High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) is an effective treatment for depression, but its synaptic mechanisms remain incompletely understood. Using a chronic unpredictable mild stress (CUMS) mouse model, we investigated whether cannabinoid receptor 1 (CB1R) signaling in distinct neuronal populations contributes to the amelioration of depressive-like behaviors by HF-rTMS through modulation of prefrontal inhibitory synaptic transmission. Behavioral assessments were combined with whole-cell patch-clamp recordings of spontaneous inhibitory postsynaptic currents (sIPSC) in prefrontal cortex pyramidal neurons, along with systemic pharmacological CB1R blockade (AM281) and conditional knockout mice with deletion of CB1R in glutamatergic (vGlut1-CB1R-KO) or GABAergic (GAD2-CB1R-KO) neuronal populations. sIPSC frequency and amplitude were analyzed as indirect indices of presynaptic release and postsynaptic receptor function, respectively. HF-rTMS ameliorated CUMS-induced depressive-like behaviors and partially normalized sIPSC alterations (frequency and amplitude), which were attenuated by AM281. In vGlut1-CB1R-KO mice, baseline sIPSC frequency was reduced and half-width prolonged; CUMS exacerbated these alterations and induced anhedonia/anxiety, yet HF-rTMS failed to rescue any behavioral or synaptic changes. In contrast, GAD2-CB1R-KO mice exhibited baseline anxiety-like behavior accompanied by increased sIPSC frequency, consistent with loss of presynaptic CB1R-mediated suppression of GABA release, but showed attenuated-CUMS-induced depressive-like behaviors,; HF-rTMS partially modulated postsynaptic function (increased amplitude, accelerated kinetics). These findings suggest that glutamatergic CB1R signaling contributes to the ability of HF-rTMS to modulate presynaptic inhibitory function. Meanwhile, GABAergic CB1R ablation is accompanied by reduced behavioral vulnerability to chronic stress and may shift HF-rTMS actions toward potential postsynaptic modulatory processes. Collectively, these observations implicate cell-type-specific CB1R signaling in shaping the synaptic responses of prefrontal inhibitory circuits to HF-rTMS.

Background Although the relationship between negative symptoms and cognitive deficits in schizophrenia has been extensively investigated, there remained limited research on the differential clinical factors influencing cognitive function in chronic schizophrenia patients with distinct symptom profiles. This study aimed to investigate the clinical correlates of cognitive dysfunction in chronic schizophrenia patients categorized by predominant symptom manifestations. Methods In this cross-sectional study, 409 Chinese patients with chronic schizophrenia underwent comprehensive assessment using the following standardized instruments: the Positive and Negative Syndrome Scale (PANSS), the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), the Insomnia Severity Index (ISI), and the Global Deterioration Scale (GDS). Sociodemographic data were also collected. Results Patients with prominent negative symptoms (SCZ-N) had significantly lower RBANS total scores compared to those with dominant positive symptom (SCZ-P). Spearman’s correlation analysis revealed that in the SCZ-N group, PANSS total score and negative symptom score were significantly negatively correlated with RBANS total score and all 5 subdomain scores (all p < 0.01). In contrast, in the SCZ-P group, significant negative correlations were mainly observed between PANSS score, negative symptom score, RBANS total score and attention score (all p < 0.01). Multiple linear regression analysis further showed that cognitive impairment was associated with multiple factors, including years of education, gender, illness duration, PANSS general psychopathology score, and GDS assessment levels in the SCZ-N group. In the SCZ-P group, cognitive dysfunction was primarily associated with GDS assessment levels and negative symptom score. Conclusions The findings of this study indicate that the severity of negative symptoms is a strong correlate of cognitive impairment in patients with chronic schizophrenia. These results collectively indicate that targeting negative symptoms is paramount for effective cognitive management in chronic schizophrenia.

