERK1/2) of GalR2 in the ventral hippocampus of CMS rats. Taken together, our findings suggest that ETS-1 has an antidepressant-like effect in rats, which might be mediated by increasing the level of GalR2 and its downstream p-ERK1/2 in the ventral hippocampus.

Neuroprotective effects of estrogen on rat model of perimenopausal depression and possible mechanism / 国际药学研究杂志

Objective: To investigate the antidepressant roles of estrogen in the perimenopausal depression rat model and po- tential mechnisms. Methods: The perimenopausal depression rat model was performed by ovariectomized(OVX)rat following unpre- dictable chronic mild stress(UCMS). The rats were divided into 6 groups:the control group(CON),OVX group,model (OVX+UC- MS)group,estrogen(estradiol,E2)treatment group,escitalopram group(ESC),and OVX+E2 group. Open filed and sucrose prefer- ence tests were used to investigate depression-like behavior. Nissl staining was used to analyze neuron numbers in the dentate gyrus (DG)region of rat hippocampus,Levels of 5-HT,5-H1AA, norepinephrine(NE)and dopamine(DA)in the hippocampus were deter- mined by the HPLC method,while the levels of several markers associated with HPA axis were determined by ELISA. Results: OVX+ UCMS decreased the number of crosses and rearings in open field test and decreased sucrose preference in sucrose preference test in the perimenopausal depression rat model. E2 treatment could reverse the depression behavior. E2 treatment also reversed the de- creased neuron numbers of DG region in the rat hippocampus and decreased monamine transmitter and high hypothalamic-pituitary-ad- renal axis(HPA)activation. Conclusion: E2 plays antidepressant roles in perimenopausal depression rat model through protecting neuron,increasing monamine transmitter level and decreasing HPA axis activation.

Effects of Galanin Receptor 2 Agonist on Depression-like Behavior in Chronic Mild Stress Model Rats / 中国康复理论与实践

Objective To explore the effect of intracerebroventricular injection of AR-M1896, a galanin receptor 2 agonist, on depres-sion-like behavior in rat chronic mild stress (CMS) model. Methods 48 Sprague-Dawley rats were randomly assigned into control group, CMS group, CMS artificial cerebrospinal fluid (aCSF) group and CMS AR-M1896 group equally. The control group received no interven-tion, and the other groups were established chronic mild stress model. After six-week of stress, forced swim test and sucrose preference test were conducted to identify the CMS rats. AR-M1896 or aCSF was injected into the lateral ventricle of CMS AR-M1896 group and CMS aC-SF group, respectively. The immobility time and climbing time in the forced swim test were analysed, and the sucrose consumption percent-age in the sucrose preference test was measured. Results The immobility time decreased (F=11.998, P<0.01), climbing time increased (F=8.268, P<0.05), and the sucrose consumption percentage increased (F=10.352, P<0.01) in CMS AR-M1896 group, compared with CMS aC-SF group. Conclusion Intracerebroventricular administration of galanin receptor 2 agonist AR-M1896 is effective on depression in CMS model rats.

7,8-Dihydroxyflavone, a Tropomyosin-Kinase Related Receptor B Agonist, Produces Fast-Onset Antidepressant-Like Effects in Rats Exposed to Chronic Mild Stress

OBJECTIVE: Brain-derived neurotrophic factor (BDNF) and its specific receptor, tropomyosin-related kinase (TrkB), play important roles in treating depression. In this experiment, we examined whether 7,8-dihydroxyflavone, a novel potent TrkB agonist, could reverse the behavioral and biochemical abnormalities induced by the chronic mild stress (CMS) paradigm in rats. METHODS: SD rats were exposed to a battery of stressors for 56 days. 7,8-dihydroxyflavone (5 and 20 mg/kg) were administered intraperitoneally during the last 28 days of the CMS paradigm. Rats were tested in sucrose consumption test (SCT), forced-swimming test (FST) and elevated T-maze (ETM). Serum corticosterone levels and hippocampal BDNF levels of the rats were measured. RESULTS: Four-week CMS on the rats induced their depression-like behavior in SCT. The CMS-reduced sucrose consumption was reversed starting from 7 days after the 7,8-dihydroxyflavone (20 mg/kg) treatment and remained across the subsequent treatment regime. 7,8-dihydroxyflavone, when given at 5 mg/kg for 3 weeks, reduced the immobility time in the FST in the CMS-subjected rats. Additionally, the 4-week treatment with 7,8-dihydroxyflavone (20 mg/kg) attenuated the CMS-induced increase in anxiety-like behavior in the ETM. For the CMS-subjected rats, 7,8-dihydroxyflavone treatment dose-dependently reduced their serum corticosterone levels but increased their hippocampal BDNF levels only at 5 mg/kg. CONCLUSION: 7,8-dihydroxyflavone was beneficial for both depression and anxiety-like behaviors, and may exert fast-onset antidepressant effects. This provides a new insight into the pharmacological management of depression.

