Interplay between microglia and environmental risk factors in Alzheimer's disease

Alzheimer s disease,among the most common neurodegenerative disorders,is chara cterized by progressive cognitive impairment.At present,the Alzheimer’s disease main risk remains genetic ris ks,but major environmental fa ctors are increasingly shown to impact Alzheimer’s disease development and progression.Microglia,the most important brain immune cells,play a central role in Alzheimer’s disease pathogenesis and are considered environmental and lifestyle"sensors."Factors like environmental pollution and modern lifestyles(e.g.,chronic stress,poor dietary habits,sleep,and circadian rhythm disorde rs)can cause neuroinflammato ry responses that lead to cognitive impairment via microglial functioning and phenotypic regulation.However,the specific mechanisms underlying interactions among these facto rs and microglia in Alzheimer’s disease are unclear.Herein,we:discuss the biological effects of air pollution,chronic stress,gut micro biota,sleep patterns,physical exercise,cigarette smoking,and caffeine consumption on microglia;consider how unhealthy lifestyle factors influence individual susceptibility to Alzheimer’s disease;and present the neuroprotective effects of a healthy lifestyle.Toward intervening and controlling these environmental risk fa ctors at an early Alzheimer’s disease stage,understanding the role of microglia in Alzheimer’s disease development,and to rgeting strategies to to rget microglia,co uld be essential to future Alzheimer’s disease treatments.

Brain region-specific roles of brain-derived neurotrophic factor in social stress-induced depressive-like behavior

Brain-derived neurotrophic factor is a key factor in stress adaptation and avoidance of a social stress behavioral response.Recent studies have shown that brain-derived neurotrophic factor expression in stressed mice is brain region–specific,particularly involving the corticolimbic system,including the ventral tegmental area,nucleus accumbens,prefrontal cortex,amygdala,and hippocampus.Determining how brain-derived neurotrophic factor participates in stress processing in different brain regions will deepen our understanding of social stress psychopathology.In this review,we discuss the expression and regulation of brain-derived neurotrophic factor in stress-sensitive brain regions closely related to the pathophysiology of depression.We focused on associated molecular pathways and neural circuits,with special attention to the brain-derived neurotrophic factor–tropomyosin receptor kinase B signaling pathway and the ventral tegmental area–nucleus accumbens dopamine circuit.We determined that stress-induced alterations in brain-derived neurotrophic factor levels are likely related to the nature,severity,and duration of stress,especially in the above-mentioned brain regions of the corticolimbic system.Therefore,BDNF might be a biological indicator regulating stress-related processes in various brain regions.

Double role of depression in gastric cancer:As a causative factor and as consequence

In this editorial we comment on the article“Hotspots and frontiers of the rela-tionship between gastric cancer and depression:A bibliometric study”.Gastric cancer(GC)is a common malignancy in the digestive system with increased mortality and morbidity rates globally.Standard treatments,such as gastrectomy,negatively impact patients'quality of life and beyond the physical strain,GC patients face psychological challenges,including anxiety and depression.The prevalence of depression can be as high as 57%,among gastrointestinal cancer patients.Due to the advancements in treatment effectiveness and increased 5-year overall survival rates,attention has shifted to managing psychological effects.However,the significance of managing the depression doesn’t lie solely in the need for a better psychological status.Depression leads to chronic stress acti-vating the sympathetic nervous system and the hypothalamus-pituitary-adrenal axis,leading release of catecholamines inducing tumor proliferation,migration,and metastasis,contributing to GC progression.The dysregulation of neurotrans-mitters and the involvement of various signaling pathways underscore the complex interplay between depression and GC.Comprehensive strategies are required to address the psychological aspects of GC,including region-specific interventions and increased monitoring for depression.Understanding the intricate relationship between depression and GC progression is essential for developing effective therapeutic strategies and improving overall outcomes for patients facing this complex disease.In this Editorial we delve into double role of depression in the pathogenesis of GC and as a complication of it.

