Do different types of stress differentially alter behavioural and neurobiological outcomes associated with depression in rodent models? A systematic review

Cataloguing the effects of different types of stress on behaviour and physiology in rodent models has not been comprehensively attempted. Here, we systematically review whether chronic exposure to physical stress, psychosocial stress, or both types of stress can induce different behavioural and neurobiological outcomes in male and female rodents. We found that physical stress consistently increased depressive-like behaviour, impaired social interaction and decreased body weight, while psychosocial stress consistently increased both anxiety- and depressive-like behaviour, impaired social interaction and learning and memory, increased HPA axis activity, peripheral inflammation and microglial activation, and decreased hippocampal neurogenesis in male rodents. Moreover, we found that the combined effect of both stress types resulted in a more severe pathological state defined by increased anxiety- and depressive-like behaviour, impaired social interaction and learning and memory, increased HPA axis activity and central inflammation, and reduced hippocampal neurogenesis and neural plasticity in male rodents. Phenotypes for females were less consistent, irrespective of the type of stress exposure, on account of the limited number of studies using females. This review highlights that the type of stress may indeed matter and will help animal researchers to more appropriately choose a stress/depression model that fits their research purposes.     

The effects of ginger supplementation on markers of inflammatory and oxidative stress: A systematic review and meta‐analysis of clinical trials

The present systematic review and meta‐analysis was conducted to investigate the effects of ginger supplementation on markers of inflammatory and oxidative stress. PubMed, Embase, Scopus, and Web of Science were systematically searched to identify relevant clinical trials evaluating the effects of ginger on serum CRP (C‐reactive protein), TNF‐α (tumor necrosis factor‐alpha), IL‐6 (interleukin‐6), PGE2 (prostaglandin E2), TAC (total antioxidant capacity), and MDA (malondialdehyde) from inception up to September 2019. Mean difference and 95% confidence intervals were pooled using a random‐effects model. Potential publication bias was assessed using visual inspection of funnel plot and Egger's weighted regression tests. After excluding irrelevant records, 20 full‐text articles that included 25 separate studies were included to the meta‐analysis. Pooled results of this study indicated a statistically significant effect of ginger on serum CRP, TNF‐α, IL‐6, TAC, and MDA levels following ginger supplementation in compared to the controls. Also, the effects of ginger on serum PGE2 was marginally significant. Moreover, the high heterogeneity was disappeared in subgroup analysis performed by age, duration, dosage, and quality. This current analysis indicates that ginger supplementation has a significant effects on serum inflammatory and oxidative stress markers.     

Coenzyme Q10 supplementation improves acute outcomes of stroke in rats pretreated with atorvastatin

Objectives: Coenzyme Q10 (CoQ10, ubiquinone) stands among the safest supplements in the elderly to protect against cardiovascular disorders. Noteworthy, CoQ10 deficiency is common in many surviving stroke patients as they are mostly prescribed statins for the secondary prevention of stroke incidence lifelong. Accordingly, the current study aims to experimentally examine whether CoQ10 supplementation in animals receiving atorvastatin may affect acute stroke-induced injury.

Methods: Adult rats underwent transient middle cerebral artery occlusion after atorvastatin pretreatment (5 or 10 mg/ kg/day; po; 30 days) with or without CoQ10 (200 mg/kg/day). After 24 hours ischemic/reperfusion injury, animals were subjected to functional assessments followed by cerebral molecular and histological to detect inflammation, apoptosis and oxidative stress.

Results: Animals dosed with 10 mg/kg presented the worst neurological function and brain damage in the acute phase of stroke injury. CoQ10 supplementation efficiently improved functional deficit and cerebral infarction in all stroke animals, particularly those exhibiting statin toxicity. Such benefits were associated with remarkable anti-inflammatory and anti-apoptotic effects, based on the analyzed tumor necrosis factor-α, interleukin-6, Bax/Bcl2 and cleaved caspase 3/9 immunoblots. Importantly, our fluoro-jade staining data indicated CoQ10 may revert the stroke-induced neurodegeneration. No parallel alteration was detected in stroke-induced oxidative stress as determined by malondialdehyde and 8-oxo-2′-deoxyguanosine levels.

Discussion: These data suggest that all stroke animals may benefit from CoQ10 administration through modulating inflammatory and degenerative pathways. This study provides empirical evidence for potential advantages of CoQ10 supplementation in atorvastatin-receiving patients which may not shadow its antioxidant properties.     

