Background: Depression is a typical psychosomatic disease. Shuganheweitang (SGHWT) is a clinical formula that effectively treats depression. However, the potential mechanism used by SGHWT to ameliorate depression-like...Background: Depression is a typical psychosomatic disease. Shuganheweitang (SGHWT) is a clinical formula that effectively treats depression. However, the potential mechanism used by SGHWT to ameliorate depression-like behaviors is still unclear. This study investigated the effects of SGHWT on metabolic change in the liver and hypothalamus with signaling pathways involved in chronic unpredictable mild stress (CUMS)-induced depression in rats to explore the mechanism of the anti-depressive effect. Methods: A total of 52 rats were used to create a model of depression by CUMS combined with solitary rearing for 6 weeks. Open field test (OFT), sucrose preference test (SPT), forced swim test (FST), and body weight (BW) were performed to analyze the pharmacodynamic effects of SGHWT. H&E staining, Nissl staining, immunofluorescence, immunohistochemistry, and western blot were used to evaluate the mechanism of action. Untargeted metabolomics techniques by ultra-performance liquid chromatography-quantitative time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) were used to analyze all the metabolic differences in the liver and hypothalamus. Results: SGHWT improved CUMS-induced depression-like behaviors in vivo. SGHWT reduced hepatic c-Fos protein expression and increased hypothalamic c-Fos protein expression. Moreover, p-PI3K, p-AKT473, p-AKT308, and p-mTOR protein expressions were significantly downregulated in the liver and hypothalamus of CUMS rats. Notably, these alterations were reversed by the SGHWT administration. Furthermore, the metabolomic analysis identified 15 and 5 key differential SPT-associated metabolites in the liver and hypothalamus, respectively. Conclusion: This study suggests that SGHWT ameliorates chronic unpredictable mild stress-induced depression-like behaviors, by the involvement of amino acids, glycerophospholipids, energy metabolism, and the PI3K/AKT/mTOR pathway. Highlights: 1) Shuganheweitang was derived from the TCM herbal formula Sinisan. 2) SGHWT treatment reverses depression-like behaviors in CUMS-induced rats. 3) The mechanism of SGHWT on depression by the liver and hypothalamus metabolomics. 4) SGHWT regulates amino acids, glycerophospholipids, and energy metabolism. 5) SGHWT exerts antidepressant effects through the PI3K/AKT/mTOR pathway.展开更多
The depression-like behavior phenotype,neurogenesis in the dentate gyrus and miR-124 expression in the hippocampus are the focus of current research on the pathogenesis of depression and antidepressant therapy.The pre...The depression-like behavior phenotype,neurogenesis in the dentate gyrus and miR-124 expression in the hippocampus are the focus of current research on the pathogenesis of depression and antidepressant therapy.The present study aimed to clarify the dynamic changes of depression-like behavior,dentate gyrus neurogenesis and hippocampal miR-124 expression during depression induced by chronic stress to reveal pathological features at different stages of depression and to further provide insight into depression treatment.Chronic unpredictable mild stress depression models were established by exposing Sprague-Dawley rats to various mild stressors,including white noise,thermal swimming,stroboscopic illumination,soiled cages,pairing with three other stressed animals,cold swimming,tail pinch,restraint and water and food deprivation.Chronic unpredictable mild stress model rats underwent dynamic observation from 1 to 8 weeks and were compared with a control group(normal feeding without any stressors).To observe changes in the depression-like behavior phenotype during chronic unpredictable mild stress-induced depression,a sucrose preference test was used to evaluate the degree of anhedonia.An open-field test was used to evaluate locomotor activity and anxiety status.Compared with the control group,chronic unpredictable mild stress rats lost weight but did not have a depression-like behavioral phenotype at 1-4 weeks.Chronic unpredictable mild stress rats presented decreased sucrose preference and locomotor activity at 5-8 weeks.In addition,chronic unpredictable mild stress rats did not have significant anxiety-like behavior during 1-8 weeks of modeling.To observe neurogenesis dysfunctions and changes in neuronal number in the dentate gyrus during chronic unpredictable mild stress-induced depression,markers(DCX and DCX/BrdU)of neural proliferation and differentiation and the neuronal marker NeuN were assessed by immunofluorescence.Compared with the control group,neurogenesis and the neuronal number in the dentate gyrus did not change from 2 to 6 weeks;however,neural proliferation and differentiation in the dentate gyrus decreased,and the number of neurons decreased until the eighth week in the chronic unpredictable mild stress group.Real-time quantitative reverse transcription polymerase chain reaction assays and fluorescence in situ hybridization were used to measure the expression of hippocampal miR-124 during chronic unpredictable mild stress-induced depression.The results showed that the expression of hippocampal miR-124 was unchanged during the first 4 weeks but increased from 5 to 6 weeks and decreased from 7 to 8 weeks compared with the control group.These findings indicate that during chronic unpredictable mild stress-induced depression,the behavioral phenotype,miR-124 expression in the hippocampus,neurogenesis in the dentate gyrus and neuronal numbers showed dynamic changes,which suggested that various pathological changes occur at different stages of depression.All experimental procedures and protocols were approved by the Experimental Animal Ethics Committee of Guangzhou University of Chinese Medicine of China in March 2015.展开更多
Background:The chronic unpredictable mild stress(CUMS)model has long been considered the best model for exploring the pathophysiological mechanisms underlying depression.However,there are no widely recognised standard...Background:The chronic unpredictable mild stress(CUMS)model has long been considered the best model for exploring the pathophysiological mechanisms underlying depression.However,there are no widely recognised standards for strategies for modeling and for behavioral testing.The present study aimed to optimize the protocols for food deprivation and the sucrose preference test(SPT)for the CUMS model.Methods:We first evaluated the effects of different long periods of food deprivation on the body weight of Sprague Dawley(SD)rats by testing food deprivation for 24 hours(8:00-8:00^+),food deprivation for 12 hours during the daytime(8:00-20:00)and food deprivation for 12 hours at night(20:00-8:00^+).Next,we established a SD rat CUMS model with 15 different stimulations,and used body weight measurement,SPT,forced swim test(FST),open field test(OFT)and Morris water maze(MWM)test to verify the success of the modeling.In the SPT,consumption of sucrose and pure water within 1 and 12 hours was measured.Results:Twelve hours of food deprivation during the daytime(8:00-20:00)had no effect on body weight,while 12 hours of food deprivation at night(20:00-8:00^+)and 24 hours of food deprivation(8:00-8:00^+)significantly reduced the mean body weight of the SD rats.When SPT was used to verify the successful establishment of the CUMS rat model,sucrose consumption measured within 12 hours was less variable than that measured within 1 hour.Conclusions:Twelve hours of food deprivation in the daytime(8:00-20:00)may be considered a mild stimulus for the establishment of a CUMS rat model.Measuring sucrose consumption over 12 hours is recommended for SPT.展开更多
In recent years, more attention has been paid to the role of the glutamate transporter 1 (GLT-1, EAAT2) in major depressive disorder (MDD). However, experimental data on brain GLT-1 levels are, to some extent, inc...In recent years, more attention has been paid to the role of the glutamate transporter 1 (GLT-1, EAAT2) in major depressive disorder (MDD). However, experimental data on brain GLT-1 levels are, to some extent, inconsistent in human postmortem and animal studies, These discrepancies imply that the role of GLT-1 in the pathophysiology of MDD and the action of antidepressants remain obscure. This work was designed to study the impact of chronic unpredictable stress (CUS) for 2 ses- sions per day for 35 days and four weeks of fluoxetine (FLX) on depressive-like behaviors in rats, as well as the concomitant expression of the GLT-1 protein in the hippocampus. Behavioral changes were assessed by the sucrose preference and open field tests. GLT-1 levels were detected by immunohisto- chemistry and Western blot analysis. Our study demonstrated that the animals exposed to CUS showed depressive-like behaviors and exhibited a significant decrease in GLT-1 expression in the hippocampus. Chronic FLX treatment reversed the behavioral deficits and the CUS-induced decrease in GLT-1 levels. Taken together, our results support the reduction of GLT-1 in human postmortem studies in MDD and suggest that GLT-1 may be involved in the antidepressant activity of FLX. Our studies further support the notion that GLT-1 is an attractive candidate molecule associated with the fundamental processes of MDD and may be a potential, and novel pharmacological target for the treatment of MDD.展开更多