Effect of Chronic Stress on Cardiac Sympathetic Nerve Function and Susceptibility of Ventricular Arrhythmia in Experimental Rats / 中国循环杂志

Objective: To investigate the changes of cardiac sympathetic nerve function and susceptibility of ventricular arrhythmia at chronic stress condition in experimental rats. Methods: A total of 30 SD rats were randomly assigned into two groups: Control group, the rats were fed with normal condition and Chronic stress group, the rats were fed with unpredictable chronic stimulus program.n=15 in each group and all animals were treated for 4 weeks. The behavior of rats was assessed by open ifeld test and sucrose intake test, the susceptibility of ventricular arrhythmia was measured by Burst stimulus program under narcosis condition, and the sign of cardiac sympathetic nerve reconstruction, tyrosine hydroxylase content was examined by immunohistochemistry. Results: Compared with Control group, Chronic stress group had decreased ratio of sucrose favorite/open field test, P0.05. Immunohistochemistry presented that Chronic stress group had much higher tyrosine hydroxylase content (1397.8 ± 268.8) um2/mm2 than Control group (995 ± 232.3) um2/mm2,P Conclusion: Chronic stress may increase the susceptibility of ventricular arrhythmia in experimental rats, and the cardiac sympathetic nerve reconstruction might be an important mechanism.

The study on the expression of the p-CREB in a rat model of chronic mild stress.WANG Lingxiao, PENG / 中国神经精神疾病杂志

Objective To better understand the role of CREB signaling pathway in chronic mild stress (CMS), we investigated the alteration of CREB and p-CREB in CMS rats with and without fluoxetine hydrochloride. Methods Fifty adult male Sprague-Dawley rats were randomly divided into three groups:CMS group (26), fluoxtine group (12) and con-trol group (12). The rats in CMS group and fluoxtine group received 8 weeks of chronic mild stress. Rats in fluoxtine group were administered daily injections of fluoxetine 10mg/kg I.P. Sucrose preference tests and open-field test were car-ried out after the 8th week. Based on endpoint sucrose-intake, animals were further divided into 4 groups:CMS sensitive group, CMS resilient group, fluoxtine group and control group. Western blot was used to detect the expression levels of CREB and p-CREB in the hippocampus and prefrontal cortex. Results The sucrose consumption was significantly de-creased in CMS resilience group compared to sensitive group, control group and fluoxetine-intervention group (all P<0.05). Similarly, the numbers in total arm entries, percentage of entries into open arms and time spent in open arms was significantly lower in CMS resilience group compared to control group(all P<0.05), but not different compared to CMS sensitive group(all P<0.05). The p-CREB in the hippocampus was significantly lower in CMS sensitive rat compared to CMS resilience group, control group and fluoxetine-intervention group(all P<0.05), but CREB was not dfferent among the four groups(all P<0.05). Conclusions The elevated phosphorylation of CREB in the hippocampus and prefrontal cortex of resilience CMS rats may contribute to the mood alteration induced by stress.

