Objectives: The transient receptor potential vanilloid type 1 (TRPV1) is a factor that mediates glial cell response with effects on mitochondrial function. It may affect the occurrence and development of schizophrenia. The aim of this study is to further explore schizophrenia biomarkers by analyzing TRPV1 and oxidative stress in astrocyte-derived extracellular vesicles (ADEs) and peripheral blood mononuclear cells (PBMCs). Methods: A case–control study was conducted. The Positive and Negative Syndrome Scale and the Brief Assessment of Cognition in Schizophrenia (BACS) clinical data were obtained from 50 symptomatic patients with schizophrenia and 50 controls, and fasting peripheral blood samples were collected for the isolation of PBMCs and ADEs. Western blotting was used to assess TRPV1, Sirtuin3 (Sirt3), SOD2, and acetyl-SOD2. Results: The patient group exhibited significantly reduced TRPV1 and Sirt3 expression levels in PBMCs and ADEs compared with the control group. In addition, there was a marked increase in SOD2 and acetyl-SOD2 levels. TRPV1 was negatively correlated with the negative symptom score in the patient PBMCs and ADEs. SOD2 showed positive correlations with the general psychopathology symptom score, and acetyl-SOD2 was positively correlated with the negative symptom score. The BACS total score was positively correlated with TRPV1 levels and negatively correlated with acetyl-SOD2 levels in the patient group. Conclusion: TRPV1 expressions in PBMCs and ADEs were reduced and closely correlated, and TRPV1 levels were associated with psychiatric symptoms and cognitive function in patients with schizophrenia. It was indicated that TRPV1 could be a biomarker for schizophrenia and reflect the disease severity.

Schizophrenia is associated with widespread gray matter reduction. This is influenced by the underlying connectivity, resulting in covarying patterns of structural changes that are more pronounced in treatment-resistant individuals. However, it remains uncertain whether a distinct network of brain regions, with specific neurotransmitter basis, forms the substrate for treatment resistance in schizophrenia. We investigated the structural covariance networks (SCN) in 198 individuals; 55 with treatment-resistant schizophrenia (TRS) and 79 without TRS (non-TRS) in active symptomatic phase, and 64 healthy controls (HC) using Calhoun’s Source-Based Morphometry. We mapped the putative neurotransmitter basis of the SCNs using a PET-based chemoarchitectural atlas. Twelve independent components (i.e., SCNs) were identified. A prefrontal-limbic SCN had lower gray matter volume (GMV) in TRS compared to HC and non-TRS (F = 7.757, p < 0.001, FDR-corrected). Spatial correlation with chemoarchitectural atlas revealed predominant contributions from serotonergic [5HT1b and 5HT2a], glutamatergic [mGluR5], histaminergic [H3], and opioid [MOR] receptors for this TRS-related SCN (all pspin-permutation < 0.05, FDR-corrected). A different SCN comprised of dorsal fronto-temporal and parieto-occipital regions, not associated with any specific neurotransmitter distribution, exhibited reduced GMV in both TRS and non-TRS groups vs. HC (F = 7.239, p < 0.001, FDR-corrected). Amidst the generic GMV reduction that is shared with non-TRS patients, patients with TRS have specific prefrontal-limbic structural deficits with a unique non-dopaminergic chemoarchitecture. These findings indicate a putative molecular and structural basis for poor treatment response, guiding the development of second- and third-line pharmacotherapies for TRS.