The impact of various vitamin D3(VD3)doses(1.0,2.5,or 5 mg/kg,s.c.)in mitigating the negative consequences of chronic unpredictable mild stress(CUMS)was investigated.Adult female rats with long-term estrogen deficienc...The impact of various vitamin D3(VD3)doses(1.0,2.5,or 5 mg/kg,s.c.)in mitigating the negative consequences of chronic unpredictable mild stress(CUMS)was investigated.Adult female rats with long-term estrogen deficiency were assessed using the sucrose preference test(SPT),the elevated plus-maze(EPM),the light/dark test(LDT),and the open-field test(OFT)to measure anhedonia-like and anxiety-like behavior.The corticosterone(CS)and adrenocorticotrophic hormone(ACTH)concentrations in blood serum and the brain-derived neurotrophic factor(BDNF)expression in the hippocampus of long-term ovariectomized(OVX)rats were measured by ELISA kits and/or western blotting.Treatment with VD3(5.0 mg/kg),similarly to fluoxetine(10.0 mg/kg),significantly reduced the anhedonia profile in the SPT and anxiety-like behavior in the EPM and LDT,and CS and ACTH levels in blood serum.It also elevated BDNF levels in the hippocampus of long-term OVX/CUMS compared to OVX/CUMS/solvent rats.Thus,these findings suggest that VD3(5.0 mg/kg)administration might attenuate the anxiety-like profile in long-term OVX adult rats subjected to the CUMS.This might occur via activation of the BDNF signaling pathway in the hippocampus and via restoration of CS and ACTH levels in blood serum.展开更多
The ability of an organism to adapt to aversive stressful situations or life challenging circumstances is very crucial to its state of health and survival. However, breakdown in adaptation due to persistent uncontroll...The ability of an organism to adapt to aversive stressful situations or life challenging circumstances is very crucial to its state of health and survival. However, breakdown in adaptation due to persistent uncontrollable stress, leads to impairment of bodily functions and onset of a variety of pathological disorders especially memory decline. This study was designed to evaluate the effect of Jobelyn®(JB), a potent antioxidant sorghum-based food supplement on unpredictable chronic mild stress (UCMS)-induced memory impairment in mice. Male Swiss mice were given JB (5 - 50 mg/kg, p.o) 30 min prior to exposure to UCMS for 14 consecutive days before testing for memory. Thereafter, the serum corticosterone level was estimated by using ELISA kits. The levels of malondialdehyde (MDA) and glutathione (GSH) as well as acetylcholinesterase activity were estimated in the brain homogenate using spectrophotometer. Histology of the brain tissues and estimation of the populations of viable neurons in the hippocampal region were done after staining with hematoxyline and eosin. Our results showed that JB reversed memory impairment and suppressed corticosterone concentrations induced by UCMS. Moreover, JB reduced oxidative stress in the brain of UCMS-mice as shown by decreased MDA levels and elevated GSH concentrations. It also decreased brain acetylcholinesterase activity when compared with chronic stress group (p < 0.05). Furthermore, JB (5 - 10 mg/kg, p.o) offered significant protection against UCMS-induced degeneration and death of neuronal cells of the cornu ammonis 3 (CA3) of the hippocampal region of the brain indicating neuroprotection. Taken together, these findings suggest that JB attenuates memory deficits induced by UCMS in mice and may be useful therapeutically for stress-related cognitive dysfunctions. The reduction in the levels of serum corticosterone, antioxidation, neuroprotection and inhibition of cholinesterase enzyme might be contributing significantly to the positive effect of JB on memory in mice exposed to unpredictable chronic mild stress.展开更多
Background:Depression is becoming increasingly prevalent around the world,imposing a substantial burden on individuals,families,as well as society.Quercetin is known to be highly effective in treating depression.Howev...Background:Depression is becoming increasingly prevalent around the world,imposing a substantial burden on individuals,families,as well as society.Quercetin is known to be highly effective in treating depression.However,additional research is needed to dissect the mechanisms of its anti-depressive effects.Methods:For this study,Sprague-Dawley(SD)rats were randomized into the control,model,quercetin,or fluoxetine group.The latter three groups were exposed to chronic unpredictable mild stress(CUMS)for 42 d.The first two groups received saline solution daily via oral gavage.Meanwhile,the quercetin group was orally administered a quercetin suspension(52.08 mg/kg)every day,while the fluoxetine group was orally administered a fluoxetine solution(2.08 mg/kg).Here,fluoxetine served as the positive control drug to compare the therapeutic effects of quercetin.The experimental period was 6 weeks.Depressive behaviors in rats were assessed through various physiological and behavioral measures.Additionally,pathological changes in hippocampal tissues were examined using Nissl staining.Serum cytokines were detected using an enzymelinked immunosorbent assay(ELISA),and immunohistochemistry was employed to quantify the levels and integral optical density(IOD)values of ionized calcium binding adaptor molecule-1(Iba-1)expression in the brain.Real-time fluorescence quantitative PCR(RT-qPCR)was utilized to evaluate the mRNA levels of inflammatory indicators as well as toll-like receptor 4(TLR4),and nuclear factor-κappa B P65(NF-κB P65)in hippocampus.Western blot(WB)technique was employed to observe the protein levels of TLR4,NF-κB P65,and phospho-NF-κB P65(p-NF-κB P65).Results:After 42 d of exposure to CUMS,rats exhibited a slow increase in body weight,a reduction in food intake,an abnormal preference for sugar water,and aberrant open-field behaviors.Pathological analysis revealed the disintegration,rupture,interruption,and disorganization of hippocampal neuronal cells after CUMS exposure,along with a decrease in Nissl bodies in the CA1 region.This was accompanied by the elevated expression of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6)in the serum and the upregulation of IL-1β,IL-6,and TNF-αmRNA expression in the hippocampus.Increases in Iba-1-positive cells and the IOD values of Iba-1 were detected in hippocampal microglia.Furthermore,TLR4 and NF-κB P65 mRNA and protein levels were upregulated in hippocampal tissues.Quercetin,an antidepressant,could alleviate depression-like symptoms in rats and downregulate inflammatory factors associated with the TLR4/NF-κB signaling pathway in hippocampal microglia,and its therapeutic effect was comparable to fluoxetine.Conclusion:In rat models of CUMS,quercetin may act as an antidepressant by inhibiting inflammation in hippocampal microglia via TLR4/NF-κB signaling pathway.These results offer experimental and theoretical support for applying quercetin in the clinical management of depression.展开更多
A CPG control mechanism is proposed for hopping motion control of biped robot in unpredictable environment. Based on analysis of robot motion and biological observation of animal's control mechanism, the motion contr...A CPG control mechanism is proposed for hopping motion control of biped robot in unpredictable environment. Based on analysis of robot motion and biological observation of animal's control mechanism, the motion control task is divided into two simple parts: motion sequence control and output force control. Inspired by a two-level CPG model, a two-level CPG control mechanism is constructed to coordinate the drivers of robot joint, while various feedback information are introduced into the control mechanism. Interneurons within the control mechanism are modeled to generate motion rhythm and pattern promptly for motion sequence control; motoneurons are modeled to control output forces of joint drivers in real time according to feedbacks. The control system can perceive changes caused by unknown perturbations and environment changes according to feedback information, and adapt to unpredictable environment by adjusting outputs of neurons. The control mechanism is applied to a biped hopping robot in unpredictable environment on simulation platform, and stable adaptive motions are obtained.展开更多
