AbstractBackgroundGut dysbiosis has been established as a characteristic of schizophrenia (SCH). However, the signatures regarding SCH patients with prominent negative symptoms (SCH‐N) in young adults have been poorly elucidated.MethodsStool samples were obtained from 30 young adults with SCH‐N, 32 SCH patients with prominent positive symptoms (SCH‐P) along with 36 healthy controls (HCs). Microbial diversity and composition were analyzed by 16S rRNA gene sequencing. Meanwhile, psychiatric symptoms were assessed by the positive and negative syndrome scale (PANSS).ResultsThere is a significant difference in β‐diversity but not α‐diversity indexes among the three groups. Moreover, we found a higher abundance of Fusobacteria and Proteobacteria phyla and a lower abundance of Firmicutes phyla in SCH‐N when compared with HC. Besides, we identified a diagnostic potential panel comprising six genera (Coprococcus, Monoglobus, Prevotellaceae_NK3B31_group, Escherichia‐Shigella, Dorea, and Butyricicoccus) that can distinguish SCH‐N from HC (area under the curve = 0.939). However, the difference in microbial composition between the SCH‐N and SCH‐P is much less than that between SCH‐N and the HC, and SCH‐N and SCH‐P cannot be effectively distinguished by gut microbiota.ConclusionThe composition of gut microbiota was changed in the patients with SCH‐N, which may help in further understanding of pathogenesis in young adults with SCH‐N.

Electroacupuncture (EA) is a neuroregulatory therapy for depression. Nonetheless, the effects of EA on the gut microbiome in mice models of depression are not well established. Here, using a chronic unpredictable mild stress (CUMS) model in mice, we evaluated the antidepressant effects of EA and changes in gut microbiota with behavioral tests and 16S rRNA gene sequencing. The results found that EA increased the time spent in the center area of the open-field test and the percentage of sucrose preference and reduced the immobility time in the tail suspension test in CUMS-treated mice. Furthermore, the genus Lachnoclostridium, Ruminococcaceae_UCG-002 and Rikenellaceae_RC9_gut_group were enriched in the CUMS group, which was positively correlated with depressive-like behaviors. Whereas phylum Actinobacteria and genus Allobaculum, Bifidobacterium, Dubosiella, Rikenella and Ileibacterium were enriched in the EA and CUMS + EA groups, all of which were negatively correlated with depressive-like behaviors. This study characterizes gut microbiota under EA treatment and provides new insights into the association of anti-depressive-like effects of EA and gut microbiota.

Background: Intestinal dysbacteriosis has frequently been involved in the context of depression. Nonetheless, only scant information is available about the features and functional changes of gut microbiota in female middle-aged depression (MAD). Objective: This study aims to explore whether there are characteristic changes in the gut microbes of female MAD and whether these changes are associated with depressive-like behaviors. Meanwhile, this study observed alterations in the lipid metabolism function of gut microbes and further examined changes in plasma medium- and long-chain fatty acids (MLCFAs) in mice that underwent fecal microbiota transplantation (FMT). Methods: Stool samples obtained from 31 MAD, along with 24 healthy individuals (HC) were analyzed by 16 S rRNA gene sequencing. Meanwhile, 14-month-old female C57BL/6J mice received antibiotic cocktails and then oral gavage of the microbiota suspension of MAD or HC for 3 weeks to reconstruct gut microbiota. The subsequent depressive-like behaviors, the composition of gut microbiota, as well as MLCFAs in the plasma were evaluated. Results: A noteworthy disruption in gut microbial composition in MAD individuals compared to HC was observed. Several distinct bacterial taxa, including Dorea, , Butyricicoccus, , and Blautia, , demonstrated associations with the demographic variables. A particular microbial panel encompassing 49 genera effectively differentiated MAD patients from HC (AUC = 0.82). Fecal microbiome transplantation from MAD subjects led to depressive-like behaviors and dysfunction of plasma MLCFAs in mice. Conclusions: These findings suggest that microbial dysbiosis is linked to the pathogenesis of MAD, and its role may be associated with the regulation of MLCFAs metabolism.