益心舒胶囊治疗病毒性心肌炎气阴两虚证的抗氧化、抗炎作用观察

目的:探讨益心舒胶囊治疗病毒性心肌炎(VMC)气阴两虚证的临床疗效及抗氧化、抗炎的作用。方法:将132例亚急性期VMC患者,采用随机按数字表法分为对照组和观察组各66例。两组均注射用磷酸肌酸钠,1 g/次,1次/d,静脉滴注,连续治疗14 d;辅酶Q10胶囊,1粒/次,3次/d,饭后服用;盐酸曲美他嗪片,1片/次,3次/d,三餐时服用;重症患者,给予地塞米松磷酸钠注射液,10～20 mg/次,1次/d,静脉滴注,连续治疗14 d。对照组口服稳心颗粒,每次1袋,3次/d。观察组口服益心舒胶囊,3粒/次,3次/d。两组疗程均连续治疗8周。监测血清肌钙蛋白I(cTnI)和心肌肌酸磷酸激酶(CK-MB),记录治疗后cTnI,CK-MB的复常率;进行治疗前后心电图检查,记录心电图复常率;进行治疗前后气阴两虚证评分;检测治疗前后肌酸磷酸激酶(CPK),羟丁酸脱氢酶(HBDH),乳酸脱氢酶(LDH)和天门冬氨酸氨基转移酶(AST)水平;进行治疗前后超声心动图检查,记录治疗前后左心室射血分数(LVEF),心脏指数(CI)和舒张早期/舒张晚期最大血流速度(E/A);检测治疗前后超氧化物歧化酶(SOD),丙二醛(MDA),谷胱甘肽过氧化物酶(GSH-Px),干扰素-γ(IFN-γ),白细胞介素-10(IL-10),IL-17和IL-35水平。结果:采用秩和检验分析两组临床疗效,观察组优于对照组(Z=2. 151,P0. 05);观察组cTnI,CK-MB和心电图复常率分别为82. 26%(51/62),90. 32%(56/62)和80. 65%(50/62)分别高于对照组的65. 00%(39/60),73. 33%(44/60)和63. 33%(38/60)(P0. 05);观察组患者血清cTnI,CK-MB,CPK,HBDH,LDH和AST水平均低于对照组(P0. 01);观察组患者LVEF,CI和E/A均高于对照组(P0. 01);观察组SOD和GSH-Px水平均高于对照组(P0. 01),MDA水平低于对照组(P0. 01);观察组IL-10和IL-35水平均高于对照组(P0. 01),IFN-γ和IL-17水平均低于对照组(P0. 01)。结论:在西医常规治疗的基础上,加用益心舒胶囊治疗亚急性期VMC气阴两虚证患者,可通过抗炎和抗氧化作用而保护心肌,临床能起到降低心肌酶,促进心电图、心酶等恢复,改善心功能,提高临床治疗的效果。     

蜘蛛香环烯醚萜部位干预CUMS致抑郁小鼠脑组织的1H-NMR代谢组学分析

目的:利用代谢组学技术分析慢性温和不可预知应激(CUMS)抑郁模型小鼠脑组织样本,寻找与抑郁相关的差异代谢物,探讨蜘蛛香环烯醚萜部位(IEFV)可能的抗抑郁作用机制。方法:42只昆明小鼠随机分为6组,包括正常组,模型组,氟西汀组(2.5 mg·kg-1),IEFV低、中、高剂量组(给药剂量分别为5.73,11.47,22.94 mg·kg-1)。采用CUMS对小鼠造模,以IEFV及阳性药(氟西汀)为干预药物,用行为指标和生化指标进行药效学评价。采用核磁共振氢谱(1H-NMR)代谢组学技术分析IEFV对CUMS抑郁模型小鼠脑组织中内源性物质的影响,结合多变量统计分析方法来确认差异代谢物,并对差异代谢物参与的代谢通路进行富集。结果:造模后,小鼠的不动时间大幅度提高、蔗糖偏好率明显下降,兴奋性神经递质5-羟色胺和去甲肾上腺素显著下降,表明造模成功。给予IEFV和氟西汀后,小鼠不动时间、蔗糖偏好率和兴奋性神经递质向正常水平回调,提示给药后抑郁状态得到了一定程度的缓解。脑组织中内源性代谢物主成分分析(PCA)结果显示,模型组可与正常组明显分开,同时IEFV低、中、高剂量组和氟西汀组均显示有偏离模型组向正常组靠拢的趋势,与行为学结果一致。模型组与正常组进行正交偏最小二乘法-判别分析(OPLS-DA)得到了16个变化显著的差异代谢物,包括12个水溶性差异代谢物和4个脂溶性差异代谢物。通过MetPA数据库分析得到7条潜在靶标代谢通路,包括三羧酸循环(TCA),牛磺酸和亚牛磺酸的代谢,丙氨酸、天冬氨酸和谷氨酸代谢等。IEFV高剂量组可显著回调11种差异代谢物。结论:IEFV可能主要通过影响能量代谢,氨基酸代谢和神经递质水平发挥抗抑郁作用,可为IEFV抗抑郁作用机制的深入研究提供参考依据。     