Objective:To investigate the antidepressant-like effects of Chaihu Shugan Powder(CSP,柴胡疏肝散)and to explore its underlying mechanisms.Methods:Thirty-two Sprague-Dawley rats were randomly divided into control(CON),c...Objective:To investigate the antidepressant-like effects of Chaihu Shugan Powder(CSP,柴胡疏肝散)and to explore its underlying mechanisms.Methods:Thirty-two Sprague-Dawley rats were randomly divided into control(CON),chronic unpredictable mild stress(CUMS),fluoxetine(FLU),and CSP groups,8 rats in each group.All of the rats except for those in the control group were subjected to 3 consecutive weeks of CUMS to establish the depression model.The open field test(OFT),forced swimming test(FST),and sucrose preference test were used to assess the anti-anxiety and antidepressant effects of CSP.Terminal deoxynucleotidyl transferase(Td T)d UTP nick-end labeling was used to determine the apoptosis rate in the hippocampal tissues.The m RNA and protein levels of glucose-regulated protein(GRP)78,spliced X-box-binding protein(XBP)-1,CCAAT/enhancerbinding protein homologous protein(CHOP),caspase-12,and c-Jun N-terminal kinase(JNK)in the hippocampus of rats were evaluated by real-time PCR and Western blot analysis,respectively.Results:Administration of CSP alleviated anxiety and depression-like behavior in CUMS rats,as revealed by enhanced time and distance in the center of the OFT(P<0.05),an increased preference for sucrose,and longer swimming time and shorter immobility time during the FST(all P<0.05).In addition,CSP treatment significantly reduced the rate of apoptosis in rat hippocampal neurons(P<0.05).The m RNA and protein expression levels of GRP78,spliced XBP-1,and CHOP were down-regulated along with the expression of caspase-12 and cleaved caspase-12 proteins(all P<0.05),whereas total and phosphorylated JNK1 protein levels did not differ significantly between control and CSP-treated rats.Conclusion:CSP can improve depression-like behavior in rats exposed to CUMS,possibly by suppressing CHOP and caspase-12 mediated apoptosis in the rat hippocampus.展开更多
Background Up to now there have been no satisfactory drugs to treat psychiatric disorders, and now bioactive compound from entomagenous fungi (BCEF0083) is a new type of bioactive compound from entomopathogenic fungi....Background Up to now there have been no satisfactory drugs to treat psychiatric disorders, and now bioactive compound from entomagenous fungi (BCEF0083) is a new type of bioactive compound from entomopathogenic fungi. Our previous investigations have shown that BCEF has an inhibition effect on monoamine oxidase. So, BCEF may be a latent antidepressant. This study aimed at observing the antidepressant effects and its mechanism of BCEF in the chronic unpredictable stress models in mice. Methods The antidepressant effects of BCEF were examined on the chronic unpredictable stress models in mice. Sixty mice were randomly divided to six groups. Animals were housed and isolated except saline group. Mice were exposed to different stressors per day randomly from day 1 to day 21. Body weight were weighed on day 1,day 10 and on day 21 during the 21-day stress procedure. Awarding response was detected by using method of calculating the 24-hour consumption of saccharum water. Step through test was used to evaluate the behavioral response. AVP contents in plasma were also detected by using radioimmunoassays. Results Chronic unpredictable stress resulted in a significant decrease of the body weight and could apparently cause escape behavior disturbance and gradual reduction of sensitivity to reward in animal models. Drug treatment (BCEF 25, 50, 100 mg/kg) could significantly ameliorate the decreased body weight and effectively reverse the escape behavior disturbance. The gradual reduction of sensitivity to reward, the anhedonic state, was also effectively reversed by BCEF. BCEF (50, 100 mg/kg) could also effectively restore the AVP content in the plasma.Conclusions This evidence suggests that BCEF can effectively inhibit the depression behavior and show strong antidepressant effect. BCEF can effectively restore the plasma AVP release and this may be an important mechanism of its antidepressant effect.展开更多
Aims Seed dormancy and the soil seed bank are crucial to plant regeneration strategy,especially in semiarid ecosystems with unpredictable precipi-tation.the aim of this study was to investigate how seed dormancy is co...Aims Seed dormancy and the soil seed bank are crucial to plant regeneration strategy,especially in semiarid ecosystems with unpredictable precipi-tation.the aim of this study was to investigate how seed dormancy is controlled by environmental factors and how it is correlated with the soil seed bank and regeneration of the perennial legume Oxytropis race-mosa,a dominant perennial herb in Mu Us Sandland of semiarid China.Methods Germination and imbibition experiments on fresh intact and scarified seeds of O.racemosa were used to identify physical dormancy(PY)in seeds of this species.Soil seed bank dynamics,timing of seedling emer-gence and the fate of buried seeds in the natural habitat were investigated.Important Findings PY was broken by mechanical scarification or wet heat/ice water cycles but not solely by dry heat or wet heat treatment.the soil seed bank exhibited seasonal changes in the number of seeds,which was highest in September and lowest in July.Seeds buried at different sand depths gradually lost dormancy;20-42%of the seeds remained dormant after 20 months of burial.Dormancy break occurs grad-ually throughout the year.Our results indicate that O.racemosa exhibits hardcoatedness heterogeneity that spreads germination of a seed cohort between seasons and years in the semiarid environ-ment,where the amount of precipitation during the growing season is highly variable.展开更多
With the support by the National Natural Science Foundation,agroup of international researchers led by Duan HaoHong(段昊泓),Li Jun(李隽)at Tsinghua University,and Edman Tsang and Dermot O’Hare at University of Oxford...With the support by the National Natural Science Foundation,agroup of international researchers led by Duan HaoHong(段昊泓),Li Jun(李隽)at Tsinghua University,and Edman Tsang and Dermot O’Hare at University of Oxford discovered a novel catalytic promoter role of molecular nitrogen(N2)in biomass transformation,which was published in Nature Catalysis(2019,2:1078—1087).展开更多
The spleen is critical for immunity.It is the largest immune organ and immune center in the peripheral system.While the relationship between behavior and immunity has been demonstrated in physiology and diseases,the r...The spleen is critical for immunity.It is the largest immune organ and immune center in the peripheral system.While the relationship between behavior and immunity has been demonstrated in physiology and diseases,the role of the spleen in behavior is not clear.To investigate the effects of the spleen on behaviors,we performed a refined splenectomy procedure on C57BL/6J mice and performed an open field test,circadian rhythm test,elevated plus maze,sucrose preference test,and Barnes maze test.Splenectomy did not induce changes in general locomotion,circadian rhythms,learning and memory,or depression/anxiety-related behaviors.To further investigate the effects of spleen on stress susceptibility,we established mouse models of depression through chronic unpredictable mild stress.The behavioral performances of mice subjected to splenectomy showed no differences from control animals.These findings suggest that splenectomy does not cause changes in baseline behavioral performance in mice.展开更多
The plasma optical boundary reconstruction technique based on Hommen's theory is promising for future tokamaks with high parameters. In this work, we conduct detailed analysis and simulation verification to estima...The plasma optical boundary reconstruction technique based on Hommen's theory is promising for future tokamaks with high parameters. In this work, we conduct detailed analysis and simulation verification to estimate the ‘logic loophole' of this technique. The finite-width effect and unpredictable errors reduce the technique's reliability, which leads to this loophole. Based on imaging theory, the photos of a virtual camera are simulated by integrating the assumed luminous intensity of plasma. Based on Hommen's theory, the plasma optical boundary is reconstructed from the photos. Comparing the reconstructed boundary with the one assumed, the logic loophole and its two effects are quantitatively estimated. The finite-width effect is related to the equivalent thickness of the luminous layer, which is generally about 2-4 cm but sometimes larger. The level of unpredictable errors is around 0.65 cm. The technique based on Hommen's theory is generally reliable, but finite-width effect and unpredictable errors have to be taken into consideration in some scenarios. The parameters of HL-2M are applied in this work.展开更多