INTRODUCTION:Repetitive transcranial magnetic stimulation (rTMS) is a clinically useful therapy for depression. However, the effects of rTMS on the metabolism of fatty acids (FAs) and the composition of gut microbiota in depression are not well established.METHODS:Mice received rTMS (15 Hz, 1.26 T) for seven consecutive days after exposure to chronic unpredictable mild stress (CUMS). The subsequent depressive-like behaviors, the composition of gut microbiota of stool samples, as well as medium- and long-chain fatty acids (MLCFAs) in the plasma, prefrontal cortex (PFC), and hippocampus (HPC) were evaluated.RESULTS:CUMS induced remarkable changes in gut microbiotas and fatty acids, specifically in community diversity of gut microbiotas and PUFAs in the brain. 15 Hz rTMS treatment alleviates depressive-like behaviors and partially normalized CUMS induced alterations of microbiotas and MLCFAs, especially the abundance of Cyanobacteria, Actinobacteriota, and levels of polyunsaturated fatty acids (PUFAs) in the hippocampus and PFC.CONCLUSION:These findings revealed that the modulation of gut microbiotas and PUFAs metabolism might partly contribute to the antidepressant effect of rTMS.

Objective:To investigate the effect of early intervention with electroacupuncture (EA) on the gut microbiota in a mouse model of post-traumatic stress disorder(PTSD).Methods:Totally 32 C57BL/6 mice were randomly assigned to the following 4 groups ( n=8 for each group): Control group, EA group, PTSD group and PTSD+ EA group.After 7 days acclimation, mice in the PTSD group and PTSD+ EA group were subjected to modified single prolonged stress (mSPS). Mice in the EA group and PTSD+ EA group received EA (2/15 Hz, 1 mA, dilatational wave, 30 min/d) on "Baihui" for 7 days. Mice in the Control group and PTSD group received false stimulation (stimulated the same acupiont without electricity) for 7 days. Seven days after the last stimulation, elevated plus maze test and fear conditioning test were conducted to observe the effect of EA on PTSD-like behavior of mice. At the same time, feces of the mice were collected for gut microbiota detection by 16S rRNA sequencing.SPSS 19.0 was used for statistical analysis.One-way ANOVA was used for multiple group comparison and Bonferrani test was done for further pairwise comparision. Results:(1) There were statistically differences in the open arm activity time of the elevated plus maze test and the immobility time in contextual and cued fear conditioning test among the four groups ( F=6.93, 5.26, 14.51, all P<0.01). In the elevated plus maze test, mice in PTSD group ((60.17±15.52) s) showed significant less time in the open arms than mice in Control group((96.37±14.62) s) and PTSD+ EA group ((86.89±15.02) s) (both P<0.05). In the fear conditioning test, mice in PTSD group ((121.99±29.67) s, (130.82±29.11) s) showed significant increased immobility time both in contextual and cued fear conditioning tests than mice in Control group((74.50±26.65) s, (39.50±23.52) s) and PTSD+ EA group ((76.77±22.60) s, (102.17±3.39) s)(both P<0.05). (2) There were no significant differences among the four groups in the alpha diversity of gut microbiota ( F=0.79-2.45, all P>0.05). (3)Correlation analysis showed that 13 gut microbiotas were negatively correlated with the immobility time in contextual fear conditioning test, 2 gut microbiotas were positively correlated with it; 7 gut microbiotas were negatively correlated with the immobility time in cued fear conditioning test, 1 gut microbiota was positively correlated with it; 3 gut microbiotas were positively correlated with time spent in open arms of elevated plus maze test. Conclusion:Early intervention with EA can improve anxiety-fear like behaviors and gut microflora disorder in PTSD model mice.

IntroductionElectroacupuncture (EA) is a beneficial physiotherapy approach for addressing neuropsychiatric disorders. Nevertheless, the impact of EA on the gut microbiome in relation to anxiety disorders remains poorly understood.MethodsTo address this gap, we conducted a study using a chronic restraint stress (CRS) mouse model to investigate the anti-anxiety outcome of EA and its influence on gut microbiota. Our research involved behavioral tests and comprehensive sequencing of full-length 16S rRNA microbiomes.ResultsOur findings revealed that CRS led to significant anxiety-like behaviors and an imbalance in the gut microbiota. Specifically, we identified 13 species that exhibited changes associated with anxiety-like behaviors. Furthermore, EA partially alleviated both behaviors related to anxiety and the dysbiosis induced by CRS.DiscussionIn summary, this study sheds light on the alterations in gut microbiota species resulting from CRS treatment and brings new light into the connection between EA’s anti-anxiety effects and the gut microbiota.