Maternal separation (MS) during early life can induce behaviors in adult animals that resemble those seen in schizophrenia, manifesting cognitive deficits. These cognitive deficits may be indicative of oxidative stress linked to mitochondrial dysfunction. However, there is limited understanding of the molecular mechanisms regulating mitochondria in neural circuits that govern cognitive impairment relevant to schizophrenia, and their impact on neuronal structure and function. A 24-h MS rat model was utilized to simulate features associated with schizophrenia. Schizophrenia-associated behaviors and cognitive impairment were assessed using the open field test, pre-pulse inhibition, novel object recognition test, and Barnes maze test. The levels of mitochondrial proteins were measured using western blot analysis. Additionally, alterations in mitochondrial morphology, reduced hippocampal neuronal spine density, and impaired LTP in the hippocampus were observed. Nicotinamide (NAM) supplementation, administration of honokiol (HNK) (a SIRT3 activator), or overexpression of SIRT3 could inhibit cognitive deficits and cellular dysfunction. Conversely, administration of 3-TYP (a SIRT3 inhibitor) or knocking down SIRT3 expression in control rats led to deficits in behavioral and hippocampal neuronal phenotype. Our results suggest a causal role for the NAD+/SIRT3 axis in modulating cognitive behaviors via effects on hippocampal neuronal synaptic plasticity. The NAD+/SIRT3 axis could be a promising therapeutic target for addressing cognitive dysfunctions, such as those seen in schizophrenia.

抑郁症患者是自杀和非自杀性自伤行为的高发群体.自杀和非自杀性自伤行为的发生可能与脑结构和功能改变有关,但目前其独特的发生机制仍不确定.结构磁共振相关研究提示自杀与非自杀性自伤与额叶和前扣带回体积减少有关,海马及颞叶体积减少与自杀相关,岛叶体积减少与非自杀性自伤有关;静息态功能磁共振相关研究提示自杀和非自杀性自伤均显示默认网络和显著网络之间正向连接减少,而非自杀性自伤者存在额叶边缘系统的改变,以杏仁核为种子点的连接差异可能是区分自杀与非自杀性自伤的一个神经影像学标记;任务态功能磁共振相关研究提示,自杀及非自杀性自伤行为均与自我意识、奖赏环路、情绪处理环路异常有关,而非自杀性自伤还与执行功能、疼痛环路异常有关.本综述从脑结构和脑功能的角度分析抑郁患者自杀与非自杀性自伤行为的神经影像学改变异同,为进一步揭示其发生机制提供依据.

Objective To explore the mechanism of valproate-induced autism-like behavior in Wistar mice based on bioinformatics technique. Methods A total of 4 SPF grade Wistar male mice（300-350 g） and 8 female mice（200-250 g） were selected. The female and male mice were caged overnight at a ratio of 2︰1in 8-10 weeks. The female mice were intraperitoneally injected with 600 mg/kg valproate on the 12.5 days of pregnancy. The newborn mice were included in the valproate group. Open field test, elevated cross maze test, new object recognition test and bead embedding experiment were used to evaluate the success of the model at the 35th day after birth. Another 4 pregnant mice were randomly selected to inject the same amount of normal saline once, and the newborn mice were included in the healthy control group. GSE42904 data set was used to search for genes with different expressions in the brain tissues of mice receiving valproate and methylcellulose.Genetic ontology（GO）, Kyoto Encyclopedia of Genes and Genome（KEGG）, GO/KEGG（combined with LogFC） and Gene Set Enrichment Analysis（GSEA） were used for enrichment analysis of differential genes. Quantitative real-time polymerase chain lock reaction（Q-PCR） was used to verify the expression of differential genes in the brain tissue of model mice in valproate group. Finally, 14 young mice in the valproate group and 7 young mice in the healthy control group were included. Results Compared with the control group, the time of entering the central area and the number of body extensions decreased in the open field experiment, the recognition index decreased in the new object recognition experiment, and the number of buried beads increased in the bead embedding experiment, and all the differences were statistically significant（P ＜ 0.05）. In the elevated cross maze test, there was no statistically significant difference between the valproate group and the healthy control group in the number of times of entering the open arm and the total distance of movement（P＞0.05）, indicating successful modeling. According to the analysis of GSE42904 data set, there are 267 genes in line with | Log2（FC） | ＞ 1and P ＜ 0.05, and these differential genes are mainly concentrated in metabolic pathway. The differential genes glutathione S-transferase α 3（Gsta 3）, gamma-glutamyl transferase 7（Ggt 7） and glucose-6-phosphate dehydrogenase（G6pd） in the glutathione metabolic pathway were verified. It was found that there was no statistical significance in the difference in mRNA expressions between Gsta 3 and Ggt 7（P＞0.05）. The mRNA expression level of G6pd gene in valproate group was significantly lower than that in healthy control group, and the difference was statistically significant（P＜0.05）. Conclusions There are differences in the expression of G6pd gene in the valproate rat model, and the change in the expression of G6pd gene may be a pathogenic factor of autism spectrum disorder.