Objective Patients with chronic ulcerative colitis(UC)often have mental symptoms such as depression and anxiety,and stress can lead to gastrointestinal diseases.However,the correlation between mental stress and UC is ...Objective Patients with chronic ulcerative colitis(UC)often have mental symptoms such as depression and anxiety,and stress can lead to gastrointestinal diseases.However,the correlation between mental stress and UC is unclear.In this paper,chronic unpredictable mild stress(CUMS)was utilized to evaluate the involvement of mental factors in the pathogenesis of UC.Methods The CUMS model was used to evaluate the direct/indirect involvement of mental factors in the pathogenesis of UC.The behavior was evaluated by the open field,forced swimming,and tail suspension tests.Body weight,the disease activity index(DAI)score,colon length,and HE staining of colon tissue were used to evaluate the action of CUMS and fluoxetine.Results The results showed that weight loss and the DAI score increased in CUMS mice,but they had no meaningful effect on colon length and morphological structure of colon tissue.However,CUMS aggravated dextran sulfate sodium(DSS)-induced colon length shortening and colon morphological structure damage.Fluoxetine significantly improved the DAI score,shortened colon length,and damaged morphology and structure of the colons induced by CUMS combined with DSS in mice.Fluoxetine also decreased the level of IL-6 in the serum and the TNF-αand IFN-γlevels of colon tissue.Fluoxetine simultaneously improved behavioral abnormalities induced by CUMS combined with DSS in mice.Conclusion CUMS aggravated the UC symptoms induced by DSS,and fluoxetine could improve the UC symptoms due to its improvement in the inflammatory level and behavioral abnormalities.展开更多
Objective:To explore the effects of CUMS combined with CRS on mouse hippocampal glial cells and synaptic plasticity-related proteins. Methods: Forty mice were randomly divided into normal group (n=20) and model group ...Objective:To explore the effects of CUMS combined with CRS on mouse hippocampal glial cells and synaptic plasticity-related proteins. Methods: Forty mice were randomly divided into normal group (n=20) and model group (n=20). The model group used CUMS combined with CRS to prepare a mouse model of depression for 7 weeks. The behavioral evaluation of the mice at 3 weeks and 7 weeks after modeling was performed by sugar water preference test, open field test and tail suspension test. After the experiment, the samples were collected, and the content of TNF-a in the hippocampus of mice was detected by enzyme-linked immunosorbent assay. Immunohistochemical method was used to detect the Iba-1 and GFAP MOD values of mouse hippocampal CA1 area, CA3 area and DG area. Western blot was used to detect the protein expression of Iba-1, GFAP, SYN1 and PSD-95 in the hippocampus. fluorescence quantitative PCR method was used to detect the expression of SYN1, PSD-95 mRNA in hippocampus. Results: At the 3rd week after modeling, the body weight, sugar water preference rate, total distance moved, number of standing uprights, and stay time in the central area of the mice in the model group were all lower than those in the normal group (P<0.05), and the tail suspension immobility time was longer than that in the normal group (P<0.01). After 7 weeks of modeling, the body weight, sugar water preference rate, total distance moved, number of erection times, central area residence time, and average movement speed of the mice in the model group were lower than those in the normal group (P< 0.05), the tail suspension immobility time was longer than that in the normal group (P<0.01). The contents of TNF-a in the hippocampus were higher than those in the normal group (P<0.05). The GFAP MOD value and the relative expression of GFAP protein in hippocampal CA1, CA3 and DG regions were significantly lower than those in the normal group (P<0.05). The Iba-1 MOD value and the relative expression of Iba-1 protein in hippocampal CA1, CA3 and DG regions were significantly higher than those in the normal group (P<0.05). The relative expression of SYN1 and PSD-95 protein and the relative expression of SYN1 and PSD-95 mRNA in the hippocampus were significantly lower than those in the normal group (P<0.05). Conclusion: After 3 weeks of CUMS and CRS modeling, the depression-like behavior of mice appeared, and the depression of mice was more obvious after 7 weeks of modeling. The depression mouse model made by CUMS combined with CRS method may be related to increased hippocampal inflammation, excessive activation of microglia, decreased number of astrocytes and decreased synaptic plasticity.展开更多
Digital twin is an essential enabling technology for 6G connected vehicles.Through highfidelity mobility simulation,digital twin is expected to make accurate prediction about the vehicle trajectory,and then support in...Digital twin is an essential enabling technology for 6G connected vehicles.Through highfidelity mobility simulation,digital twin is expected to make accurate prediction about the vehicle trajectory,and then support intelligent applications such as safety monitoring and self-driving for connected vehicles.However,it is observed that even if a digital twin model is perfectly derived,it might still fail to predict the trajectory due to tiny measurement noise or delay in the initial vehicle locations.This paper aims at investigating the sources of unpredictability of digital twin.Take the car-following behaviors in connected vehicles for case study.The theoretical analysis and experimental results indicate that the predictability of digital twin naturally depends on its system complexity.Once a system enters a complex pattern,its longterm states are unpredictable.Furthermore,our study discloses that the complexity is determined,on the one hand,by the intrinsic factors of the target physical system such as the driver’s response sensitivity and delay,and on the other hand,by the crucial parameters of the digital twin system such as the sampling interval and twining latency.展开更多
Post-stroke depression is associated with reduced expression of brain-derived neurotrophic factor (BDNF). In this study, we evaluated whether BDNF overexpression affects depression-like behavior in a rat model of po...Post-stroke depression is associated with reduced expression of brain-derived neurotrophic factor (BDNF). In this study, we evaluated whether BDNF overexpression affects depression-like behavior in a rat model of post-stroke depression. The middle cerebral artery was occluded to produce a model of focal cerebral ischemia. These rats were then subjected to isolation-housing combined with chronic unpredictable mild stress to generate a model of post-stroke depression. A BDNF gene lentiviral vector was injected into the hippocampus. At 7 days after injection, western blot assay and real-time quantitative PCR revealed that BDNF expression in the hippo- campus was increased in depressive rats injected with BDNF lentivirus compared with depressive rats injected with control vector. Furthermore, sucrose solution consumption was higher, and horizontal and vertical movement scores were increased in the open field test in these rats as well. These findings suggest that BDNF overexpression in the hippocampus of post-stroke depressive rats alleviates depression-like behaviors.展开更多
Shuganjieyu capsule has been approved for clinical treatment by the State Food and Drug Ad-ministration of China since 2008. In the clinic, Shuganjieyu capsule is often used to treat mild to moderate depression. In th...Shuganjieyu capsule has been approved for clinical treatment by the State Food and Drug Ad-ministration of China since 2008. In the clinic, Shuganjieyu capsule is often used to treat mild to moderate depression. In the rat model of depression established in this study, Shuganjieyu capsule was administered intragastrically daily before stress. Behavioral results conifrmed that depressive symptoms lessened after treatment with high-dose (150 mg/kg) Shuganjieyu capsule. Immunohistochemistry results showed that high-dose Shuganjieyu capsule signiifcantly increased phosphorylation levels of phosphorylation cyclic adenosine monophosphate response element binding protein and brain-derived neurotrophic factor expression in the medial prefrontal cortex and hippocampal CA3 area. Overall, our results suggest that in rats, Shuganjieyu capsule effec-tively reverses depressive-like behaviors by increasing expression levels of neurotrophic factors in the brain.展开更多
Adult BALB/c mice, individually housed, were stimulated with nine different stressors, arranged randomly, for 4 continuous weeks to generate an animal model of chronic stress. In chronically stressed mice, spontaneous...Adult BALB/c mice, individually housed, were stimulated with nine different stressors, arranged randomly, for 4 continuous weeks to generate an animal model of chronic stress. In chronically stressed mice, spontaneous locomotor activity was significantly decreased, escape latency in the Morris water maze test was prolonged, serum levels of total thyrotropin and total triiodothyronine were significantly decreased, and dopamine and norepinephrine content in the pallium, hippocampus and hypothalamus were significantly reduced. All of these changes were suppressed, to varying degrees, by L-tyrosine supplementation. These findings indicate that the neuroendocrine network plays an important role in chronic stress, and that L-tyrosine supplementation has therapeutic effects.展开更多