Lipidomics has become a pivotal tool in biomarker discovery for the diagnosis of psychiatric illnesses. However, the composition and quantitative analysis of peripheral lipids in female patients with bipolar disorder (BD) have been poorly addressed. In this study, plasma samples from 24 female patients with BD and 30 healthy controls (HCs) were analyzed by comprehensive lipid profiling and quantitative validation based on liquid chromatography-mass spectrometry. Clinical characteristics and a correlation between the level of lipid molecules and clinical symptoms were also observed. We found that the quantitative alterations in several lipid classes, including acylcarnitine, lysophosphatidylethanolamine, GM2, sphingomyelin, GD2, triglyceride, monogalactosyldiacylglycerol, phosphatidylinositol phosphate, phosphatidylinositol 4,5-bisphosphate, phosphatidylethanolamine, phosphatidylserine, and lysophosphatidylinositol, were remarkably upregulated or downregulated in patients with BD and were positively or negatively correlated with the severity of psychotic, affective, or mania symptoms. Meanwhile, the composition of different carbon chain lengths and degrees of fatty acid saturation for these lipid classes in BD were also different from those of HCs. Moreover, 55 lipid molecules with significant differences and correlations with the clinical parameters were observed. Finally, a plasma biomarker set comprising nine lipids was identified, and an area under the curve of 0.994 was obtained between patients with BD and the HCs. In conclusion, this study provides a further understanding of abnormal lipid metabolism in the plasma and suggests that specific lipid species can be used as complementary biomarkers for the diagnosis of BD in women.

BACKGROUND:Neural oscillations play a role in the antidepressant effects of repetitive transcranial magnetic stimulation (rTMS). However, the effects of high-frequency rTMS on the neural oscillations of the medial prefrontal cortex (mPFC) and hippocampus (HPC) and its molecular mechanism have not been fully clarified.METHODS:The depressive-like behaviours, local field potentials (LFPs) of the ventral HPC (vHPC)-mPFC, and alternations of endocannabinoid system (ECS) in the HPC and mPFC were observed after rTMS treatment. Meanwhile, depressive-like behaviours and LFPs were also observed after cannabinoid type-1 receptor (CB1R) antagonist AM281 or monoacylglycerol lipase inhibitor JZL184 injection. Moreover, the antidepressant effect of rTMS was further assessed in glutamatergic-CB1R and gamma-amino butyric acid (GABA)-ergic -CB1R knockout mice.RESULTS:Alternations of endocannabinoids and energy value and synchronisation of mPFC-vHPC, especially the decrease of theta oscillation induced by CUMS, were alleviated by rTMS. JZL184 has similar effects to rTMS and AM281 blocked the effects of rTMS. GABAergic-CB1R deletion inhibited CUMS-induced depressive-like behaviours whereas Glutaminergic-CB1R deletion dampened the antidepressant effects of rTMS.LIMITATIONS:The immediate effect of rTMS on field-potential regulation was not observed. Moreover, the role of region-specific regulation of the ECS in the antidepressant effect of rTMS was unclear and the effects of cell-specific CB1R knockout on neuronal oscillations of the mPFC and vHPC should be further investigated.CONCLUSION:Endocannabinoid system mediated the antidepressant effects and was involved in the regulation of LFP in the vHPC-mPFC of high-frequency rTMS.

Background and Objectives: Lipidomics is a pivotal tool for investigating the pathogenesis of mental disorders. However, studies qualitatively and quantitatively analyzing peripheral lipids in adult patients with schizophrenia (SCZ) and major depressive disorder (MDD) are limited. Moreover, there are no studies comparing the lipid profiles in these patient populations. Materials and Method: Lipidomic data for plasma samples from sex- and age-matched patients with SCZ or MDD and healthy controls (HC) were obtained and analyzed by liquid chromatography-mass spectrometry (LC-MS). Results: We observed changes in lipid composition in patients with MDD and SCZ, with more significant alterations in those with SCZ. In addition, a potential diagnostic panel comprising 103 lipid species and another diagnostic panel comprising 111 lipid species could distinguish SCZ from HC (AUC = 0.953) or SCZ from MDD (AUC = 0.920) were identified, respectively. Conclusions: This study provides an increased understanding of dysfunctional lipid composition in the plasma of adult patients with SCZ or MDD, which may lay the foundation for identifying novel clinical diagnostic methods for these disorders.