ABSTRACT Purpose Repetitive transcranial magnetic stimulation (rTMS) represents a potential clinical tool in treating bipolar disorder (BD). However, the intervention of rTMS combined with pharmacotherapy on the plasma fatty acids (FAs) in patients with bipolar depression has not been reported yet. Method In this study, we assessed the clinical symptoms and evaluated plasma FAs from 30 inpatients with bipolar depression at baseline phase (BD group), after 2 weeks of treatment with rTMS combined with quetiapine and mood stabilizer (BD‐2w group), and 32 healthy controls (HCs). Finding We found that acetic acid, propionic acid, isovaleric acid, isobutyric acid, and valeric acid, as well as levels of total short‐chain fatty acids (SCFAs), were decreased in both BD and BD‐2w groups, and levels of several medium‐ and long‐chain fatty acids (MLCFAs) were altered in BD when compared with HC. Moreover, 2 weeks of treatment increased the levels of various MLCFAs. Finally, we developed combinational FAs panels that could distinguish BD from HC (area under the curve [AUC] = 0.961), BD‐2w from HC (AUC = 0.978), and BD from BD‐2w (AUC = 0.891) effectively. Conclusion These findings might provide a basis for developing diagnostic methods and reveal the potential relationship between bipolar depression and plasma FAs.

BACKGROUND:Intestinal dysbacteriosis is frequently implicated in generalized anxiety disorder (GAD). However, the molecular mechanisms and functional changes of the gut-brain axis in GAD remain largely unexplored. METHODS:We investigated anxiety-like behaviors, gut microbiota changes, brain region-specific endocannabinoid (eCB) system alterations, including the expression of cannabinoid type 1 (CB1R), monoacylglycerol lipase (MAGL), and fatty acid amide hydrolase (FAAH) in the hippocampus (Hip), prefrontal cortex (PFC), and amygdala (Amy), as well as plasma medium- and long-chain fatty acids (MLCFAs) in a mouse model of chronic restraint stress (CRS) and antibiotic-treated mice receiving fecal microbiota transplantation from GAD patients (FMT-GAD). Additionally, we assessed the impact of FMT-GAD on anxiety-like behavior in systemic CB1R/FAAH/MAGL knockout mice. RESULTS:CRS induced anxiety-like behaviors, suppressed eCB signaling in the brain, and altered the gut microbiota and plasma MLCFA composition in mice. FMT-GAD-treated mice exhibited anxiety-like behaviors, increased FAAH expression in the Hip and Amy, and MAGL expression in the Hip, while reducing CB1R expression in the Hip. FMT-GAD was associated with decreased plasma polyunsaturated fatty acids (PUFAs) and reduced microbiome function for fatty acid biosynthesis. Notably, FMT-GAD intensified anxiety-like behaviors in CB1R-KO mice but failed to induce anxiety-like behaviors in MAGL-KO and FAAH-KO mice. CONCLUSIONS:This study demonstrates that the interplay between the gut microbiota and the eCB system modulates GAD-related anxiety-like behaviors.

OBJECTIVE:This study investigated the role of endocannabinoid (eCB) signaling in anxiety-like behaviors associated with a PTSD mouse model (SPS&S), focusing on oxidative stress and inflammation. METHODS:We examined expression of eCB-related proteins (Cannabinoid receptor type 1, CB1 Receptor; NAPE-specific phospholipase D, NAPE-PLD; Fatty acid amide hydrolase, FAAH; and Monoacylglycerol lipase, MAGL) and inflammatory markers (IL-1β, caspase-1) in the mPFC, hippocampus, and amygdala of SPS&S-exposed mice. Plasma oxidative stress markers (MDA, SOD, ROS) and cytokines (IL-1β, IL-6, TNF-α, COX-2) were measured by ELISA. The CB1 receptor agonist WIN 55,212-2 or vehicle was administered systemically, then anxiety-like behaviors and conditioned fear were assessed. RESULTS:SPS&S exposure induced significant anxiety-like behaviors and increased freezing in fear tests. It decreased CB1 receptor and NAPE-PLD expression while increasing FAAH and MAGL levels in all examined brain regions, alongside elevated IL-1β and caspase-1. Plasma oxidative stress and inflammatory cytokines were also elevated. WIN 55,212-2 administration mitigated anxiety-like behaviors but not conditioned fear responses. Crucially, it normalized the elevated plasma oxidative stress and inflammatory cytokine levels. CONCLUSION:SPS&S disrupts eCB signaling and increases neuroinflammation and peripheral oxidative stress/inflammation. Activation of CB1 receptor alleviates PTSD-associated anxiety-like behaviors and normalizes peripheral oxidative/inflammatory biomarkers, highlighting the critical involvement of eCB-related oxidative stress and inflammatory pathways. Targeting the eCB system represents a potential therapeutic strategy for anxiety symptoms in PTSD.

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.

