橙皮苷对慢性应激抑郁模型大鼠行为学及HPA轴的影响

目的:观察橙皮苷对慢性应激抑郁模型大鼠行为学及下丘脑-垂体-肾上腺(HPA)轴的影响.方法:采用慢性轻度不可预见性应激(CUMS)制备大鼠抑郁模型,60只雄性SD大鼠随机分为正常组、模型组、橙皮苷(40,80,160 mg· kg-1)组及阳性药氟西汀(10mg.kg-1)组.连续灌胃给药3周,糖水偏爱实验和强迫游泳实验测定动物行为学,检测血清皮质酮(CORT)、肾上腺指数、下丘脑促肾上腺皮质激素释放激素(CRF) mRNA以及下丘脑室旁核糖皮质激素受体(GR)蛋白,探讨橙皮苷的抗抑郁作用及机制.结果:与模型组相比,橙皮苷(40,80,160 mg·kg-1)治疗组大鼠的糖水消耗量均明显增加、强迫游泳不动时间有不同程度的减少.同时,橙皮苷能逆转CUMS大鼠过高的血清CORT水平和肾上腺指数,并能抑制CUMS大鼠下丘脑CRF mRNA表达、上调室旁核GR蛋白表达.结论:橙皮苷能有效改善CUMS大鼠行为学,表现出抗抑郁作用,其机制可能与调节HPA轴的功能有关.     

CUMS所致大鼠抑郁行为的性别差异与HPA轴功能及BDNF表达相关性研究

目的探讨慢性轻度不可预见性刺激(CUMS)所致大鼠抑郁行为性别差异与下丘脑-垂体-肾上腺皮质轴(HPA)及脑源性神经营养因子(BDNF)表达的相关性。方法选择雌雄各半的远交群SD大鼠64只,以随机数字表格法为分配依据分雌性对照组、雄性对照组、雌性模型组以及雄性模型组,每组16只。应用CUMS以及孤养模式来建立大鼠抑郁模型。应用糖水消耗及高架迷宫法评估大鼠抑郁行为程度,应用Western-blot法检测下丘脑促肾上腺皮质激素释放因子(CRF)mRNA蛋白表达及转录水平,应用荧光定量PCR法检测大鼠海马BDNF mRNA蛋白表达及转录水平,应用放射免疫法检测大鼠血清皮质酮(CORT)含量。结果雌性模型组与雄性模型组高架迷宫开放臂次数、开放臂停留时间、糖水偏爱率、向下探究次数均显著少于雌性对照组与雄性对照组(P均<0.05),血清CORT含量、下丘脑CRF mRNA蛋白表达及转录水平均明显高于雌性对照组与雄性对照组(P均<0.05),而大鼠海马BDNF mRNA蛋白表达及转录水平则明显低于雌性对照组与雄性对照组(P均<0.05)。雄性模型组大鼠进入高架迷宫开放臂与关闭臂次数、中央停留时间、糖水偏爱率、向下探究次数、血清CORT含量、下丘脑CRF mRNA蛋白表达及转录水平明显低于雌性模型组(P均<0.05),但关闭臂停留时间显著长于雌性模型组(P<0.05)。结论 CUMS所致大鼠抑郁行为的性别差异与HPA轴功能及BDNF表达有密切关系,可为抑郁症的防治及机制研究提供有力实验依据。     