目的 基于生物信息学分析精神分裂症发病的可能分子机制,并分析诊断精神分裂症的生物标志物.方法 选择基因表达综合数据库(GEO)中的GSE48072数据集,对31例精神分裂症患者和35名健康对照者的mRNA表达谱进行生物信息学分析.对筛选得到的差异基因进行功能富集分析.采用string数据库构建差异基因的蛋白-蛋白相互作用(PPI)网络,并通过Cytoscape软件筛选关键基因.关键基因的诊断价值通过受试者工作特征(ROC)曲线验证.结果 共筛选出82个差异基因.富集分析结果显示,差异基因主要集中在炎症、免疫调节和不饱和脂肪酸代谢中.筛选后获得CD244、GZMH、GZMA、KLRD1、GZMK 5个关键基因,ROC曲线下面积分别为0.817、0.725、0.724、0.717、0.693.结论 精神分裂症患者存在炎症通路、不饱和脂肪酸以及维生素代谢异常,CD244等5个相关基因的表达变化可作为精神分裂症发病诊断的生物学标志物.

Objective:To explore the effects of embodied emotion priming on attentional bias of individuals with depression tendency.Methods:From June to December 2018, a total of 91 college students with depression tendency were recruited to participate in the experiment.A 3(embodied emotion priming: positive priming, negative priming and no priming) × 2 (emotional face: happy and sad) mixed design was adopted to measure the attentional bias of individuals with depression tendency using the dot probe paradigm. SPSS 22.0 statistical software was used for repeated measurement analysis of variance.Results:In terms of attentional bias, the interaction effect between embodied emotion priming types and emotional faces was significant ( F(2, 88)=5.97, P=0.004, ηp2=0.119). Further simple effect analysis showed that, under the happy-face condition, participants' attentional bias reaction time(△RT) was significantly higher when primed with embodied positive emotion than those primed with embodied negative emotion((14.30±18.23)ms, (-6.53±38.17)ms, P<0.05). The participants' attentional bias △RT was significantly lower when primed with embodied negative emotion than participants with no priming ((-6.53±38.17)ms, (9.16±30.62)ms, P<0.05). Under the sad-face condition, the participants' attentional bias △RT was significantly higher when primed with embodied negative emotion((28.22±35.33)ms) than participants primed with embodied positive emotion((11.71±29.24)ms, P<0.05) and no priming ((7.63±30.60)ms, P<0.05). Conclusion:Embodied emotion priming can affect the attentional bias of individuals with depression tendency.

Although the incidence of major depressive disorder (MDD) is high and its social impact is great, we still know very little about the pathophysiology of depression. The monoamine hypothesis of depression suggests that 5-HT, NE, and DA synergistically affect mood, which is the basis of current drug therapy for depression. However, histamine as a monoamine transmitter is rarely studied. Our review is the first time to illustrate the effect of histaminergic system on depression in order to find the way for the development of new antidepressant drugs. The brain neurotransmitter histamine is involved in MDD, and the brain histaminergic system operates through four receptors. Histamine and its receptors can also regulate the immune response to improve symptoms of depression. In addition, H3R can interact with other depression-related transmitters (including 5-HT, DA, GLU, and MCH); thus, histamine may participate in the occurrence of depression through other neural circuits. Notably, in rodent studies, several H3R and H1R antagonists were found to be safe and effective in alleviating depression-like behavior. To highlight the complex functions of histamine in depression, and reveals that histamine receptors can be used as new targets for antidepressant therapy.