Mounting evidence has identified the rapid and sustained antidepressive and anxiolytic-like effects of esketamine. However, the underlying mechanism of this no-monoamine target rapid-onset antidepressant is still underexplored. Immune-inflammatory pathways and cell-mediated immune activation, mainly including inflammatory cytokines in plasma, play a pivotal role in the pathogenesis of major depressive disorder and are also a potential therapeutic target for MDD. The current study was designed to clarify the role of esketamine on the expression of plasma cytokines in a depressive-like model introduced by chronic variable stress (CVS). In this study, a 21-day consecutive CVS protocol was applied to produce depressive- and anxiety-like behaviors. After the single dose or 7-day repeated administration of esketamine or fluoxetine, the depressive- and anxiety-like behaviors and the expression of inflammatory cytokines in plasma were examined. Both a single dose of esketamine and 7-days repeated fluoxetine administration elicited anti-depressive and anxiolytic effects in mice exposed to CVS. Additionally, CVS produced significant changes in the plasma inflammatory factors, notably increasing the expression of IL-1β, IL-6, IL-8, IL-17A, TNFα, IL-4, IL-9, IL-24, IL-37, IFN-β, and CXCL12, while reducing IL-10 and IL-33. With the administration of esketamine and fluoxetine, CVS-produced inflammatory disturbances were partially normalized. Together, our findings provide a novel insight that acute esketamine treatment could rescue CVS-produced depressive-like and anxiety-like behaviors in mice by normalizing the expression of inflammatory cytokines; this effect was similar to the repeated administration of fluoxetine. These results contributed to the understating of rapid anti-depressant effects elicited by esketamine.

抑郁症是危害人类健康的主要精神疾病之一.现有的单胺类假说并不能完全解释抑郁症的发病机制,以此为靶点的抗抑郁药物起效速度慢、部分患者缺乏疗效.线粒体是存在于真核细胞中的多功能细胞器,在能量产生、细胞凋亡、氧化应激、神经发生等过程中发挥关键作用.近年来,大量的证据表明线粒体功能障碍和抑郁症发病机制关系密切.在本文中,我们对线粒体能量代谢障碍与抑郁症关系的研究进展进行综述,包括线粒体DNA损伤、线粒体和炎症及神经发生之间的关联、线粒体靶向治疗抑郁症的潜能等,并总结了现有抗抑郁治疗与线粒体功能调控相关的进展,从而为深入理解抑郁症发病机制以及筛选靶向线粒体的新型治疗策略提供参考.

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.

IntroductionThis study aimed to identify the effect of electroacupuncture (EA) treatment on post-stroke depression (PSD) and explore whether cannabinoid receptor 1 (CB1R)-mediated mitochondrial biogenesis accounts for the treatment effect of EA.MethodsThe PSD mouse model was induced by a consecutive 14-day chronic unpredictable stress operation after 7 days of recovery from the bilateral common carotid artery occlusion surgery. Either EA treatment or sham stimulation was performed for 14 consecutive days from Day 7 after the BCCAO operation. Subjects’ PSD-like behaviors were tested via open field test, sucrose preference test, novelty suppressed feeding test, tail suspension test, and forced swim test, and subjects’ cognitive function was examined using Y-maze and novelty object recognition test. In addition, the levels of CB1R, mitochondrial biogenesis-related proteins (nuclear transcription factor 1, NRF1; mitochondrial transcription factor A, TFAM), proteins related to mitochondrial function (Cytochrome C, Cyto C; AIF, COX IV), and mitochondrial DNA were measured. To elucidate the role of CB1R in EA treatment, CB1R antagonists AM251 and CB1R-shRNA were given to mice before EA treatment. Likewise, subjects’ depressive-like behaviors, cognitive function, mitochondrial function, and mitochondrial biogenesis were examined after the PSD procedure.ResultsIt has been showed that EA successfully ameliorated depressive-like behaviors, improved cognitive dysfunctions, and upregulated CB1R, NRF1 and TFAM expressions. However, the supplementation of AM251 and CB1R-shRNA blocked the antidepressant-like effects generated by EA, and EA failed to improve cognitive dysfunction, upregulate CB1R protein expression, and increase mitochondrial function and biogenesis.ConclusionAltogether, these results indicated that EA ameliorated PSD-like behaviors in mice, improved cognitive dysfunctions after PSD, and promoted mitochondrial biogenesis by activating CB1R, a novel mechanism underlying EA’s antidepressant-like effects in treating PSD.