当归补血汤对慢性轻度不可预见性刺激抑郁模型大鼠行为学及HPA轴的影响

目的:观察当归补血汤对慢性轻度不可预见性刺激郁模型大鼠行为学和下丘脑-垂体-肾上腺皮质轴(HPA轴)的影响。方法:将120只SD雄性大鼠随机分为正常组、模型组、当归补血汤高、中、低剂量组(8,4,2 g·kg-1)和阳性药组(盐酸氟西汀,3.33 mg·kg-1)。除正常组外,其余各组采用慢性轻度不可预见性刺激法(CUMS)制备抑郁大鼠模型。各给药组动物灌胃给相应药物,正常组和模型组大鼠灌胃给予等体积生理盐水;每日1次,连续21 d。分别于第0,7,14,21天采用强迫游泳实验、悬尾实验和旷场实验等方法对抑郁模型大鼠的行为学改变进行检测,并于21 d采用酶联免疫吸附测定法(ELISA)检测大鼠血清促肾上腺皮质激素(ACTH)和皮质酮(CORT)水平,采用实时荧光定量聚合酶链式反应法(Real-time PCR)检测大鼠下丘脑促肾上腺皮质激素释放激素(CRH),下丘脑、垂体和海马糖皮质激素受体(GR)mRNA表达水平。结果:当归补血汤高、中剂量组可显著减少抑郁模型大鼠强迫游泳实验和悬尾实验的不动时间(P0.05);显著增多旷场实验穿格数次数(P0.05);显著降低血清CORT和ACTH水平(P0.05);当归补血汤高剂量组可下调CRH mRNA表达水平;上调下丘脑、垂体和海马的GR mRNA的表达水平(P0.05)。结论:当归补血汤具有改善CUMS大鼠抑郁行为的作用,表现出抗抑郁作用,其调节HPA轴功能是抗抑郁作用的重要机制之一。     

舒郁散对慢性应激抑郁大鼠行为及海马BDNF表达的影响

目的观察中药舒郁散对慢性应激抑郁大鼠的行为学变化和海马脑源性神经营养因子(BDNF)蛋白表达的影响。方法 50只SD大鼠随机分为正常对照组、模型组、百忧解组、舒郁散小剂量组、舒郁散大剂量组;对大鼠进行21 d的应激刺激建立慢性应激抑郁大鼠模型,观察各组糖水摄入量及强迫游泳测试等行为学指标变化,用免疫组化方法检测大鼠BDNF蛋白表达。结果造模后,模型组大鼠糖水消耗明显下降;大剂量舒郁散能明显增加慢性应激抑郁大鼠的糖水消耗量,能明显缩短抑郁大鼠游泳不动时间,与模型组比较有显著差异;模型组大鼠海马BDNF蛋白表达减少,大剂量舒郁散给药后海马BDNF蛋白表达阳性细胞明显增加,且较模型组明显。结论舒郁散可改善慢性应激抑郁大鼠行为、具有抗抑郁的作用,其抗抑郁作用可能与增加海马BDNF蛋白表达有关。     

舒郁宁心方对慢性应激抑郁模型大鼠行为学及海马BDNF、TrkB表达的影响

目的 观察舒郁宁心方对慢性应激抑郁模型大鼠行为学以及海马脑源性神经营养因子（brain derived neurotrophic factor,BDNF） 及其主要受体酪氨酸激酶B（tyrosine kinase B,TrkB）表达的影响,探讨其抗抑郁机制。方法 将60只成年SD大鼠随机分为正常对照组、模型组、西药组及中药大、中、小剂量组,每组10只。对大鼠进行21天的应激刺激建立慢性应激抑郁模型。除正常对照组外,其他5组大鼠在造模第22天开始灌胃,模型组灌胃生理盐水,中药大、中、小剂量组分别给予25.0、7.5、2.5 g/kg舒郁宁心方灌胃;西药组给予盐酸氟西汀混悬液（12 mg/kg）灌胃;均连续给药3周。分别于0（造模前）、3周（造模成功后）、6周（给药结束后）测定每只大鼠体重;敞箱实验检测大鼠行为学;强迫游泳实验记录大鼠5 min内不动时间。实验结束后脑区取材,测定大鼠脑组织中BDNF及TrkB表达水平。结果 与正常对照组比较,模型组大鼠体重增长缓慢,行为学指标下降,强迫游泳不动时间延长,海马BDNF及TrkB表达减弱,差异均有统计学意义（P<0.05,P<0.01）。给药结束后,中药大剂量组和西药组大鼠体重增加,大鼠行为学改善,强迫游泳不动时间缩短,海马BDNF、TrkB表达增强,与模型组比较,差异均有统计学意义（P<0.05,P<0.01）。结论 舒郁宁心方可能通过改善脑组织BDNF和TrkB的表达水平发挥抗抑郁作用。     