Antidepressant effects of Peiyuan Jieyu formula in a mouse model of chronic stress in conjunction with lipopolysaccharide-induced depression

Objective:To explore the mechanism of the Peiyuan Jieyu formula in treating depression by assessing its impact on a lipopolysaccharide-induced(LPS-induced)depression mouse model.Methods:We created a mouse model of depression by exposing mice that had previously received chronic stress to intraperitoneal LPS injections.The mice were divided into the following groups:control,model,fluoxetine,Tiansi Yin,Sini powder,and low-,medium-,and high-dose Peiyuan Jieyu formula groups.Forced swim and tail suspension tests were used to assess the efficacy of the depression(despair)model,and weight gain rates were also measured.Furthermore,serum levels of various depression and inflammation-associated molecules,including tumor necrosis factor-a(TNF-a),interferon-γ(IFN-γ),tryptophan,5-hydroxytryptamine,kynurenine(KYN),and kynurenic acid(KA)were assessed.Furthermore,the expression levels of ionic calcium-binding adaptor molecule-1(IBA-1)and indoleamine 2,3-dioxygenase(IDO)mRNA in hippocampal microglia were measured.Results:The model group displayed greater despair-associated immobility,which was shortened in response to various doses of Peiyuan Jieyu formula.Furthermore,formula administration significantly reduced serum TNF-a levels and hippocampal IDO mRNA expression.The high formula dose also reduced IFN-γand IBA-1 levels,the latter was also decreased in response to the medium formula dose.However,the low formula dose reduced serum KYN level and KYN/tryptophan(TRP)and KYN/KA ratios.Conclusion:The Peiyuan Jieyu formula holds immense potential in treating depression in a mouse model,potentially inhibiting inflammation and improving TRP-KYN metabolic disorders.

Quercetin regulates depression-like behavior in CUMS rat models via TLR4/NF-κB signaling

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.

Comparative proteomic analysis of hippocampal proteins from chronic stressed rats

Chronic stress can induce hippocampus injury such as neuron loss and dendrite atrophy,but its mechanism and molecular basis remain unclear up to now.To understand the molecular mechanism on protein level and find the crucial proteins which correlated with chronic

Splenectomy does not affect mouse behaviors

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.

Transcriptome analysis reveals the mechanism of chronic heat stress on meat quality of broilers

Background:Chronic heat stress has a negative impact on poultry meat quality.Although this has been extensively investigated,previous studies have primarily focused on metabolic alterations and oxidative stress in the pectoralis major(PM)muscle under chronic heat stress,and not all of the underlying molecular mechanisms are completely understood.Methods:A total of 144 male Arbor Acres broilers(28 d old)were randomly allocated into 3 treatment groups:(1)the normal control(NC)group,with broilers raised at 22℃and fed a basal diet;(2)the heat stress(HS)group,with birds raised at 32℃and fed a basal diet;and(3)the pair-fed(PF)group,with birds raised at 22℃and fed the amount of feed equal to the feed consumed on the previous day by the HS group.The experiment lasted for 14 d.Results:Chronic heat stress decreased the average daily feed intake and average daily gain,increased feed:gain ratio(P<0.05);and increased drip loss,cooking loss,shear force,hardness,and decreased p H,redness(a*);and springiness of PM muscle(P<0.05).Furthermore,chronic heat stress decreased muscle fiber density,increased connective tissue,and led to intracellular vacuolation.The transcriptome analyses indicated that the effect of chronic heat stress on meat quality was not only related to metabolism and oxidative stress,but also to signal transduction,immune system,transport and catabolism,cell growth and death,and muscle structure.Conclusions:Chronic heat stress has a negative impact on the growth performance,meat quality,and the PM muscle structure of broilers.Transcriptome analysis revealed a comprehensive understanding of the mechanism of the chronic heat stress-induced deterioration of broiler meat quality at the transcriptional level.

Effects of CUMS combined with CRS on hippocampal glial cells and synaptic plasticity in depressed mice

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.