Background and Objectives: Disturbance of tryptophan (Trp) and fatty acid (FA) metabolism plays a role in the pathogenesis of psychiatric disorders. However, quantitative analysis and comparison of plasma Trp metabolites and medium- and long-chain fatty acids (MCFAs and LCFAs) in adult patients with major depressive disorder (MDD) and schizophrenia (SCH) are limited. Materials and Methods: Clinical symptoms were assessed and the level of Trp metabolites and MCFAs and LCFAs for plasma samples from patients with MDD (n = 24) or SCH (n = 22) and healthy controls (HC, n = 23) were obtained and analyzed. Results: We observed changes in Trp metabolites and MCFAs and LCFAs with MDD and SCH and found that Trp and its metabolites, such as N-formyl-kynurenine (NKY), 5-hydroxyindole-3-acetic acid (5-HIAA), and indole, as well as omega-3 polyunsaturated fatty acids (N3) and the ratio of N3 to omega-6 polyunsaturated fatty acids (N3: N6), decreased in both MDD and SCH patients. Meanwhile, levels of saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA) decreased in SCH patients, and there was a significant difference in the composition of MCFAs and LCFAs between MDD and SCH patients. Moreover, the top 10 differential molecules could distinguish the two groups of diseases from HC and each other with high reliability. Conclusions: This study provides a further understanding of dysfunctional Trp and FA metabolism in adult patients with SCH or MDD and might develop combinatorial classifiers to distinguish between these disorders.

目的 探讨艾司氯胺酮对慢性可变应激(CVS)小鼠抑郁样行为及前额叶皮质(PFC)鞘脂水平的影响.方法 将31只C57小鼠随机分为对照组(n=10)、模型+生理盐水组(n=10)和模型+艾司氯胺酮治疗组(n=11).模型+生理盐水组和模型+艾司氯胺酮治疗组小鼠均接受21 d CVS造模.造模结束后,两组小鼠分别接受10 μL/g生理盐水、10mg/kg艾司氯胺酮腹腔注射.通过旷场实验、高架十字迷宫测试、悬尾实验及强迫游泳实验测试小鼠的抑郁样行为;随后处死小鼠,分离出PFC,通过高效液相色谱-质谱联用技术检测PFC鞘脂水平及组成小分子差异,采用LipidSearch 4.1和SIMCA-P 14.1软件分析脂质相对含量.使用SPSS 26.0进行数据处理,多组间差异采用单因素方差分析,两组间差异进行Tukey检验.结果 ①CVS模型可以诱导稳定的小鼠抑郁样行为,3组小鼠旷场测试、高架十字迷宫测试、悬尾实验及强迫游泳测试的结果均有统计学差异;单次腹腔注射艾司氯胺酮可以逆转小鼠抑郁样行为,并且改变部分鞘脂水平及其组成小分子.②3组小鼠鞘脂总体水平的差异有统计学意义(F2.28=22.92,P＜0.01),鞘脂的三个亚类鞘磷脂(F2.28=15.76,P＜0.01)、脑苷脂(F2,28=21.56,P＜0.01)、神经节苷脂(F2,28=4.056,P＜0.05)之间的差异均有统计学意义.进一步对其小分子组成进行分析发现,CVS造模之后植物鞘氨醇(phSM)、GM3均明显下降,艾司氯胺酮治疗增加了上述脂质小分子的水平(均P＜0.05);与对照组相比,模型+生理盐水组磷酸肌酸(CerP)、硫苷脂水平下降,而艾司氯胺酮治疗并未影响上述脂质小分子的水平.③PFC鞘脂水平与行为学结果之间存在一定的相关性.CVS小鼠PFC总体鞘脂水平与旷场中心停留时间存在相关性(Pearson r=0.378 1,P＜0.05),小分子phSM与旷场中心停留时间存在相关性(P＜0.05);CVS小鼠PFC脑苷脂的小分子神经酰胺、CerP和CerG3水平与悬尾不动时间存在相关性(均P＜0.05).结论 艾司氯胺酮治疗可以改善CVS小鼠抑郁样行为,其作用可能与小鼠PFC鞘脂相对含量变化,尤其是鞘磷脂水平相关.