Introduction Childhood maltreatment (CM), stressful life events (SLE), and cognitive emotion regulation strategies (CERS) have been considered crucial in the development of non-suicidal self-injury (NSSI) and major depressive disorder (MDD), but the pathways of this association are not clear. We aim to identify direct effects of CM and SLE on NSSI and depression severity and its indirect effects via CERS in adolescents and young adults with a diagnosis of MDD. Methods A total of 114 patients (aged 14–24 years) with first episode MDD were included and further divided into the NSSI group (n = 56) and non-NSSI group (n = 58) according to the DSM-5 criteria. Diagnostic interviews and self-report measures were conducted to assess CM, SLE, CERS, and diagnose NSSI. Severity of depressive symptoms was measured using the Hamilton Rating Scale (HAMD). The structural equation model was used to assess the pathways. Results MDD patients with NSSI had more frequent family history of mental illness, more experience of CM and SLE, more serious depression, less use of adaptive CERS, and more use of maladaptive CERS. In the final structural equation model (χ2 = 4.82, df = 6, p = 0.57, CFI = 1.0, TLI = 1.10, and RMSEA = 0), the experience of CM and SLE showed a significant indirect effect on NSSI through adaptive CERS. CM and SLE only had direct effects on depression severity. Conclusions NSSI are prevalent in adolescents and young adults with MDD and highly intertwined with CM, SLE, and CERS. Adaptive CERS, not maladaptive CERS may be a possible mechanism relating CM and SLE to NSSI in MDD patients.

目的:探讨人际关系对首次发病青少年抑郁症患者非自杀性自伤行为(NSSI)的影响.方法:纳入80例青少年抑郁症患者,采用青少年自我伤害问卷进行评估,根据有无NSSI,将患者分为伴NSSI组和不伴NSSI组.所有入组对象采用汉密尔顿抑郁量表-17项(HAMD-17)、汉密尔顿焦虑量表(HAMA)评估抑郁及焦虑症状;采用亲子亲密度量表、同伴关系量表、师生关系量表评估样本的人际关系情况,并进行组间比较.采用二元Logistic回归分析人际关系中NSSI的独立风险因素;采用Pearson相关分析分析各变量之间的相关程度.结果:纳入伴NSSI组42例(52.5％),不伴NSSI组38例(47.5％).与不伴NSSI组相比较,伴NSSI组在HAMD-17、HAMA、同伴恐怖自卑、师生关系冲突性方面得分更高(均P<0.01),在亲子亲密度、父亲亲密度、母亲亲密度、同伴关系总分、同伴接受、师生关系亲密性、师生关系支持性、师生关系满意度方面得分更低(均P<0.01或P<0.05).Logistic回归分析显示同伴接受、同伴恐怖自卑、父亲亲密度及母亲亲密度为NSSI的独立风险因素.Pearson相关分析显示,伴NSSI组的NSSI得分与母亲亲密度呈负相关(P<0.01).HAMD-17及HAMA得分与NSSI得分呈正相关(P<0.05或P<0.01),与师生关系冲突性、同伴恐怖自卑呈正相关(P<0.05或P<0.01).在HAMD-17的各项因子与指标中,焦虑/躯体化因子与同伴恐怖自卑及NSSI得分呈正相关(均P<0.01);认知障碍因子与师生关系冲突性及NSSI得分呈正相关(均P<0.05),且与师生关系亲密度、父亲亲密度、母亲亲密度呈负相关(均P<0.05);迟缓因子则与师生关系冲突性以及同伴恐怖自卑呈正相关(均P<0.05).结论:青少年抑郁症患者NSSI行为发生率较高,且与人际关系有关,不良的师生关系、同伴关系和亲子关系,更容易导致出现NSSI行为.