Fluoxetine Ameliorates the Aggravation of UC Symptoms in C57BL/6 Mice Induced by CUMS

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.

Shuganheweitang Ameliorates Chronic Unpredictable Mild Stress-Induced Depression-Like Behaviors in Rats through the PI3K/AKT/mTOR Pathway: Involvement of Amino Acids, Glycerophospholipids, and Energy Metabolism

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.

Hippocampal gene expression in a rat model of depression after electroacupuncture at the Baihui and Yintang acupoints

Preliminary basic research and clinical findings have demonstrated that electroacupuncture ther- apy exhibits positive effects in ameliorating depression. However, most studies of the underlying mechanism are at the single gene level; there are few reports regarding the mechanism at the whole-genome level. Using a rat genomic gene-chip, we profiled hippocampal gene expression changes in rats after electroacupuncture therapy. Electroacupuncture therapy alleviated depres- sion-related manifestations in the model rats. Using gene-chip analysis, we demonstrated that electroacupuncture at Baihui （DU20） and Yintang （EX-HN3） regulates the expression of 21 genes. Real-time PCR showed that the genes Vgf, lgf2, Trnp32, Loc500373, Hifla, Folrl, Nrnb, and Rtn were upregulated or downregulated in depression and that their expression tended to nor- malize after electroacupuncture therapy. These results indicate that electroacupuncture at Baihui and Yintang modulates depression by regulating the expression of particular genes.

The effects of Xingnao Jieyu capsules on post-stroke depression are similar to those of fluoxetine

The Xingnao Jieyu capsule has been shown to effectively relieve neurologic impairments and les- sen depression. It remains poorly understood whether this capsule can be used to treat post-stroke depression. Thus, in the present study, we established a rat model of post-stroke depression using left middle cerebral artery occlusions in combination of chronic unpredictable stress and solitary housing during development. Experimental rats received intragastric perfusion with 0.82, 0.41, and 0.20 g/kg Xingnao Jieyu capsules separately dissolved in 2 mL distilled water. Fluoxetine served as a positive control. The treatment was conducted over 28 days. Sugar water consumption test, open-field test, real-time fluorescent quantitative PCR and immunohistochemical staining results demonstrated that intragastric perfusion with various doses of Xingnao Jieyu capsules increased sugar water consumption, voluntary behaviors and synaptotagmin mRNA and protein expression in rats with post-stroke depression. These therapeutic effects were similar to those of fluoxetine. These results indicate that Xingnao Jieyu capsules upregulate synaptotagmin expression in hip pocampi of rats with post-stroke depression, and exert antidepressant effects.

Overexpression of brain-derived neurotrophic factor in the hippocampus protects against post-stroke depression

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.

Effects of Shuyusan on monoamine neurotransmitters expression in a rat model of chronic stress-induced depression

Shuyusan, a traditional Chinese medicine, was shown to improve depression symptoms and behavioral scores, as well as increase 5-hydroxytryptamine （5-HT）, 5-hydroxyindoleacetic acid, and 5-hydroxytryptophan levels, in a rat model of chronic stress-induced depression. However, dopamine, noradrenalin, and 3-methoxy-4-hydroxyphenylglycol expressions remained unchanged following Shuyusan treatment. Compared with the model group, the number of 5-HT-positive neurons in layers 4-5 of the frontal cortex, as well as hippocampal CA1 and CA3 regions, significantly increased following Shuyusan treatment. These results suggested that Shuyusan improved symptoms in a rat model of chronic stress-induced depression with mechanisms that involved 5-HT, 5-HT metabolite, 5-HT precursor expressions.

L-tyrosine improves neuroendocrine function in a mouse model of chronic stress

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.