Strain Differences in the Chronic Mild Stress Animal Model of Depression and Anxiety in Mice

Chronic mild stress (CMS) has been reported to induce an anhedonic-like state in mice that resembles some of the symptoms of human depression. In the present study, we used a chronic mild stress animal model of depression and anxiety to examine the responses of two strains of mice that have different behavioral responsiveness. An outbred ICR and an inbred C57BL/6 strain of mice were selected because they are widely used strains in behavioral tests. The results showed that the inbred C57BL/6 and outbred ICR mice were similarly responsive to CMS treatment in sucrose intake test (SIT) and open field test (OFT). However, the two strains showed quite different responses in forced swimming test (FST) and novelty-suppressed feeding (NSF) test after 3 weeks of CMS treatment. Only C57BL/6 mice displayed the depression- and anxiety-like behavioral effects in response to CMS treatment in FST and NSF test. Our results suggest that there are differences in responsiveness to CMS according to the different types of strain of mice and behavioral tests. Therefore, these results provide useful information for the selection of appropriate behavioral methods to test depression- and anxiety-like behaviors using CMS in ICR and C57BL/6 mice.

Antidepressive effects of petroleum ether extract from Ranae Oviductu and its possible mechanism / 中草药

Objective: To study the antidepressive effect of the petroleum ether extract from Ranae Oviductus (PERO) on chronic mild stress depressive rat model and its mechanism. Methods: The rats were divided into control, model, Fluoxetine (10 mg/kg, positive control), and different doses (30, 100, and 300 mg/kg) of PERO groups. The rats in PERO groups were administered once daily for 21 d, while the rats in the control and model groups were administered with equivalent normal saline. After 1 h for the rats in PERO and model groups and 0.5 h for the rats in Fluoxetine group of the last administration, the chronic unpredictable mild stress for 21 d was used to induce the depression in rats. The body weight was measured and the depressive-like behaviors were evaluated by the open-field test and sucrose preference test. Then the corticosterone level in the rat plasma was detected by enzyme-linked immunosorbent assay (ELISA) and the brain-derived neurotrophic factor (BDNF) protein levels in the hippocampus were measured by Western blotting analysis. Results: Compared with the control group, the body weight, sucrose preference, and motion distance in open-field test of rats were decreased, the corticosterone level in plasma was increased, and the BDNF level in hippocampus was decreased. Compared with the model group, PERO treatment alleviated the body weight decreasing, increased the sucrose preference and motion distance, reduced the corticosterone level in the plasma of rats, and increased the BDNF level in hippocampus of rats. Conclusion: The antidepressive effect of PERO is likely mediated by modulating the function of hypothalamic-pituitary-adrenal axis and increasing the expression of BDNF in brain tissues.

Effect of long-term chronic mild stress on depression-like behavior and the expression of heat shock protein 70 in rats / 中华行为医学与脑科学杂志

Objective To explore the effect of long-term chronic mild stress on depression-like behaviors and the expression of heat shock protein 70(HSP70) in rats.Methods The standard SD rats were divided into two groups as following:one group (n =6) was treated with chronic mild stress for 3 weeks,and another group (n =5) was treated with chronic mild stress for 6 weeks.Depression-like behaviors of rats was observed by sucrose consumption test and open field test before and after chronic mild stress.And Western Blot,RT-PCR and immunohistochemistry were utilized to detect the HSP70 expression in the hippocampus and frontal lobes of rats after chronic mild stress.Results The sucrose favoritism in sucrose consumption test,the scores of crossing and the time for rats' retention in the center grid of open field test in long-term group were higher than those in short term group(P＜ 0.05).HSP70 expression in the hippocampus and frontal lobes of long-term group (0.81 ± 0.08,0.85 ± 0.08)detected by Western Blot and immunohistochemistry was higher that of short-term group (0.60 ± 0.06,0.85 ±0.07).HSP70 expression in the hippocampus of long-term group (0.90 ± 0.05,1.37 ± 0.38)detected by RT-PCR was higher that of short-term group(0.78 ± 0.04,1.08 ± 0.14) (P ＜ 0.05).Conclusion After long-term chronic mild stress,the depression-like behaviors decrease,and at the same time HSP70 mRNA and protein increase.