针刺对慢性应激抑郁模型大鼠HPA轴的影响

目的探讨抑郁症的神经生物学发病机制,揭示针刺治疗抑郁症的机理。方法以Wistar大鼠为受试对象,采用给予孤养大鼠以长期不可预见的中等强度刺激的方法建立抑郁大鼠模型,检测应激后造成的抑郁模型大鼠行为学改变、下丘脑-垂体-肾上腺皮质轴(hypothalamus-pituitary-adrenocorticalaxis HPA)的变化,同时观察针刺干预效应及不同针法的疗效比较。结果模型组、生理盐水组血清CORT和ACTH含量明显高于正常对照组(P<0.05);手针治疗组、电针治疗组血清CORT和ACTH含量明显低于模型组(P<0.05);药物组血清CORT和ACTH含量明显低于生理盐水组(P<0.05);手针治疗组、电针治疗组、药物组比较差别无统计学意义。结论针刺百会、太冲具有较明显的抗抑郁效应,其机制可能与针刺对HPA轴的调整有关。     

四逆散对抑郁模型大鼠HPA轴、海马BDNF及其受体TrKB的影响

目的：探讨四逆散的高、低剂量组对抑郁模型大鼠下丘脑-垂体-肾上腺轴（HPA轴）、海马脑源性神经营养因子（BDNF）及其受体型酪氨酸激酶B（TrKB）表达的影响。方法：SD雄性大鼠50只,随机分为正常对照组、模型组、盐酸文拉法辛组（12.5 mg·kg^-1）、四逆散高、低剂量组（10,5 g·kg^-1）。采用慢性轻度不可预见性刺激造模,同时ig给药21 d后分别取血、下丘脑和海马。采用放射免疫分析法检测大鼠血浆皮质醇（CORT）、促肾上腺皮质激素（ACTH）及下丘脑中促肾上腺皮质激素释放激素（CRH）的含量变化,采用免疫组化分析法检测海马BDNF及其TrKB阳性神经元面密度值的变化。结果：与正常组相比,模型组大鼠血浆中CORT,ACTH及下丘脑CRH的含量明显升高,海马中BDNF和TrKB的神经面密度值明显降低。与模型组相比,四逆散高、低剂量组可以显著降低抑郁症模型大鼠血浆CORT,ACTH、下丘脑CRH的含量;增加大鼠海马BDNF及其TrKB阳性神经元面密度值。结论：四逆散可明显改善抑郁模型大鼠的抑郁状态,其机制可能是通过HPA轴增加海马BDNF,TrKB的表达。     

舒郁宁心方对慢性应激抑郁模型大鼠行为学及海马BDNF,TrkB表达的影响

目的:分析中药舒郁宁心方对慢性应激抑郁模型大鼠行为学及海马脑源性神经营养因子(brain-derived neurotrophic factor,BDNF),酪氨酸激酶B(tyrosine kinase B,TrkB)表达的影响。方法:选取60只雄性SD大鼠,随机分为正常组、模型组、西药组(氟西汀)、舒郁宁心方低、中、高剂量组,每组各10只,除正常组外,均建立为期21 d的慢性应激抑郁模型。建模2周后起,进行为期21 d的给药。其中正常组不给药,模型组ig生理盐水,西药组ig氟西汀药液12 mg·kg^-1,中药低、中、高剂量组分别ig舒郁宁心方药液2.5,7.5, 25.0 g·kg^-1。对比各组大鼠在第1天(造模前)和第56天(给药结束后)的体重、糖水摄入量、水平运动格数、垂直运动次数。对比实验结束后各组大鼠海马组织中BDNF和TrkB的表达水平。结果:第56天与正常组比较,模型组的体重、糖水摄入量、水平运动格数、垂直运动次数及CA1区和CA3区的BDNF和TrkB阳性表达的积分吸光度(IA)显著降低(P<0.05);与模型组比较,氟西汀组和舒郁宁心方各剂量组上述指标显著升高(P<0.05)。结论:舒郁宁心方可以改变海马组织中的BDNF和TrkB表达水平,进而起到一定的抗抑郁疗效。     