Abstract Background Early life stress (ELS) is associated with the development of schizophrenia later in life. The hippocampus develops significantly during childhood and is extremely reactive to stress. In rodent models, ELS can induce neuroinflammation, hippocampal neuronal loss, and schizophrenia-like behavior. While nicotinamide (NAM) can inhibit microglial inflammation, it is unknown whether NAM treatment during adolescence reduces hippocampal neuronal loss and abnormal behaviors induced by ELS. Methods Twenty-four hours of maternal separation (MS) of Wistar rat pups on post-natal day (PND)9 was used as an ELS. On PND35, animals received a single intraperitoneal injection of BrdU to label dividing neurons and were given NAM from PND35 to PND65. Behavioral testing was performed. Western blotting and immunofluorescence staining were used to detect nicotinamide adenine dinucleotide (NAD+)/Sirtuin3 (Sirt3)/superoxide dismutase 2 (SOD2) pathway-related proteins. Results Compared with controls, only MS animals in the adult stage (PND56–65) but not the adolescent stage (PND31–40) exhibited pre-pulse inhibition deficits and cognitive impairments mimicking schizophrenia symptoms. MS decreased the survival and activity of puberty-born neurons and hippocampal NAD+ and Sirt3 expression in adulthood. These observations were related to an increase in acetylated SOD2, microglial activation, and significant increases in pro-inflammatory IL-1β, TNF-α, and IL-6 expression. All the effects of MS at PND9 were reversed by administering NAM in adolescence (PND35–65). Conclusions MS may lead to schizophrenia-like phenotypes and persistent hippocampal abnormalities. NAM may be a safe and effective treatment in adolescence to restore normal hippocampal function and prevent or ameliorate schizophrenia-like behavior.

Background:Depression in adolescents is more heterogeneous and less often diagnosed than depression in adults. At present, reliable approaches to differentiating between adolescents who are and are not affected by depression are lacking. This study was designed to assess voxel-level whole-brain functional connectivity changes associated with adolescent depression in an effort to define an imaging-based biomarker associated with this condition.Materials and methods:In total, 71 adolescents affected by major depressive disorder (MDD) and 71 age-, sex-, and education level-matched healthy controls were subjected to resting-state functional magnetic resonance imaging (rs-fMRI) based analyses of brain voxel-wise degree centrality (DC), with a support vector machine (SVM) being used for pattern classification analyses.Results:DC patterns derived from 16-min rs-fMRI analyses were able to effectively differentiate between adolescent MDD patients and healthy controls with 95.1% accuracy (136/143), and with respective sensitivity and specificity values of 92.1% (70/76) and 98.5% (66/67) based upon DC abnormalities detected in the right cerebellum. Specifically, increased DC was evident in the bilateral insula and left lingual area of MDD patients, together with reductions in the DC values in the right cerebellum and bilateral superior parietal lobe. DC values were not significantly correlated with disease severity or duration in these patients following correction for multiple comparisons.Conclusion:These results suggest that whole-brain network centrality abnormalities may be present in many brain regions in adolescent depression patients. Accordingly, these DC maps may hold value as candidate neuroimaging biomarkers capable of differentiating between adolescents who are and are not affected by MDD, although further validation of these results will be critical.

大约1/3的抑郁症患者对现有的抗抑郁药无反应而发展为难治性抑郁症(TRD).TRD是一种病程较长的慢性抑郁状态,对当前的治疗方案具有很高的抵抗性,预后较差,给患者家庭及社会带来了沉重负担.现总结当前TRD的治疗方案,对氯胺酮在TRD中使用的证据进行了回顾和分析,重点关注临床给药途径、剂量和疗效持续时间,以及药物的安全性进行讨论,旨在为TRD的临床治疗和氯胺酮的规范使用提供参考依据.

目的:探讨不同性别青少年精神分裂症患者经抗精神病药物治疗4周前后体质量、空腹血糖(FBG)、血尿酸(UA)和血脂代谢的变化.方法:纳入住院治疗的青少年精神分裂症患者186例,男88例,女98例.给予相应的抗精神病药物治疗4周.比较治疗前、后患者体质量、血UA、甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白(LDL)和高密度脂蛋白(HDL)水平及其变化.结果:与治疗前相比,女性青少年治疗4周后体质量、TG、LDL增高(P<0.05),FBG、TC、UA、HDL的血清水平,高TG血症的发生率和高UA血症发生率差异无统计学意义(P>0.05);男性青少年治疗4周后体质量,TG、LDL、UA的血清水平,高TG血症发生率增高(P<0.05),FBG、TC、HDL的血清水平,高UA血症的发生率差异无统计学意义(P>0.05);治疗4周后15.30％的女性青少年和15.91％的男性青少年体重增加了7％.结论:抗精神病药物治疗对青少年精神分裂症患者血脂和血UA代谢有影响,尤其是男性患者.