Objective To investigate the impact of electroacupuncture on behavior and the gut microbiome in chronic unpredictable mild stress（CUMS） mouse model. Methods A total of 40 male C57BL/6mice were randomly distributed into control group, electroacupuncture group, CUMS group and treatment group（CUMS + electroacupuncture）, with 10 mice in each group. CUMS group and CUMS + electroacupuncture group accepted CUMS modeling. After the completion of modeling, mice in the control group and CUMS group were given sham stimulation for 7 days, and mice in the electroacupuncture group and CUMS + electroacupuncture group were given 2/15 Hz, 1.0 mA electroacupuncture stimulation for 7 days. 24 hours after the last intervention, feces were collected and stored at-80℃. Sugar preference test, open field test and forced swimming test were conducted on mice. 16S rDNA sequencing was performed on the feces of four groups of mice. α diversity, β diversity analysis and Linear Discriminant analysis Effect Size（LEfSe） were carried out by Operational Taxonomic Units（OTU） information. Spearman correlation analysis of the correlation between the behavioral indicators of mice and the enrichment levels of different bacterial populations. Results The time of exploring the open field center area of CUMS group mice was shorter than that of the control group [（22.058±4.148） s vs（37.864±4.407） s], the sugar preference rate was lower than that of the control group [（53.427±14.550）%vs（76.514±15.701）%], and the forced swimming immobility time was longer than that of the control group [（82.599±32.369） s vs（47.606±15.344） s], the difference was statistically significant（P＜0.01）. The time of exploring the open field center area of CUMS + electroacupuncture group mice was longer than that of the CUMS group [（30.604±6.060） s vs（22.058±4.148） s], the sugar preference rate was higher than that of the CUMS group [（72.731±13.933）% vs（53.427±14.550）%], and the forced swimming immobility time was shorter than that of the CUMS group [（53.633±17.933） s vs（82.599±32.369） s], the difference was statistically significant（P ＜ 0.05）. The number of OTU, ACE index and Chao index of intestinal flora in CUMS group were lower than those in the control group, and the difference was statistically significant（P ＜ 0.05）, but there was no statistical significance in the difference between CUMS + electroacupuncture group and CUMS group（P＞0.05）.Ruminococcaceae＿UCG-002, Lachnoclostridium and Rikenella ceae＿RC9＿gut＿group were abundant in the CUMS group, which were positively correlated with depressive-like behavior（P＜0.05）. Phylum Actinobacteria and genus Rikenella, Dubosiella, Ileibacterium, Bifidobacterium and Allobaculum were enriched in the electroacupuncture group and CUMS + electroacupuncture groups, all of which were negatively correlated with depressive-like behaviors. Conclusions Electroacupuncture treatment can ameliorate depressive-like behavior and regulate the composition of gut microbiota in CUMS-treated mice.