Effects of Yulangsan polysaccharide on monoamine neurotransmitters, adenylate cyclase activity and brain-derived neurotrophic factor expression in a mouse model of depression induced by unpredictable chronic mild stress

The present study established a mouse model of depression induced by unpredictable chronic mild stress. The model mice were treated with Yulangsan polysaccharide （YLSPS; 150, 300 and 600 mg/kg） for 21 days, and compared with fluoxetine-treated and normal control groups. Enzyme-linked immunosorbent assay, radioimmunity and immunohistochemical staining showed that following treatment with YLSPS （300 and 600 mg/kg）, monoamine neurotransmitter levels, prefrontal cortex adenylate cyclase activity and hippocampal brain-derived neurotrophic factor expression were significantly elevated, and depression-like behaviors were improved. Open-field and novelty-suppressed feeding tests showed that mouse activity levels were increased and feeding latency was shortened following treatment. Our results indicate that YLSPS inhibits depression by upregulating monoamine neurotransmitters, prefrontal cortex adenylate cyclase activity and hippocampal brain-derived neurotrophic factor expression.

Chronic stress induces ageing-associated degeneration in rat Leydig cells

Several studies have suggested that stress and ageing exert inhibitory effects on rat Leydig cells. In a pattern similar to the normal process of Leydig cell ageing, stress-mediated increases in glucocorticoid levels inhibit steroidogenic enzyme expression that then results in decreased testosterone secretion. We hypothesized that chronic stress accelerates the degenerative changes associated with ageing in Leydig cells. To test this hypothesis, we established a model of chronic stress to evaluate stress-induced morphological and functional alterations in Brown Norway rat Leydig cells; additionally, intracellular lipofuscin levels, reactive oxygen species （ROS） levels and DNA damage were assessed. The results showed that chronic stress accelerated ageing-related changes： ultrastructural alterations associated with ageing, cellular lipofuscin accumulation, increased ROS levels and more extensive DNA damage were observed. Additionally, testosterone levels were decreased. This study sheds new light on the idea that chronic stress contributes to the degenerative changes associated with ageing in rat Leydig cells in vivo.

Neuropeptide Y and leptin receptor expression in the hypothalamus of rats with chronic immobilization stress

In this study, Sprague-Dawley rats were immobilized to a frame for 3 hours a day for 21 days to establish a model of chronic immobilization stress. The body weight and food intake of rats subjected to chronic immobilization stress were significantly decreased compared with the control group. Dual-labeling immunofluorescence revealed that the expression of leptin receptor and the co-localization coeffient in these leptic receptor neurons in the arcuate nucleus of the hypothalamus were both upregulated, while the number of neuropeptide Y neurons was decreased. Chronic immobilization stress induced high expression of leptin receptor in the arcuate nucleus and suppressed the synthesis and secretion of neuropeptide Y, thereby disrupting the pathways in the arcuate nucleus that regulate feeding behavior, resulting in diminished food intake and reduced body weight.

Mechanisms underlying the beneficial effects of Kaiyu Granule for depression

The proprietary Chinese medicine preparation Kaiyu Granule is made of bupleurum, nutgrass ga- lingale rhizome, szechwan Iovage rhizome, turmeric root tuber, white peony alba, cape jasmine fruit fried semen ziziphi jujubae, and prepared liquorice root. It is a common recipe for the clinical treatment of depression in China. In this study, after 21 days of unpredictable stress exposure, Wistar rats exhibited similar behavioral changes to patients with depression. Moreover, G-protein-coupled inwardly rectifying K＋ channel 1 mRNA and protein expression were significantly reduced in rat hippocampal CA1 and CA3 regions. However, G-protein-coupled inwardly rectifying K＋ channel 1 mRNA, protein expression, and rat behavior were clearly better after administration of 12, 8, or 4 g/kg of Kaiyu Granule when depression model rats underwent stress. 12 g/kg of Kaiyu Granule had the most obvious effects on the increased expression of G-protein-coupled inwardly rectifying K＋ channel 1 mRNA and protein in rat hippocampal CA1 and CA3 regions. These results suggested that Kaiyu Granule improved depression by affecting G-protein-coupled inwardly recti- fying K＋ channel 1 expression in the rat hippocampus.