青少年抑郁症是指发生在未成年时期,以显著而持续的情绪低落、快感缺失为主要表现的一类精神疾病.青少年抑郁症严重损害患者社会认知功能,并增加自杀风险.目前青少年抑郁症的发病机制仍不清楚,且缺乏针对青少年抑郁症的可靠治疗药物.青少年抑郁症临床特点包括了更严重的社交回避、高发的非自杀性自伤行为和自杀意念等,而上述症状与奖赏环路功能异常密切相关.因此,奖赏环路功能异常可能是青少年抑郁的重要发病机制.本文将回顾青少年奖赏环路特征发育及其功能异常在青少年抑郁症中的作用机制最新进展,从而为未来青少年抑郁症发病机制研究及筛选有效的青少年抑郁症治疗措施提供理论根据.

Introduction: Compelling evidence indicates that a single sub-anesthetic dose of (S)-ketamine elicits rapid and robust antidepressant effects. However, the underlying mechanisms behind the antidepressant effects of (S)-ketamine remain unclear. Methods: Here, using a chronic variable stress (CVS) model in mice, we analyzed changes inthe lipid compositions of the hippocampus and prefrontal cortex (PFC) with a mass spectrometry-based lipidomic approach. Results: Similar to previous research outcomes, the current study also showed that (S)-ketamine reversed depressive-like behaviors in mice produced by CVS procedures. Moreover, CVS induced changes inthe lipid compositions of the hippocampus and PFC, notably in the contents of sphingolipids, glycerolipids, and fatty acyls. With the administration of (S)-ketamine, CVS-induced lipid disturbances were partially normalized, particularly in the hippocampus. Conclusion: Altogether, our results indicated that (S)-ketamine could rescue CVS-induced depressive-like behaviors in mice through region-specific modulation of the brain lipidome, contributing to the understanding of (S)-ketamine's antidepressant effects.

目的 观察青年和老年小鼠吸入异氟醚后对学习记忆、海马线粒体、突触以及神经元树突形态的影响.方法 青年(6月龄)及老年(18月龄)雄性C57BL/6小鼠各20只,随机分为4组(n=10):青年组、青年吸醚组、老年组和老年吸醚组.青年组和老年组均吸入1 000 mL/L O2 2 h,青年吸醚组和老年吸醚组均吸入15 mL/L异氟醚气体2h;通过新奇物体识别测试观察小鼠的行为表现,评估其学习记忆能力;使用透射电镜技术观察小鼠海马线粒体和突触的区域分布及超微结构;利用高尔基染色观察海马神经元树突形态变化.结果 ①与青年组相比,老年组对新物体的探索率降低(P＜0.05),树突棘数量减少(P＜0.01),线粒体面积增大(P＜0.05),线粒体密度降低(P＜0.01),突触数量减少且结构模糊.②与青年组相比,青年吸醚组对新物体的探索率减少(P＜0.05),树突长度变短(P＜0.05),树突分支数量减少(P＜0.01),线粒体面积增大(P＜0.01),突触结构被破坏;与老年组相比,老年吸醚组的新物体探索率降低(P＜0.01),树突长度、分支和树突棘数量均发生显著性下调(均P＜0.05),线粒体面积增大、密度降低(P＜0.05),突触结构受损严重.③与青年吸醚组相比,老年吸醚组的新物体探索率降低(P＜0.01),树突长度减小(P＜0.05),树突棘减少(P＜0.01),线粒体面积增大(P＜0.05),密度降低(P＜0.01),突触小泡受损严重,突触数量较少.结论 异氟醚会造成小鼠学习记忆功能下降,表现为海马神经元树突形态改变、线粒体和突触受损,并且这种损伤对老年小鼠更为严重.

Lipidomics has been established as a potential tool for the investigation of mental diseases. However, the composition analysis and the comparison of the peripheral lipids regarding adult women with major depressive depression (MDD) or bipolar depression (BPD) has been poorly addressed. In the present study, age-matched female individuals with MDD (n = 28), BPD (n = 22) and healthy controls (HC, n = 25) were enrolled. Clinical symptoms were assessed and the plasma samples were analyzed by comprehensive lipid profiling based on liquid chromatography-mass spectrometry (LC/MS). We found that the composition of lipids was remarkably changed in the patients with MDD and BPD when compared to HC or compared to each other. Moreover, we identified diagnostic potential biomarkers comprising 20 lipids that can distinguish MDD from HC (area under the curve, AUC = 0.897) and 8 lipids that can distinguish BPD from HC (AUC = 0.784), as well as 13 lipids were identified to distinguish MDD from BPD with moderate reliability (AUC = 0.860). This study provides further understanding of abnormal lipid metabolism in adult women with MDD and BPD and may develop lipid classifiers able to effectively discriminate MDD from BPD and HC.

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.