The glutamate transporter EAAT 2 ( rodent nomencla-ture GLT-1:glutamate transporter 1), which is a predominantly astroglial glutamate transporter in the hippocampus and the pre-frontal cortex , is responsible for the majority of extracellular glu-tamate uptake .The glutamate transporter EAAT 2 can decrease the high levels of glutamate in the synaptic cleft , avoiding gluta-matergic excitotoxicity to damage the glial cells and neurons .&nbsp;Currently, the transporter EAAT2 has become a research hotspot of depression .This article aims to summarize roles of glutamate transporter EAAT2 in the occurrence and treatment of depres-sion.

Objective: The objective was to prospectively assess whether early (ie. 2-week) response to an antipsy-chotics predicts later (ie. 12-week) response in acute schizophrenia patients treated with the paliperidone extend-ed-release (ER) tablets. Methods: Fifty-three acute schizophrenic patients were enrolled and were treated only with paliperidone ER tablets for 12 weeks. The severity of clinical symptoms was evaluated by the Positive and Nega-tive Syndrome Scale (PANSS), and adverse event was assessed using the Treatment Emergent Symptom Scale (TESS) before and 2, 4, 8 and 12 weeks after treatment. Results:The PANSS total scores, positive factors scores, negative factors scores and general factors scores were all significantly lower during the follow-up., and the PANSS total score subtractive score rates were significantly higher. The tendency charts of PANSS total scores and PANSS total score subtractive score rates showed significantly greater changes from baseline. Thirty-five (66.04%) patients fulfilled their early response criterion. Eighteen (33.96%) of patients were identified as non-early responders criteri-on. No severe adverse reaction occurred. Conclusion: The treatment of paliperidone ER tablets for acute schizophre-nia patients works quickly within 2 weeks and can improve the psychotic symptoms continuously. Early response to paliperidone ER treatment may predict the subsequent clinical outcomes.

Objective To investigate the characteristics of the event related potential(ERP) P300 and analyze brain network connections in patients with first-episode depressions.Methods P300 auditory oddball task were administrated on twenty-nine patients and twenty-five healthy controls.The P300 amplitude and latency of two groups were compared,and the brain network connectivity of the two groups were analyzed using Granger's Causality analysis.Results The P300 amplitude in depression group were significantly different from those in control group (C3 of the central regions(15.77±7.35) μV vs (20.90±7.82)μV;C4 of the central regions(16.98±7.21) μV vs (22.11±7.50) μV;P3 of the parietal regions(15.65±6.92) μV vs (19.49±5.73) μV;P4 of the parietal(16.35± 6.46) μV vs P4(19.72±5.18) μV;P=0.009,P=0.007,P=0.017,P=0.024 respectively).However,the P300 latency had no significant difference comparing to the controls(P＞0.05).The results also showed that patients had more connections in the brain network.Conclusion As an effective evaluation index,ERP P300 can play an important role in clinical diagnosis of depression.Patients suffering from depression have significant cognition function deficit.