文摘Background: Depression is a typical psychosomatic disease. Shuganheweitang (SGHWT) is a clinical formula that effectively treats depression. However, the potential mechanism used by SGHWT to ameliorate depression-like behaviors is still unclear. This study investigated the effects of SGHWT on metabolic change in the liver and hypothalamus with signaling pathways involved in chronic unpredictable mild stress (CUMS)-induced depression in rats to explore the mechanism of the anti-depressive effect. Methods: A total of 52 rats were used to create a model of depression by CUMS combined with solitary rearing for 6 weeks. Open field test (OFT), sucrose preference test (SPT), forced swim test (FST), and body weight (BW) were performed to analyze the pharmacodynamic effects of SGHWT. H&E staining, Nissl staining, immunofluorescence, immunohistochemistry, and western blot were used to evaluate the mechanism of action. Untargeted metabolomics techniques by ultra-performance liquid chromatography-quantitative time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) were used to analyze all the metabolic differences in the liver and hypothalamus. Results: SGHWT improved CUMS-induced depression-like behaviors in vivo. SGHWT reduced hepatic c-Fos protein expression and increased hypothalamic c-Fos protein expression. Moreover, p-PI3K, p-AKT473, p-AKT308, and p-mTOR protein expressions were significantly downregulated in the liver and hypothalamus of CUMS rats. Notably, these alterations were reversed by the SGHWT administration. Furthermore, the metabolomic analysis identified 15 and 5 key differential SPT-associated metabolites in the liver and hypothalamus, respectively. Conclusion: This study suggests that SGHWT ameliorates chronic unpredictable mild stress-induced depression-like behaviors, by the involvement of amino acids, glycerophospholipids, energy metabolism, and the PI3K/AKT/mTOR pathway. Highlights: 1) Shuganheweitang was derived from the TCM herbal formula Sinisan. 2) SGHWT treatment reverses depression-like behaviors in CUMS-induced rats. 3) The mechanism of SGHWT on depression by the liver and hypothalamus metabolomics. 4) SGHWT regulates amino acids, glycerophospholipids, and energy metabolism. 5) SGHWT exerts antidepressant effects through the PI3K/AKT/mTOR pathway.
基金supported by the National Natural Science Foundation of China,No.81573858(to LLW)the Natural Science Foundation of Guangdong Province of China,No.2016A030313648(to CY)the Major Basic Research Project of Educational Commission of Guangdong Province of China,No.2017KZDXM020(to CY)
文摘The depression-like behavior phenotype,neurogenesis in the dentate gyrus and miR-124 expression in the hippocampus are the focus of current research on the pathogenesis of depression and antidepressant therapy.The present study aimed to clarify the dynamic changes of depression-like behavior,dentate gyrus neurogenesis and hippocampal miR-124 expression during depression induced by chronic stress to reveal pathological features at different stages of depression and to further provide insight into depression treatment.Chronic unpredictable mild stress depression models were established by exposing Sprague-Dawley rats to various mild stressors,including white noise,thermal swimming,stroboscopic illumination,soiled cages,pairing with three other stressed animals,cold swimming,tail pinch,restraint and water and food deprivation.Chronic unpredictable mild stress model rats underwent dynamic observation from 1 to 8 weeks and were compared with a control group(normal feeding without any stressors).To observe changes in the depression-like behavior phenotype during chronic unpredictable mild stress-induced depression,a sucrose preference test was used to evaluate the degree of anhedonia.An open-field test was used to evaluate locomotor activity and anxiety status.Compared with the control group,chronic unpredictable mild stress rats lost weight but did not have a depression-like behavioral phenotype at 1-4 weeks.Chronic unpredictable mild stress rats presented decreased sucrose preference and locomotor activity at 5-8 weeks.In addition,chronic unpredictable mild stress rats did not have significant anxiety-like behavior during 1-8 weeks of modeling.To observe neurogenesis dysfunctions and changes in neuronal number in the dentate gyrus during chronic unpredictable mild stress-induced depression,markers(DCX and DCX/BrdU)of neural proliferation and differentiation and the neuronal marker NeuN were assessed by immunofluorescence.Compared with the control group,neurogenesis and the neuronal number in the dentate gyrus did not change from 2 to 6 weeks;however,neural proliferation and differentiation in the dentate gyrus decreased,and the number of neurons decreased until the eighth week in the chronic unpredictable mild stress group.Real-time quantitative reverse transcription polymerase chain reaction assays and fluorescence in situ hybridization were used to measure the expression of hippocampal miR-124 during chronic unpredictable mild stress-induced depression.The results showed that the expression of hippocampal miR-124 was unchanged during the first 4 weeks but increased from 5 to 6 weeks and decreased from 7 to 8 weeks compared with the control group.These findings indicate that during chronic unpredictable mild stress-induced depression,the behavioral phenotype,miR-124 expression in the hippocampus,neurogenesis in the dentate gyrus and neuronal numbers showed dynamic changes,which suggested that various pathological changes occur at different stages of depression.All experimental procedures and protocols were approved by the Experimental Animal Ethics Committee of Guangzhou University of Chinese Medicine of China in March 2015.
基金This work was supported by Social livelihood projects of Chongqing Science and Technology Bureau(cstc2017shms-zdyfX0048,csts2017shmsA00007).
文摘Background:The chronic unpredictable mild stress(CUMS)model has long been considered the best model for exploring the pathophysiological mechanisms underlying depression.However,there are no widely recognised standards for strategies for modeling and for behavioral testing.The present study aimed to optimize the protocols for food deprivation and the sucrose preference test(SPT)for the CUMS model.Methods:We first evaluated the effects of different long periods of food deprivation on the body weight of Sprague Dawley(SD)rats by testing food deprivation for 24 hours(8:00-8:00^+),food deprivation for 12 hours during the daytime(8:00-20:00)and food deprivation for 12 hours at night(20:00-8:00^+).Next,we established a SD rat CUMS model with 15 different stimulations,and used body weight measurement,SPT,forced swim test(FST),open field test(OFT)and Morris water maze(MWM)test to verify the success of the modeling.In the SPT,consumption of sucrose and pure water within 1 and 12 hours was measured.Results:Twelve hours of food deprivation during the daytime(8:00-20:00)had no effect on body weight,while 12 hours of food deprivation at night(20:00-8:00^+)and 24 hours of food deprivation(8:00-8:00^+)significantly reduced the mean body weight of the SD rats.When SPT was used to verify the successful establishment of the CUMS rat model,sucrose consumption measured within 12 hours was less variable than that measured within 1 hour.Conclusions:Twelve hours of food deprivation in the daytime(8:00-20:00)may be considered a mild stimulus for the establishment of a CUMS rat model.Measuring sucrose consumption over 12 hours is recommended for SPT.
基金supported by the Key Technology Research of Major Mental Illness Prevention and Treatment for the Barriers to the Recognition and Prevention of Depression and Anxiety in the General Hospital,China(No.2012BAI01B05)
文摘In recent years, more attention has been paid to the role of the glutamate transporter 1 (GLT-1, EAAT2) in major depressive disorder (MDD). However, experimental data on brain GLT-1 levels are, to some extent, inconsistent in human postmortem and animal studies, These discrepancies imply that the role of GLT-1 in the pathophysiology of MDD and the action of antidepressants remain obscure. This work was designed to study the impact of chronic unpredictable stress (CUS) for 2 ses- sions per day for 35 days and four weeks of fluoxetine (FLX) on depressive-like behaviors in rats, as well as the concomitant expression of the GLT-1 protein in the hippocampus. Behavioral changes were assessed by the sucrose preference and open field tests. GLT-1 levels were detected by immunohisto- chemistry and Western blot analysis. Our study demonstrated that the animals exposed to CUS showed depressive-like behaviors and exhibited a significant decrease in GLT-1 expression in the hippocampus. Chronic FLX treatment reversed the behavioral deficits and the CUS-induced decrease in GLT-1 levels. Taken together, our results support the reduction of GLT-1 in human postmortem studies in MDD and suggest that GLT-1 may be involved in the antidepressant activity of FLX. Our studies further support the notion that GLT-1 is an attractive candidate molecule associated with the fundamental processes of MDD and may be a potential, and novel pharmacological target for the treatment of MDD.