目的:探讨氟西汀对慢性不可预见应激(Chronic Unpredictable Mild Stress,CUS)模型大鼠海马内磷脂酰乙醇胺(phosphatidylethanolamine,PE)组成的影响.方法:(1)将24只SD大鼠随机分为对照组(Sham)、模型组(CUS)和氟西汀组(Flx).CUS组和Flx组均接受CUS造模,并且在造模后接受生理盐水(1 mL/kg)或氟西汀(10 mg/kg)腹腔注射,连续14天;Sham不进行CUS造模,但是每天接受腹腔注射生理盐水.随后处死大鼠,取海马进行脂质组学分析,比较各处理组海马总的PE和PE小分子相对丰度、不同碳链长度和含不同不饱和键PE的相对丰度差异.结果:(1)与CUS组相比,Sham组PE相对丰度明显减低,而Flx组明显增高(P＜0.05);(2)与Sham组相比,CUS组9个PE小分子相对丰度发生变化,PE(34∶1e)、PE(36∶1p)、PE(36∶2)、PE(36∶2p)、PE(36∶4)、PE(38∶2)、PE(38∶4)和 PE(40:7)共8个上调(P＜0.05或0.01),PE(34∶0p)下调(P＜0.05),CUS 组碳链长度为36的PE丰度上升(P＜0.05),碳链长度为38的PE丰度下降(P＜0.01),CUS组含0个不饱和键、4个不饱和键的PE丰度下调(P＜0.01,P＜0.05),而1个不饱和键的PE丰度上升(P＜0.05);(3)与CUS组相比,Flx组6个PE分子相对丰度减少,包括PE(34∶1e)、PE(36∶2)、PE(36∶4)、PE(38∶1p)、PE(38∶6e)和 PE(40∶5p)(P＜0.05或0.01),Flx 组碳链长度为34的 PE 丰度下降(P＜0.05),碳链长度为36的PE水平升高(P＜0.05),Flx组含1个不饱和键的PE丰度下调(P＜0.05),差异具有统计学意义.结论:氟西汀可以调节CUS模型大鼠海马的PE水平.

目的 探讨电针(EA)干预对创伤后应激障碍(PTSD)小鼠前额叶皮质(PFC)磷脂酰肌醇(PI)和溶血磷脂酰肌醇(LPI)的影响.方法 将24只雄性C57BL/6小鼠随机分为对照组、模型组(PTSD)和电针治疗组(EA+PTSD).经适应性饲养后,模型组和电针治疗组均接受单次延长应激造模,造模后在小鼠百会穴分别给予电针刺激或假电针刺激.在最后一次电针干预结束后7 d进行行为学检测,之后处死小鼠,取PFC进行脂质组学分析,比较各处理组PI和LPI含量的差异,并分析差异脂质分子与行为学的相关关系.结果 模型组开臂停留时间低于对照组和电针治疗组,模型组环境诱发僵直时间和声音诱发僵直时间高于对照组和电针治疗组(P<0.05).模型组LPI(18:1)、LPI(18:0)以及LPI总含量均低于对照组和电针治疗组(P<0.05);模型组PI(17:0/20:4)、PI(18:2/20:4)和PI(18:1/22:6)的含量均低于对照组(P<0.05),电针治疗组PI(17:0/20:4)、PI(16:0/20:4)和PI(18:1/20:4)的含量均低于对照组(P<0.05).LPI(18:1)含量与开臂停留时间呈正相关(P<0.01),与环境诱发僵直时间呈负相关(P<0.05);LPI(18:0)含量和LPI总含量均与开臂停留时间呈正相关(P<0.05).结论 PTSD模型小鼠前额叶皮质LPI水平降低,电针在缓解PTSD样行为的同时,也上调了其前额叶皮质的LPI水平.

The neuroprotective effect of electroacupuncture (EA) treatment has been well studied; growing evidence suggests that changes in lipid composition may be involved in the pathogenesis of post-traumatic stress disorder (PTSD) and may be a target for treatment. However, the influence of early EA intervention on brain lipid composition in patients with PTSD has never been investigated. Using a modified single prolonged stress (mSPS) model in mice, we assessed the anti-PTSD-like effects of early intervention using EA and evaluated changes in lipid composition in the hippocampus and prefrontal cortex (PFC) using a mass spectrometry-based lipidomic approach. mSPS induced changes in lipid composition in the hippocampus, notably in the content of sphingolipids, glycerolipids, and fatty acyls. These lipid changes were more robust than those observed in the PFC. Early intervention with EA after mSPS ameliorated PTSD-like behaviors and partly normalized mSPS-induced lipid changes, notably in the hippocampus. Cumulatively, our data suggest that EA may reverse mSPS-induced PTSD-like behaviors due to region-specific regulation of the brain lipidome, providing new insights into the therapeutic mechanism of EA.