Effects of Chronic Mild Stress in Female Bax Inhibitor-1-Gene Knockout Mice

OBJECTIVE: The anti-apoptotic protein Bax inhibitor-1 (BI-1) is a regulator of apoptosis linked to endoplasmic reticulum (ER) stress, and BI-1-/- mice exhibit increased sensitivity to tissue damage. The purpose of this study was to investigate the role of BI-1 in the pathogenesis of chronic mild stress (CMS)-induced depression-like behaviors in BI-1-/- mice. METHODS: We delivered CMS for 2 or 6 weeks in BI-1-knockout and wild-type mice. Control groups of BI-1-knockout and wild-type mice were left undisturbed. The measured parameters were sucrose consumption at weeks 1, 2, 3, 4, 5, and 6, spontaneous locomotion, and a forced swimming test (FST) at weeks 2 and 6. RESULTS: Significant decreases in sucrose consumption and increases in immobility time in the FST were observed in both stress groups compared with the non-stress groups. Interestingly, at week 2, but not at week 6, BI-1-/--stress mice showed less sucrose intake and greater immobility time than did BI-1+/+-stress mice. CONCLUSION: These results suggest that BI-1 may play role in protecting against the depressogenic effects of CMS in the short term, but not in the long term. Further study is required to deepen understanding of the role of BI-1 in protecting against depression.

Behavioural and neurochemical evaluation of Perment® an herbal formulation in chronic unpredictable mild stress induced depressive model.

Perment®, a polyherbal Ayurvedic formulation that contains equal parts of Clitoria ternatea Linn., Withania somnifera Dun., Asparagus racemosus Linn., Bacopa monniera Linn., is used clinically as mood elevators. The aim of the present study was to explore the behavioural effects and to understand possible mode of action of Perment® in stress induced depressive model. Chronic unpredictable mild stress (CUMS) was used to induce depression in rats. Open field exploratory behaviour, elevated plus maze, social interaction and behavioural despair tests were used to assess behaviour. Using standard protocols plasma noradrenaline, serotonin, corticosterone and brain/adrenal corticosterone levels were measured to support the behavioural effects of Perment®. Exposure to CUMS for 21 days caused anxiety and depression in rats, as indicated by significant decrease in locomotor activity in the open field exploratory behaviour test and increased immobility period in the behavioural despair test. Perment® predominantly exhibited antidepressant action than anxiolytic activity. Further Perment® increased the plasma noradrenaline and serotonin levels in stressed rats. No significant alteration in the brain corticosterone level in stressed rats was observed with Perment® treatment. However the adrenal corticosterone level is decreased with Perment®. It can be concluded that the Perment® formulation exhibited synergistic activity, has a significant antidepressant and anxiolytic activity, which may be mediated through adrenergic and serotonergic system activation. Currently the formulation is clinically used as anxiolytic but the present results suggest that the formulation can also be indicated in patients affected with depression.

Anti-depressant Mechanisms of Wuling Jun Powder by Gene Microarray Analysis / 中国康复理论与实践

@#ObjectiveTo explore the possible mechanisms of Wuling Jun Power by the DNA microarray technique.MethodsAn experimental depression model was established by exposing the mouse to a chronic mild stress procedure. The total RNA was extracted reverse-transcripted and hybrided to the mouse 1-2 cDNA microarray (Clontech). The difference of expression profiles between control model, Wuling Jun powder and fluoxetine-treated groups were analyzed by the Image 2-1 Software.Results130 genes were significantly altered in stress group compared with the control groups. Among them, 116 genes were up-regulated and 14 genes were down-regulated. Meanwhile, 85 genes significantly changed in the Wuling Jun powder treated group with 34 genes up-regulated and 51 genes down-regulated compared with the model groups. For the Fluoxetine-treated group, 133 genes significantly changed with 35 genes up-regulated and 98 genes down-regulated compared with the model groups. These genes were associated with many aspects of life including receptor activity, protein kinases, inflammatory factors, transferrin, neurogenesis and so on.ConclusionMultiple genes were affected by the stress exposure. Altered changes of some genes were normalized by Wuling Jun powder and Fluoxetine treatment. In general, the mechanisms of Wuling Jun powder and Fluoxetine are similar, but also with minor difference.