佛手挥发油的抗抑郁作用机制探讨

目的:在探讨佛手挥发油对慢性应激所致大鼠抑郁模型(CUMS)的干预作用.方法:90只Wistar大鼠随机分为6组,每组15只,分别为空白对照组、模型组、阳性药组(10 mg? kg -1氟西汀ig 21 d)、佛手挥发油低、中、高剂量(150,300,600mg?kg-1佛手挥发油ig21 d).除空白对照组外,其余5组大鼠经历21 d慢性应激造成抑郁模型,各组大鼠造模同时给予相应药物.21 d慢性应激后以糖水偏爱和旷场测试测定动物的行为变化,放免法测定大鼠血清中皮质酮(CORT)水平,蛋白免疫印迹法测定脑组织神经营养因子(BDNF)的蛋白表达水平.结果:与正常组大鼠比较,模型组经过慢性应激3周后大鼠糖水偏好由(88.1±13.3)％降至(60.5±9.8)％旷场水平评分及垂直评分分别由(123.5±21.3)和(38.2±5.9)降为(72.5±12.7)和(17.1±5.1),表明慢性应激导致大鼠产生抑郁样行为;同时,抑郁大鼠的血清CORT水平由(42.1±7.7) μg?L-1增加为(117.6±19.3) μg?L-1,海马BDNF表达水平由(0.22±0.04)降为(0.07±0.02).佛手挥发油干预治疗后能呈剂量依赖地改善由慢性应激所致的大鼠抑郁行为及生化指标改变.其中300,600 mg?kg-1佛手挥发油组糖水偏好分别为(70.7±10.2)％和(77.1±11.9)％,与抑郁组比较有显著的统计学差异(分别为P＜0.05和P＜0.01);150,300,600 mg?kg-1佛手挥发油组旷场水平评分分别为(87.7±15.4),(98.3±19.7),(110.3±28.9),与抑郁组比较有显著差异(P ＜0.05,P＜0.01);300,600 mg?kg -1佛手挥发油组旷场垂直评分分别为(24.5±6.3),(29.2±7.2),与抑郁组比较有显著差异(P＜0.05,P＜0.01);皮质酮浓度分别为(90.1±13.5),(77.5±10.7) μg?L-1,与抑郁组比较有显著差异(P ＜0.05,P＜0.01);300,600 mg?kg-1佛手挥发油组海马BDNF相对含量为(0.15±0.03)和(0.18±0.03),与抑郁组比较有显著的统计学差异(分别为P＜0.05和P＜0.01).结论:佛手挥发油的抗抑郁作用机制可能与调节血清CORT水平和海马组织BDNF表达水平有关.     

电针对慢性应激抑郁模型大鼠糖皮质激素及其受体基因表达的影响

目的:观察电针对慢性应激模型大鼠糖皮质激素及其受体的影响,进而探讨电针抗抑郁的作用机制。方法:SD大鼠随机分为空白组、模型组、百优解组、束缚组、电针组、糖皮质激素拮抗剂组、电针加糖皮质激素拮抗剂组,每组10只。采用慢性应激结合孤养21d造模。选取"百会"透"印堂"穴电针治疗慢性应激模型大鼠,用糖皮质激素受体拮抗剂RU486阻断下丘脑-垂体-肾上腺(HPA)轴的负反馈通路。放射免疫法检测肾上腺皮质酮含量,实时荧光定量逆转录-聚合酶链式反应法检测海马、下丘脑、垂体糖皮质激素受体(GR)mRNA的表达。结果:与空白组比较,束缚组大鼠肾上腺皮质酮的分泌明显增多(P0.05),而电针组与束缚组比较皮质酮的过度分泌明显降低(P0.05)。束缚组大鼠GRmRNA在海马、下丘脑及垂体的表达显著下降(P0.05),电针组与束缚组比较海马、下丘脑、垂体GR的生成增多(P0.05)。以上两指标,模型组和糖皮质激素拮抗剂组的变化与束缚组一致;与模型组比较,百优解组仅可明显升高海马GRmRNA的表达(P0.05);与糖皮质激素拮抗剂组比较,电针加糖皮质激素拮抗剂组可降低肾上腺皮质酮的含量(P0.05),升高海马GRmRNA的表达(P0.05),但其降低肾上腺皮质酮含量和升高下丘脑、垂体GRmRNA表达的作用均不及电针组(P0.05)。结论:电针对糖皮质激素的过度分泌有直接的调控作用,并可通过增强GRmRNA的表达,改善HPA轴负反馈中枢的功能障碍。当HPA轴负反馈通路被阻断后,电针的作用减弱。     