BACKGROUND:The association between abnormal gut microbiome composition and depression is well established. However, the composition and functional capacity of the gut microbiota regarding depressed women has been poorly addressed.METHODS:Stool samples from 62 female patients with major depressive disorder (MDD) and 46 healthy controls (Con) were analyzed by 16S rRNA gene sequencing; Twenty fecal samples from the patient group and 21 fecal samples from the Con group were further analyzed by shotgun metagenomic sequencing. Psychiatric symptoms and psychological, social, and professional functioning was also assessed.RESULTS:Phylum Bacteroidetes, proteobaeteria, and Fusobacteria were greatly enriched in patients with MDD, while the Firmicutes and Actinobacteria phyla were consistently higher in Con. Notably, 18 microbial markers were identified on a random forest model and achieve an area under the curve of 0.92 between patients with MDD and the Con group. Forty-five species and their associated function were identified with statistically significant differences between patients with MDD and the Con group.LIMITATIONS:The number of recruited samples, especially samples enrolled for shotgun metagenomic sequencing was relatively small, and the stool samples were collected only at baseline, making it difficult to establish a causal association between changes in gut microbiota compositions and disease remission.CONCLUSIONS:This study characterizes the gut microbiota and their related function in female MDD. The gut microbiota-based biomarkers may be helpful in diagnosis and the altered gut microbial metabolites may contribute to the pathogenesis of MDD in women, representing potential microbial targets.

目的:通过shRNA抑制沉默信息调节因子1(sirtuin 1,Sirt1)基因表达,研究Sirt1在高压氧预处理改善异氟醚(isoflurane,ISO)诱导小鼠认知功能障碍中的作用及其对小鼠海马BDNF、GDNF基因表达的影响.方法:将64只C57雄性小鼠随机分为假手术组(Sham组)、高压氧组(HBO组)、异氟醚组(ISO组)、高压氧预处理+异氟醚组(HBO+ ISO组);以及对照组(NS组)、Sirtl抑制组(sh-Sirt1组)、对照+高压氧预处理组(NS+ HBO组)和Sirt1抑制+高压氧预处理组(sh-Sirt1+ HBO组),每组8只.经慢病毒转染以及ISO末次暴露24小时后进行认知功能测试(Morris水迷宫测试),随后处死小鼠,利用实时荧光定量聚合酶链反应(RT-qPCR)检测海马BDNF和GDNF的mRNA表达情况.结果:(1)异氟醚可以导致明显的认知功能障碍,与Sham组相比,ISO组靶象限探索时间百分比显著减低(P＜0.01),ISO组小鼠海马BDNF和GDNF mRNA表达水平显著下降(P＜0.01).(2)高压氧预处理可以改善POCD小鼠的认知功能障碍,ISO+ HBO组靶象限探索时间百分比显著高于ISO组(P＜0.05),ISO+ HBO组小鼠海马BDNF(P＜0.05)和GDNF (P＜0.01)mRNA表达水平显著升高.(3)高压氧预处理可以显著增加POCD小鼠海马BDNF(P＜0.01)和GDNF(P＜0.05)mRNA表达水平,慢病毒介导shRNA靶向下调Sirt1可以逆转高压氧预处理对POCD小鼠海马BD-NF(P＜0.05)和GDNF(P＜0.01)mRNA表达水平的改变.结论:高压氧预处理是治疗POCD的有效方法,Sirt1可能是POCD治疗的潜在分子靶点.

目的:探讨高压氧预处理(Hyperbaric oxygen preconditioning,HBO-PC)对大鼠脑缺血再灌注损伤的保护作用及对其海马脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)、胶质细胞源性神经营养因子(glialcellline-derivedneurotrophicfactor,GDNF)基因表达的影响.方法:将32只SD雄性大鼠随机分为对照组(Sham组)、高压氧对照组(HBO组)、模型组(MCAO组)、高压氧预处理+模型组(HBO+ MCAO组),对HBO组和HBO+ MCAO组连续给予高压氧预处理5天,随后对MCAO组和HBO +MCAO组进行右侧颈内动脉栓线术,建立大脑中动脉闭塞(middle cerebral artery occlusion,MCAO)模型,其他两组行假手术,于术后第7天对各组大鼠进行Morris水迷宫行为学检测和神经功能评分,检测结束后处死大鼠,进行神经功能缺损评分及氯化三苯基四氮唑(2,3,5-triphenyltetrazolium chloride,TTC)染色;通过蛋白免疫印迹法(Western Blot)检测大鼠海马组织BDNF和GDNF的基因表达情况.结果:(1)神经功能评分提示:Sham组和HBO组均未出现神经功能障碍,MCAO组大鼠出现明显的神经功能障碍,MCAO+ HBO组神经功能评分明显高于MCAO组(P＜0.05).(2)TTC检测提示:Sham组和HBO组脑组织损伤一侧均未出现梗死灶,MCAO组出现较大的梗死面积比(25.45+8.75)％,MCAO+HBO组的梗死面积比(18.84±10.55)显著小于MCAO组,差异具有统计学意义(P＜0.05).(3)Western Blot检测显示:MCAO组BDNF与GDNF基因表达水平显著低于Sham组和HBO组,差异具有统计学意义(P＜0.05),而MCAO+HBO组可以逆转这一效应,差异具有统计学意义(P＜0.05).结论:高压氧预处理可以通过调节BDNF、GDNF基因表达,改善MCAO模型大鼠神经功能和认知水平,发挥神经保护作用.