Antidepressant-like activity of tetramethylpyrazine measured by acute and chronic experimental methods in rat model of depression / 中华行为医学与脑科学杂志

Objective To study the potential antidepressive-like effect of tetramethylpyrazine (TMP). Methods Forced-swimming and chronic mild stress (CMS) tests were performed to assess the antidepressant-like activity of TMP. Male Sprague-Dawley (SD) strain rats were divided into six matched groups (n= 13 or 14 in each group) based on their sucrose consumption:control, CMS, CMS + fluoxetine, and CMS + TMP groups. The rats except control were housed separately in different rooms, and the rat model of depression was established by exposing to an unpredictable sequence of stressors for 28 days; the rats in CMS + fluoxetine were exposed to CMS and received administration of FLU (2.0 mg· kg-1·d-1 ,ig) for 28 days; the rats in CMS + TMP groups were exposed to CMS and received administration of TMP (10,20,40 mg·kg-1·d-1 ,ig) , respectively, for 28 days. The rats in control group were given ordinary daily care and received ig administration of normal saline simultaneously. The body weight, food intake and fluid consumption were measured, and the behaviors were examined by open field during the duration of the stress procedure, and forced-swimming test was performed 1 day after last unpredictable stressor. Results Acute administration of TMP markedly decreased the duration of immobility during forced-swimming test((89.0 ±37.0)s vs (117.1 ±32. 1)s, P<0.05) . Chronic administration of TMP partially countered the effects of CMS on consumption of sucrose solution and locomotion and exploration behavior, and potently shortened the immobility time during forced-swimming test following CMS in rats. The results showed that long-term administration of TMP partially reversed the effects of CMS on the body weight gain,the consumption of sucrose solution,the squares crossing in open field test and the immobility time during forced-swimming test in rats ((91.9 ±31.5) vs (124.4±27.0)s,P<0.05).Conclusion TMP shows obvious antidepressant-like activity.

Effect of Ningshen Ling and dehydroepiandrosterone on the cognitive function in mice subjected to chronic mild stress / 中国康复理论与实践

@#ObjectiveTo investigate the alteration of behavior,such as spontaneous movement,spatial memory ability and cholinergic M receptors in the brain of mice subjected to chronic mild stress (CMS). And to determine whether Ningshen Ling (NSL)and dehydroepiandrosterone(DHEA)could reverse the cognitive impairment in this model.MethodsForty mice were divided into four groups: control group,CMS group,CMS+NSL(p.o.5g·kg-1·d-1) group and CMS+DHEA (i.p.5 mg·kg-1·d-1) group. Morris water maze procedure was used to determine the spatial memory ability. M receptor binding activity was measured with radioactivity assay by3 H-QNB.ResultsAfter 3 weeks CMS,the mice exerted a decrease in spontaneous movement test,and the latency in Morris water maze was obviously prolonged. Treating CMS mice with NSL and DHEA for 1 weeks could improve the spontaneous movement and latency declined. Whereas the3 H-QNB binding ability to M receptor showed a significantly decrease in cerebral cortex and hippocampus of CMS mice (P<0.05),the decreased ability of M receptor binding was reversed by NSL treatment in hippocampus(P<0.05).ConclusionNSL and DHEA can alleviate the stress response and reversed cognitive impairment induced by CMS,and it may be concerned with the central cholinergic M receptors activity.

Antidepressant Effects of Ethaverine, a Calcium Channel Antagonist, in Animal Models of Depression / 신경정신의학

OBJECTIVES: This pre-clinical study was performed to assess the effects of ethaverine in the two kinds of behavioral models of depression in rats. METHODS: We observed the changes of the immobility time in the forced swimming test and the quantity of sucrose consumed in the chronic mild stress model, using ethaverine(20mg/kg) alone, imipramine(20mg/kg) alone, or ethaverine and imipramine concomitantly. RESULTS: In the forced swimming test, both single treatment and chronic treatment(for 7 days) with imipramine or ethaverine significantly reduced the immobility time, and concomitant chronic treatment with ethaverine potentiated the effect of imipramine. In the chronic mild stress model, both imipramine and ethaverine reversed the decreased sucrose consumption induced by 3-week stress and concomitantly treated ethaverine potentiated the effect of imipramine in the early phase of treatment. CONCLUSIONS: The data suggest that ethaverine can be used alone or concomitantly with other anti-depressants in the clinical situation.