基金funded by the Russian Science Foundation(RSF)(research project N°16-15-10053(extension)).
文摘The impact of various vitamin D3(VD3)doses(1.0,2.5,or 5 mg/kg,s.c.)in mitigating the negative consequences of chronic unpredictable mild stress(CUMS)was investigated.Adult female rats with long-term estrogen deficiency were assessed using the sucrose preference test(SPT),the elevated plus-maze(EPM),the light/dark test(LDT),and the open-field test(OFT)to measure anhedonia-like and anxiety-like behavior.The corticosterone(CS)and adrenocorticotrophic hormone(ACTH)concentrations in blood serum and the brain-derived neurotrophic factor(BDNF)expression in the hippocampus of long-term ovariectomized(OVX)rats were measured by ELISA kits and/or western blotting.Treatment with VD3(5.0 mg/kg),similarly to fluoxetine(10.0 mg/kg),significantly reduced the anhedonia profile in the SPT and anxiety-like behavior in the EPM and LDT,and CS and ACTH levels in blood serum.It also elevated BDNF levels in the hippocampus of long-term OVX/CUMS compared to OVX/CUMS/solvent rats.Thus,these findings suggest that VD3(5.0 mg/kg)administration might attenuate the anxiety-like profile in long-term OVX adult rats subjected to the CUMS.This might occur via activation of the BDNF signaling pathway in the hippocampus and via restoration of CS and ACTH levels in blood serum.
文摘The ability of an organism to adapt to aversive stressful situations or life challenging circumstances is very crucial to its state of health and survival. However, breakdown in adaptation due to persistent uncontrollable stress, leads to impairment of bodily functions and onset of a variety of pathological disorders especially memory decline. This study was designed to evaluate the effect of Jobelyn®(JB), a potent antioxidant sorghum-based food supplement on unpredictable chronic mild stress (UCMS)-induced memory impairment in mice. Male Swiss mice were given JB (5 - 50 mg/kg, p.o) 30 min prior to exposure to UCMS for 14 consecutive days before testing for memory. Thereafter, the serum corticosterone level was estimated by using ELISA kits. The levels of malondialdehyde (MDA) and glutathione (GSH) as well as acetylcholinesterase activity were estimated in the brain homogenate using spectrophotometer. Histology of the brain tissues and estimation of the populations of viable neurons in the hippocampal region were done after staining with hematoxyline and eosin. Our results showed that JB reversed memory impairment and suppressed corticosterone concentrations induced by UCMS. Moreover, JB reduced oxidative stress in the brain of UCMS-mice as shown by decreased MDA levels and elevated GSH concentrations. It also decreased brain acetylcholinesterase activity when compared with chronic stress group (p < 0.05). Furthermore, JB (5 - 10 mg/kg, p.o) offered significant protection against UCMS-induced degeneration and death of neuronal cells of the cornu ammonis 3 (CA3) of the hippocampal region of the brain indicating neuroprotection. Taken together, these findings suggest that JB attenuates memory deficits induced by UCMS in mice and may be useful therapeutically for stress-related cognitive dysfunctions. The reduction in the levels of serum corticosterone, antioxidation, neuroprotection and inhibition of cholinesterase enzyme might be contributing significantly to the positive effect of JB on memory in mice exposed to unpredictable chronic mild stress.
基金supported by the National Natural Science Foundation of China(Nos.81673881 and 81202644)Hebei Province Natural Science Foundation Traditional Chinese Medicine Joint Fund Cultivation Project(No.H2022423375)Graduate Innovation Project of Hebei University of Chinese Medicine in 2023(No.XCXZZBS2023003).
文摘Background:Depression is becoming increasingly prevalent around the world,imposing a substantial burden on individuals,families,as well as society.Quercetin is known to be highly effective in treating depression.However,additional research is needed to dissect the mechanisms of its anti-depressive effects.Methods:For this study,Sprague-Dawley(SD)rats were randomized into the control,model,quercetin,or fluoxetine group.The latter three groups were exposed to chronic unpredictable mild stress(CUMS)for 42 d.The first two groups received saline solution daily via oral gavage.Meanwhile,the quercetin group was orally administered a quercetin suspension(52.08 mg/kg)every day,while the fluoxetine group was orally administered a fluoxetine solution(2.08 mg/kg).Here,fluoxetine served as the positive control drug to compare the therapeutic effects of quercetin.The experimental period was 6 weeks.Depressive behaviors in rats were assessed through various physiological and behavioral measures.Additionally,pathological changes in hippocampal tissues were examined using Nissl staining.Serum cytokines were detected using an enzymelinked immunosorbent assay(ELISA),and immunohistochemistry was employed to quantify the levels and integral optical density(IOD)values of ionized calcium binding adaptor molecule-1(Iba-1)expression in the brain.Real-time fluorescence quantitative PCR(RT-qPCR)was utilized to evaluate the mRNA levels of inflammatory indicators as well as toll-like receptor 4(TLR4),and nuclear factor-κappa B P65(NF-κB P65)in hippocampus.Western blot(WB)technique was employed to observe the protein levels of TLR4,NF-κB P65,and phospho-NF-κB P65(p-NF-κB P65).Results:After 42 d of exposure to CUMS,rats exhibited a slow increase in body weight,a reduction in food intake,an abnormal preference for sugar water,and aberrant open-field behaviors.Pathological analysis revealed the disintegration,rupture,interruption,and disorganization of hippocampal neuronal cells after CUMS exposure,along with a decrease in Nissl bodies in the CA1 region.This was accompanied by the elevated expression of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6)in the serum and the upregulation of IL-1β,IL-6,and TNF-αmRNA expression in the hippocampus.Increases in Iba-1-positive cells and the IOD values of Iba-1 were detected in hippocampal microglia.Furthermore,TLR4 and NF-κB P65 mRNA and protein levels were upregulated in hippocampal tissues.Quercetin,an antidepressant,could alleviate depression-like symptoms in rats and downregulate inflammatory factors associated with the TLR4/NF-κB signaling pathway in hippocampal microglia,and its therapeutic effect was comparable to fluoxetine.Conclusion:In rat models of CUMS,quercetin may act as an antidepressant by inhibiting inflammation in hippocampal microglia via TLR4/NF-κB signaling pathway.These results offer experimental and theoretical support for applying quercetin in the clinical management of depression.
基金This research was financially supported by the National High Technology Research and Development Program 863 of China (Grant No. 2008AA04Z211), the National Natural Science Foundation of China (Grant No.60901074, Grant No.61175107) and State Key Laboratory of Robotics and System (Grant No. SKLRS 200901A02).
文摘A CPG control mechanism is proposed for hopping motion control of biped robot in unpredictable environment. Based on analysis of robot motion and biological observation of animal's control mechanism, the motion control task is divided into two simple parts: motion sequence control and output force control. Inspired by a two-level CPG model, a two-level CPG control mechanism is constructed to coordinate the drivers of robot joint, while various feedback information are introduced into the control mechanism. Interneurons within the control mechanism are modeled to generate motion rhythm and pattern promptly for motion sequence control; motoneurons are modeled to control output forces of joint drivers in real time according to feedbacks. The control system can perceive changes caused by unknown perturbations and environment changes according to feedback information, and adapt to unpredictable environment by adjusting outputs of neurons. The control mechanism is applied to a biped hopping robot in unpredictable environment on simulation platform, and stable adaptive motions are obtained.