目的 探讨高压氧早期干预对创伤后应激障碍(PTSD)模型大鼠行及海马核因子E2相关因子2(nuclear factor erythroid 2-related factor 2,Nrf2)及血红素加氧酶1(HO-1)基因表达的影响.方法 将32只雄性Sprague-Dawley大鼠随机分为对照组(sham组)、高压氧组(HBO组)、模型组(ESPS组)、模型+高压氧早期干预组(ESPS+HBO组),每组8只.ESPS组和ESPS+HBO组大鼠经增强型单次延长应激(ESPS)构建PTSD模型,其他两组不接受ESPS造模,但置于同一实验室环境.造模结束24 h后,各组大鼠置于高压氧舱进行1 h高压氧(2.5个大气压,100％O2)或常压空气干预,连续5 d.干预结束后将大鼠放回原饲养笼中不受打扰饲养7 d.通过旷场实验、高架十字迷宫实验以及条件性恐惧性实验观察大鼠的行为表现,并通过蛋白免疫印迹法(Western Blot)检测大鼠海马组织Nrf2和HO-1的表达情况.结果 (1)各处理组旷场内总运动距离的差异无统计学意义(P>0.05);ESPS组中心区运动时间[(20.52±9.25)s]和进入旷场中心区次数[(15.22±4.38)次]均显著低于sham组[(44.94±14.49)s、(32.77±6.22)次],而ESPS+HBO组[(35.49±13.04)s、(21.50±5.98)次]则显著高于ESPS组(均P<0.05).(2)与sham组开臂停留时间[(54.47±23.23)s]、开臂停留时间百分比[(17.91±8.11)％]和进入开臂次数[(10.54±3.85)次]比较,ESPS组各指标[(26.18±8.56)s]、[(7.23±4.24)％]和[(3.10±1.96)次]均显著降低,而ESPS+HBO组各指标[(40.77±16.66)s]、[(13.66±8.81)％]和[(6.40±1.71)次]均显著高于ESPS组(均P<0.05).(3)ESPS组环境诱发僵直时间[(183.21±25.83)s]和声音诱发僵直时间[(202.03±47.79)s]均显著高于sham组和ESPS+HBO组(均P<0.05).(4)ESPS组海马Nrf2(0.23±0.08)和HO-1(0.84±0.13)的蛋白相对表达水平均显著低于sham组和ESPS+HBO组(均P<0.05).(5)sham组与HBO组在上述行为和分子表达指标之间的差异均无统计学意义(均P>0.05).结论 高压氧早期干预可能通过调节海马的抗氧化系统Nrf2/HO-1的表达水平改善PTSD大鼠的焦虑样行为和认知损伤.

The antipsychotic effect of Quetiapine (Que) has been extensively studied and growing evidence suggests that Que has a beneficial effect, improving cognitive functions and promoting myelin repair. However, the effects of Que on the brain lipidome and the association between Que-associated cognitive improvement and changes in lipids remain elusive. In the present study, we assessed the cognitive protective effects of Que treatment and used a mass spectrometry-based lipidomic approach to evaluated changes in lipid composition in the hippocampus, prefrontal cortex (PFC), and striatum in a mouse model of cuprizone (CPZ)-induced demyelination. CPZ induces cognitive impairment and remarkable lipid changes in the brain, specifically in lipid species of glycerophospholipids and sphingolipids. Moreover, the changes in lipid classes of the PFC were more extensive than those observed in the hippocampus and striatum. Notably, Que treatment ameliorated cuprizone-induced cognitive impairment and partly normalized CPZ-induced lipid changes. Taken together, our data suggest that Que may rescue cognitive behavioral changes from CPZ-induced demyelination through modulation of the brain lipidome, providing new insights into the pharmacological mechanism of Que for schizophrenia.