四君子汤合四磨汤加减治疗出口梗阻型便秘吻合器经肛门直肠切除术后的临床疗效

目的:观察四君子汤合四磨汤加减治疗出口梗阻型便秘(OOC)吻合器经肛门直肠切除术后(STARR)的临床疗效。方法:124例患者随机按数字表法分为对照组和观察组各62例。对照组术后给予芪蓉润肠口服液,20 mL/次/,3次/d;观察组术后给予四君子汤合四磨汤加减内服,1剂/d。两组疗程均连续治疗4周,并进行8周随访。分别于手术前、治疗后2周,4周、随访8周进行便秘主要症状评分和Longo ODS评分;于手术前和治疗后4周,进行超氧化物歧化酶(SOD),丙二醛(MDA)和便秘患者生存质量自评量表(PAC-QOL)评价,并进行肛门直肠测压,记录肛管静息压(ARP),肛管最大收缩压(MSP),直肠排便压力(RSP),初始感觉阈值(FSV),排便感觉阈值(CRS)和最大耐受容量(MTV)等指标;随访记录并发症发生率、复发率和排便正常率;术后4周进行满意度评价和安全性评价。结果:治疗后4周,观察组患者临床疗效优于对照组(Z=2.096,P0.05);治疗后2周,4周和随访8周,观察组便秘主要症状积分和Longo ODS评分均低于对照组(P0.01);观察组患者ARP,FSV,FSV,CRS均低于对照组(P0.01),MSP和RSP均高于对照组(P0.01);观察组并发症发生率、复发率分别为20.97%(13/62)和4.84%(3/62),分别低于对照组的39.71%(24/62)和16.13%(10/62)(P0.05);观察组排便正常率为91.94%(57/62),高于对照组的80.65%(50/62),组间差异无统计学意义;观察组PAC-QOL总分和各因子评分均低于对照组(P0.01);观察组SOD水平高于对照组,MDA水平低于对照组(P0.01);未发现干预中药相关不良反应。结论:四君子汤合四磨汤加减用于出口梗阻型便秘STARR术后患者,可进一步减轻便秘症状和病情程度,提高生活质量,降低术后并发症发生率和复发率,并可改善肛门直肠动力学指标和氧化应激指标,提高临床疗效。     

Combined administration of lauric acid and glucose improved cancer‐derived cardiac atrophy in a mouse cachexia model

Cancer‐derived myocardial damage is an important cause of death in cancer patients. However, the development of dietary interventions for treating such damage has not been advanced. Here, we investigated the effect of dietary intervention with lauric acid (LAA) and glucose, which was effective against skeletal muscle sarcopenia in a mouse cachexia model, on myocardial damage. Treatment of H9c2 rat cardiomyoblasts with lauric acid promoted mitochondrial respiration and increased ATP production by Seahorse flux analysis, but did not increase oxidative stress. Glycolysis was also promoted by LAA. In contrast, mitochondrial respiration and ATP production were suppressed, and oxidative stress was increased in an in vitro cachexia model in which cardiomyoblasts were treated with mouse cachexia ascites. Ascites‐treated H9c2 cells with concurrent treatment with LAA and high glucose showed that mitochondrial respiration and glycolysis were promoted more than that of the control, and ATP was restored to the level of the control. Oxidative stress was also reduced by the combined treatment. In the mouse cachexia model, myocardiac atrophy and decreased levels of a marker of muscle maturity, SDS‐soluble MYL1, were observed. When LAA in CE‐2 diet was orally administered alone, no significant rescue was observed in the cancer‐derived myocardial disorder. In contrast, combined oral administration of LAA and glucose recovered myocardial atrophy and MYL1 to levels observed in the control without increase in the cancer weight. Therefore, it is suggested that dietary intervention using a combination of LAA and glucose for cancer cachexia might improve cancer‐derived myocardial damage.