基金Supported by National Natural Science Foundation of China(No.81574038)Shenzhen Science and Technology Program(No.JCYJ20180508152437368)Sanming Project of Medicine in Shenzhen,China(No.SZSM201612049)。
文摘Objective:To investigate the antidepressant-like effects of Chaihu Shugan Powder(CSP,柴胡疏肝散)and to explore its underlying mechanisms.Methods:Thirty-two Sprague-Dawley rats were randomly divided into control(CON),chronic unpredictable mild stress(CUMS),fluoxetine(FLU),and CSP groups,8 rats in each group.All of the rats except for those in the control group were subjected to 3 consecutive weeks of CUMS to establish the depression model.The open field test(OFT),forced swimming test(FST),and sucrose preference test were used to assess the anti-anxiety and antidepressant effects of CSP.Terminal deoxynucleotidyl transferase(Td T)d UTP nick-end labeling was used to determine the apoptosis rate in the hippocampal tissues.The m RNA and protein levels of glucose-regulated protein(GRP)78,spliced X-box-binding protein(XBP)-1,CCAAT/enhancerbinding protein homologous protein(CHOP),caspase-12,and c-Jun N-terminal kinase(JNK)in the hippocampus of rats were evaluated by real-time PCR and Western blot analysis,respectively.Results:Administration of CSP alleviated anxiety and depression-like behavior in CUMS rats,as revealed by enhanced time and distance in the center of the OFT(P<0.05),an increased preference for sucrose,and longer swimming time and shorter immobility time during the FST(all P<0.05).In addition,CSP treatment significantly reduced the rate of apoptosis in rat hippocampal neurons(P<0.05).The m RNA and protein expression levels of GRP78,spliced XBP-1,and CHOP were down-regulated along with the expression of caspase-12 and cleaved caspase-12 proteins(all P<0.05),whereas total and phosphorylated JNK1 protein levels did not differ significantly between control and CSP-treated rats.Conclusion:CSP can improve depression-like behavior in rats exposed to CUMS,possibly by suppressing CHOP and caspase-12 mediated apoptosis in the rat hippocampus.
文摘Background Up to now there have been no satisfactory drugs to treat psychiatric disorders, and now bioactive compound from entomagenous fungi (BCEF0083) is a new type of bioactive compound from entomopathogenic fungi. Our previous investigations have shown that BCEF has an inhibition effect on monoamine oxidase. So, BCEF may be a latent antidepressant. This study aimed at observing the antidepressant effects and its mechanism of BCEF in the chronic unpredictable stress models in mice. Methods The antidepressant effects of BCEF were examined on the chronic unpredictable stress models in mice. Sixty mice were randomly divided to six groups. Animals were housed and isolated except saline group. Mice were exposed to different stressors per day randomly from day 1 to day 21. Body weight were weighed on day 1,day 10 and on day 21 during the 21-day stress procedure. Awarding response was detected by using method of calculating the 24-hour consumption of saccharum water. Step through test was used to evaluate the behavioral response. AVP contents in plasma were also detected by using radioimmunoassays. Results Chronic unpredictable stress resulted in a significant decrease of the body weight and could apparently cause escape behavior disturbance and gradual reduction of sensitivity to reward in animal models. Drug treatment (BCEF 25, 50, 100 mg/kg) could significantly ameliorate the decreased body weight and effectively reverse the escape behavior disturbance. The gradual reduction of sensitivity to reward, the anhedonic state, was also effectively reversed by BCEF. BCEF (50, 100 mg/kg) could also effectively restore the AVP content in the plasma.Conclusions This evidence suggests that BCEF can effectively inhibit the depression behavior and show strong antidepressant effect. BCEF can effectively restore the plasma AVP release and this may be an important mechanism of its antidepressant effect.
基金This research was supported by the Key Basic Research and Development Plan of P.R.China(2016YFC050080502)the National Natural Science Foundation of P.R.China(31370705,31570416).
文摘Aims Seed dormancy and the soil seed bank are crucial to plant regeneration strategy,especially in semiarid ecosystems with unpredictable precipi-tation.the aim of this study was to investigate how seed dormancy is controlled by environmental factors and how it is correlated with the soil seed bank and regeneration of the perennial legume Oxytropis race-mosa,a dominant perennial herb in Mu Us Sandland of semiarid China.Methods Germination and imbibition experiments on fresh intact and scarified seeds of O.racemosa were used to identify physical dormancy(PY)in seeds of this species.Soil seed bank dynamics,timing of seedling emer-gence and the fate of buried seeds in the natural habitat were investigated.Important Findings PY was broken by mechanical scarification or wet heat/ice water cycles but not solely by dry heat or wet heat treatment.the soil seed bank exhibited seasonal changes in the number of seeds,which was highest in September and lowest in July.Seeds buried at different sand depths gradually lost dormancy;20-42%of the seeds remained dormant after 20 months of burial.Dormancy break occurs grad-ually throughout the year.Our results indicate that O.racemosa exhibits hardcoatedness heterogeneity that spreads germination of a seed cohort between seasons and years in the semiarid environ-ment,where the amount of precipitation during the growing season is highly variable.
文摘With the support by the National Natural Science Foundation,agroup of international researchers led by Duan HaoHong(段昊泓),Li Jun(李隽)at Tsinghua University,and Edman Tsang and Dermot O’Hare at University of Oxford discovered a novel catalytic promoter role of molecular nitrogen(N2)in biomass transformation,which was published in Nature Catalysis(2019,2:1078—1087).
基金supported by the National Natural Science Foundation of China,Nos.81772438,81974357the Guangzhou Municipal Science and Technology Program,No.202206010197(all to YL)。
文摘The spleen is critical for immunity.It is the largest immune organ and immune center in the peripheral system.While the relationship between behavior and immunity has been demonstrated in physiology and diseases,the role of the spleen in behavior is not clear.To investigate the effects of the spleen on behaviors,we performed a refined splenectomy procedure on C57BL/6J mice and performed an open field test,circadian rhythm test,elevated plus maze,sucrose preference test,and Barnes maze test.Splenectomy did not induce changes in general locomotion,circadian rhythms,learning and memory,or depression/anxiety-related behaviors.To further investigate the effects of spleen on stress susceptibility,we established mouse models of depression through chronic unpredictable mild stress.The behavioral performances of mice subjected to splenectomy showed no differences from control animals.These findings suggest that splenectomy does not cause changes in baseline behavioral performance in mice.
基金supported by the Tsinghua University 2021 Doctoral Summer Projectsupported by the National Key R&D Program of China (No. 2018YFE0301102)National Natural Science Foundation of China (Nos. 11875020 and 11875023)。
文摘The plasma optical boundary reconstruction technique based on Hommen's theory is promising for future tokamaks with high parameters. In this work, we conduct detailed analysis and simulation verification to estimate the ‘logic loophole' of this technique. The finite-width effect and unpredictable errors reduce the technique's reliability, which leads to this loophole. Based on imaging theory, the photos of a virtual camera are simulated by integrating the assumed luminous intensity of plasma. Based on Hommen's theory, the plasma optical boundary is reconstructed from the photos. Comparing the reconstructed boundary with the one assumed, the logic loophole and its two effects are quantitatively estimated. The finite-width effect is related to the equivalent thickness of the luminous layer, which is generally about 2-4 cm but sometimes larger. The level of unpredictable errors is around 0.65 cm. The technique based on Hommen's theory is generally reliable, but finite-width effect and unpredictable errors have to be taken into consideration in some scenarios. The parameters of HL-2M are applied in this work.