目的 探讨高压氧预处理对异氟醚(ISO)所致中年小鼠认知障碍的改善作用及海马脑源性神经营养因子(BDNF)和胶质细胞源性神经营养因子(GDNF)蛋白表达和mRNA水平的影响.方法 将32只8月龄雄性C57BL/6J小鼠按随机数字表随机分为对照组(sham组)、高压氧组(HBO组)、异氟醚组(ISO组)和高压氧预处理+异氟醚组(HBO+ISO组),每组8只.HBO组和ESPS+HBO组小鼠置于高压氧舱进行1 h高压氧(2.5个大气压,100％O2)干预,对照组小鼠常压空气干预(模拟除压力和氧浓度以外的其他过程和环境条件)1 h,均连续5 d.在第3天HBO或常压空气干预结束后2 h,各组小鼠进行水迷宫训练,连续3 d.最后1次水迷宫训练后24 h,ISO组和HBO+ISO组小鼠经异氟醚吸入麻醉构建认知障碍模型,其他2组吸入对照气体.24 h后进行水迷宫检测认知功能,并通过蛋白免疫印迹(Western Blot)和实时定量聚合酶链式反应(RT-PCR)检测小鼠海马BDNF和GDNF蛋白表达和mRNA水平的变化.结果?(1)各处理组水迷宫总运动距离和平均运动速度的差异均无统计学意义(均P>0.05);ISO组目标象限停留时间百分比为(26.74±10.52)％,显著低于sham组[(48.33±9.18)％,P<0.01],而HBO+ISO组[(39.06±8.39)％]则显著高于ISO组(P<0.05).(2)ISO组海马BDNF(0.56±0.09)和GDNF(0.52±0.10)的蛋白相对表达水平均显著低于sham组和HBO+ISO组(均P<0.01或0.05).(3)ISO组海马BDNF(0.51±0.08)和GDNF(0.25±0.09)的mRNA相对水平也均显著低于sham组和HBO+ISO组(均P<0.01).(4)sham组与HBO组在上述行为和分子水平之间的差异均无统计学意义(均P>0.05).结论 高压氧预处理可能通过调节海马的BDNF和GDNF表达水平,改善异氟醚所致认知损伤.

The antidepressant effect of repetitive transcranial magnetic stimulation (rTMS) has been extensively studied; growing evidence suggests that changes in lipid composition may be involved in the pathogenesis of depression and may be a targeted mechanism for treatment. However, the influence of rTMS on lipid composition and the differences between these effects compared to antidepressants like fluoxetine (Flx) have never been investigated. Using a chronic unpredictable stress (CUS) model in rats, we assessed the antidepressive effects of rTMS and Flx treatments and evaluated changes in lipid composition in the hippocampus and prefrontal cortex (PFC) using a mass spectrometry-based lipidomic approach. Both rTMS and Flx treatments ameliorated depressive-like behaviors induced by CUS. Moreover, changes in lipid composition, especially glycerophospholipids, sphingolipids, and glycerolipids induced by CUS in the hippocampus were more robust than those observed in the PFC. CUS led to decreased levels of 20 carbon-containing fatty acyls and polyunsaturated fatty acyls in the PFC, and decreased levels of acyl carnitines (AcCa) in both the hippocampus and PFC. Notably, rTMS treatment had higher impact than Flx on composition of glycerophospholipids and sphingolipids in the hippocampus that were altered by CUS, while Flx attenuated CUS-induced changes in the PFC to a greater extent than rTMS. However, neither was able to restore fatty acyls and AcCa to baseline levels. Altogether, modulation of the brain lipidome may be involved in the antidepressant action of rTMS and Flx, and the degree to which these treatments induce changes in lipid composition within the hippocampus and PFC might explain their differential antidepressant effects.