目的：观察帕利哌酮缓释片治疗急性精神分裂症的疗效,并探讨治疗策略。方法53例精神分裂症患者给予帕利哌酮缓释片,治疗前和治疗后2,4,8,12周分别评定阳性和阴性症状量表( PANSS)、个人和社会功能量表(PSP)、副反应量表(TESS)。结果① PANSS 总分、阳性症状分量表分、阴性症状分量表分和一般因子量表分,均较前一观察点(基线、2周末、4周末、8周末、12周末)减少,差异有统计学意义(均 P<0.01)；PANSS 总分减分率及 PSP 总分均较前一观察点增加,均差异有统计学意义(均 P<0.05)。②12周 PANSS 总分和 PSP 总分变化趋势图显示,4周内变化较8周至12周明显。③35例患者第2周末 PANSS 总分减分率≥20％为早期反应者,其第12周末有32例显效；18例第2周末 PANSS 总分减分率<20％为无早期反应者,其第12周末有9例显效。④治疗后2周末 PANSS 减分率与治疗后第4周末、第8周末、第12周末 PANSS 减分率均显著相关(均 P<0.01)；治疗后2周末 PSP 总分与治疗后第4周末、第8周末、第12周末 PSP 总分均显著相关(均 P<0.01)。结论帕利哌酮缓释片起效快,能12周持续改善精神分裂症患者症状和社会功能,2周内的反应可预测后期疗效。

Objective To explore the effect of different durations of chronic unpredictable mild stress (CUMS) on behaiviors and neurogenesis of bippocampal dentate gyrus in adult rats.Methods (1)Animals were divided into four groups:control group,rats without stress; M1 group,rats subject to CUMS for 1 week; M2 group,rats subject to CUMS for 2 weeks; and M5 group,rats subject to CUMS for 3 weeks.(2) Rats'depression-like behaviors were observed in opening field test and 1％ sucrose preference test was done before and after the experiment of each group.(3) After bahavior test,rats were sacrificed and the hippocampi were isolated.Neurogenesis in hippocampal dentate gyrus was detected by using immunohistochemistry.Results (1) As compared with control group,total diatance (cm) in l0 min/center distance (cm) in 10 min/rearing counts were decreased in MI group (P ＜ 0.05),M2 group (P ＜ 0.05),and M3 group (P ＜0.05).There was no significant difference in the total distance in 10 min/center distance (cm) in 10 min/rearing counts among the M1,M2 and M3 groups (P ＞ 0.05).As compared with control group,levels of total fluid consumption/sucrose consumption/sucrose preference consumption were decreased in MI group (P ＜ 0.05),M2 group (P ＜ 0.05),and M3 group (P ＜ 0.05).There was no significant difference in levels of total fluid consumption among the M1,M2 and M3 groups (P ＞ 0.05) ; (2)As compared with control group (31.75 ± 8.48),BrdU-labeled cells in the dentate gyrus were decreased in M1 group (22.19 ±6.08) (P＜0.05) and M3 group (19.57 ±5.28) (P＜0.05),but there was no significant difference in the levels of BrdU-labeled cells in the dentate gyrus between M1 group and M3 group (P ＞ 0.05).There was no significant difference in the levels of BrdU-labeled cells in the dentate gyrus between M2 group (29.78 ± 6.78) and control group (P ＞ 0.05).Conclusion Different durations of CUMS could lead to the depressive behaviors,but have different influences on the neurogenesis of hippocampal dentate gyrus in adult rats.

目的 观察石杉碱甲对电休克模型大鼠记忆和海马磷酸化细胞外调节蛋白激酶(phosphorylated extracellular-signal related kinase,P-ERK)表达的影响.方法 将大鼠随机分为假电休克对照组和电休克组,2组再随机分为生理盐水对照组(CS组、ES组)和石杉碱甲组(CH组、EH组).第1～17天行生理盐水或石杉碱甲灌胃;第8 ～ 17天给予假电痉挛刺激或电痉挛刺激;第18天水迷宫定位航线实验;然后各组大鼠再随机分成2组,其中一组大鼠处死取海马用Western-Blot法检测P-ERK蛋白表达水平,另一组大鼠于48h后行水迷宫空间位置探寻实验.结果 电休克导致大鼠显著记忆障碍,P-ERK蛋白表达水平较假电休克对照组显著下降;而石杉碱甲干预的电休克大鼠记忆保持较好,P-ERK蛋白表达水平显著高于生理盐水干预的电休克大鼠,与假电休克大鼠相比差异无统计学意义.结论 石杉碱甲能减轻电休克模型大鼠记忆损害,其机制可能与海马P-ERK的表达增加有关.