基金supported by grants from the National Natural Science Foundation Youth Project of China(No.81703716)Jiangxi Science Foundation for Distinguished Young Scholars(No.20224ACB216019)+5 种基金the Natural Science Foundation of Jiangxi Province(No.20202BABL206151 and No.20202BABL216026)Youth Talents Project of Jiangxi Science and Technology Normal University(No.2017QNBJRC006)Doctoral Startup Fund of Jiangxi Science and Technology Normal University(No.2019BSQD015)Department Education Science and Technology Research Project of Jiangxi(No.GJJ201134)the Open Project of Jiangxi Provincial Key Laboratory of Drug Design and Evaluation(No.JKD-KF-2104)the National Undergraduate Training Program for Innovation of China(No.202211318024).
文摘Objective Patients with chronic ulcerative colitis(UC)often have mental symptoms such as depression and anxiety,and stress can lead to gastrointestinal diseases.However,the correlation between mental stress and UC is unclear.In this paper,chronic unpredictable mild stress(CUMS)was utilized to evaluate the involvement of mental factors in the pathogenesis of UC.Methods The CUMS model was used to evaluate the direct/indirect involvement of mental factors in the pathogenesis of UC.The behavior was evaluated by the open field,forced swimming,and tail suspension tests.Body weight,the disease activity index(DAI)score,colon length,and HE staining of colon tissue were used to evaluate the action of CUMS and fluoxetine.Results The results showed that weight loss and the DAI score increased in CUMS mice,but they had no meaningful effect on colon length and morphological structure of colon tissue.However,CUMS aggravated dextran sulfate sodium(DSS)-induced colon length shortening and colon morphological structure damage.Fluoxetine significantly improved the DAI score,shortened colon length,and damaged morphology and structure of the colons induced by CUMS combined with DSS in mice.Fluoxetine also decreased the level of IL-6 in the serum and the TNF-αand IFN-γlevels of colon tissue.Fluoxetine simultaneously improved behavioral abnormalities induced by CUMS combined with DSS in mice.Conclusion CUMS aggravated the UC symptoms induced by DSS,and fluoxetine could improve the UC symptoms due to its improvement in the inflammatory level and behavioral abnormalities.
基金Qinghai Provincial Key R&D and Transformation Plan (No.2021?SF?C21)。
文摘Objective:To explore the effects of CUMS combined with CRS on mouse hippocampal glial cells and synaptic plasticity-related proteins. Methods: Forty mice were randomly divided into normal group (n=20) and model group (n=20). The model group used CUMS combined with CRS to prepare a mouse model of depression for 7 weeks. The behavioral evaluation of the mice at 3 weeks and 7 weeks after modeling was performed by sugar water preference test, open field test and tail suspension test. After the experiment, the samples were collected, and the content of TNF-a in the hippocampus of mice was detected by enzyme-linked immunosorbent assay. Immunohistochemical method was used to detect the Iba-1 and GFAP MOD values of mouse hippocampal CA1 area, CA3 area and DG area. Western blot was used to detect the protein expression of Iba-1, GFAP, SYN1 and PSD-95 in the hippocampus. fluorescence quantitative PCR method was used to detect the expression of SYN1, PSD-95 mRNA in hippocampus. Results: At the 3rd week after modeling, the body weight, sugar water preference rate, total distance moved, number of standing uprights, and stay time in the central area of the mice in the model group were all lower than those in the normal group (P<0.05), and the tail suspension immobility time was longer than that in the normal group (P<0.01). After 7 weeks of modeling, the body weight, sugar water preference rate, total distance moved, number of erection times, central area residence time, and average movement speed of the mice in the model group were lower than those in the normal group (P< 0.05), the tail suspension immobility time was longer than that in the normal group (P<0.01). The contents of TNF-a in the hippocampus were higher than those in the normal group (P<0.05). The GFAP MOD value and the relative expression of GFAP protein in hippocampal CA1, CA3 and DG regions were significantly lower than those in the normal group (P<0.05). The Iba-1 MOD value and the relative expression of Iba-1 protein in hippocampal CA1, CA3 and DG regions were significantly higher than those in the normal group (P<0.05). The relative expression of SYN1 and PSD-95 protein and the relative expression of SYN1 and PSD-95 mRNA in the hippocampus were significantly lower than those in the normal group (P<0.05). Conclusion: After 3 weeks of CUMS and CRS modeling, the depression-like behavior of mice appeared, and the depression of mice was more obvious after 7 weeks of modeling. The depression mouse model made by CUMS combined with CRS method may be related to increased hippocampal inflammation, excessive activation of microglia, decreased number of astrocytes and decreased synaptic plasticity.
基金supported in part by National Key R&D Program of China (No.2020YFB1807802)National Natural Science Foundation of China (Nos.61971148,U22A2054)。
文摘Digital twin is an essential enabling technology for 6G connected vehicles.Through highfidelity mobility simulation,digital twin is expected to make accurate prediction about the vehicle trajectory,and then support intelligent applications such as safety monitoring and self-driving for connected vehicles.However,it is observed that even if a digital twin model is perfectly derived,it might still fail to predict the trajectory due to tiny measurement noise or delay in the initial vehicle locations.This paper aims at investigating the sources of unpredictability of digital twin.Take the car-following behaviors in connected vehicles for case study.The theoretical analysis and experimental results indicate that the predictability of digital twin naturally depends on its system complexity.Once a system enters a complex pattern,its longterm states are unpredictable.Furthermore,our study discloses that the complexity is determined,on the one hand,by the intrinsic factors of the target physical system such as the driver’s response sensitivity and delay,and on the other hand,by the crucial parameters of the digital twin system such as the sampling interval and twining latency.
基金supported by a grant from the Experimental Animal Science and Technology Project of Zhejiang Province in China,No.2012C37083
文摘Post-stroke depression is associated with reduced expression of brain-derived neurotrophic factor (BDNF). In this study, we evaluated whether BDNF overexpression affects depression-like behavior in a rat model of post-stroke depression. The middle cerebral artery was occluded to produce a model of focal cerebral ischemia. These rats were then subjected to isolation-housing combined with chronic unpredictable mild stress to generate a model of post-stroke depression. A BDNF gene lentiviral vector was injected into the hippocampus. At 7 days after injection, western blot assay and real-time quantitative PCR revealed that BDNF expression in the hippo- campus was increased in depressive rats injected with BDNF lentivirus compared with depressive rats injected with control vector. Furthermore, sucrose solution consumption was higher, and horizontal and vertical movement scores were increased in the open field test in these rats as well. These findings suggest that BDNF overexpression in the hippocampus of post-stroke depressive rats alleviates depression-like behaviors.
基金supported by the National Natural Science Foundation of China,No.81071093,81171268
文摘Shuganjieyu capsule has been approved for clinical treatment by the State Food and Drug Ad-ministration of China since 2008. In the clinic, Shuganjieyu capsule is often used to treat mild to moderate depression. In the rat model of depression established in this study, Shuganjieyu capsule was administered intragastrically daily before stress. Behavioral results conifrmed that depressive symptoms lessened after treatment with high-dose (150 mg/kg) Shuganjieyu capsule. Immunohistochemistry results showed that high-dose Shuganjieyu capsule signiifcantly increased phosphorylation levels of phosphorylation cyclic adenosine monophosphate response element binding protein and brain-derived neurotrophic factor expression in the medial prefrontal cortex and hippocampal CA3 area. Overall, our results suggest that in rats, Shuganjieyu capsule effec-tively reverses depressive-like behaviors by increasing expression levels of neurotrophic factors in the brain.
基金supported by the National Natural Science Foundation of China,No.30370537
文摘Adult BALB/c mice, individually housed, were stimulated with nine different stressors, arranged randomly, for 4 continuous weeks to generate an animal model of chronic stress. In chronically stressed mice, spontaneous locomotor activity was significantly decreased, escape latency in the Morris water maze test was prolonged, serum levels of total thyrotropin and total triiodothyronine were significantly decreased, and dopamine and norepinephrine content in the pallium, hippocampus and hypothalamus were significantly reduced. All of these changes were suppressed, to varying degrees, by L-tyrosine supplementation. These findings indicate that the neuroendocrine network plays an important role in chronic stress, and that L-tyrosine supplementation has therapeutic effects.