基于代谢通路调控的沙棘籽油抗抑郁作用机制研究

目的采用1H-NMR代谢组学技术结合KEGG数据库,分析沙棘籽油干预慢性温和不可预知应激(CUMS)抑郁大鼠血清和尿液中代谢物及其代谢通路的变化,探讨沙棘籽油抗抑郁的作用机制。方法复制CUMS模型,同步给予沙棘籽油干预,连续4周。采集大鼠血清和尿液进行1H-NMR检测,利用代谢组学技术分析血清和尿液中代谢物的变化,搜索KEGG数据库分析代谢通路。结果在血清和尿液中共寻找出17个与抑郁症相关的潜在生物标志物,其中血清中有9个,包括与对照组比较升高的脂质、β-羟基丁酸、乳酸、N-乙酰糖蛋白和降低的丙氨酸、甜菜碱、氧化三甲胺、α-葡萄糖、β-葡萄糖;尿液中有8个,包括与对照组比较升高的琥珀酸酯、天冬氨酸盐和降低的醋酸、2-酮戊二酸、柠檬酸、三甲胺、甜菜碱、苯丙氨酸。沙棘籽油干预后上述差异代谢物均出现了不同程度的回调,接近对照组水平。结论沙棘籽油主要是通过调节体内的能量代谢、脂质代谢、氨基酸代谢、甲胺代谢和神经递质的合成等代谢通路发挥抗抑郁作用。     

Antidepressant-like effect of magnolol on BDNF up-regulation and serotonergic system activity in unpredictable chronic mild stress treated rats

Magnolol is the main constituent identified in the barks of Magnolia officinalis, which has been used for the treatment of mental disorders including depression in China. In this study, we investigated the antidepressant‐like effect of magnolol, and its possible mechanisms in rats subjected to unpredictable chronic mild stress (UCMS). High performance liquid chromatography with electrochemical detection (HPLC‐ECD) and immunohistochemical staining analysis were applied to explore the mechanisms underlying the antidepressant‐like effect of magnolol. Magnolol (20, 40 mg/kg) significantly reversed UCMS‐induced reduction in sucrose consumption and deficiency in locomotor activity. In addition, it was observed that administration of magnolol (20, 40 mg/kg) restored brain‐derived neurotrophic factor (BDNF) expression, and normalized the serotonergic system changes in the UCMS‐treated rats. These results confirmed the antidepressant‐like effect of magnolol, which might be based primarily on its ability to increase the BDNF expression and enhance the activity of the serotonergic system in rat brains. Copyright © 2012 John Wiley & Sons, Ltd.     

Essential oil of Perilla frutescens-induced change in hippocampal expression of brain-derived neurotrophic factor in chronic unpredictable mild stress in mice

Ethnopharmacological relevance

Perilla frutescens (Perilla leaf), a traditional Chinese medicinal herb, has been used for centuries to treat various conditions including depression. A previous study of the authors demonstrated that essential oil of Perilla frutescens (EOPF) attenuated the depressive-like behavior in mice.

Aim of the study

This study was undertaken to explore the dynamic change of behaviors and brain-derived neurotrophic factor (BDNF) expression induced by chronic unpredictable mild stress (CUMS), and improved by EOPF.

Materials and methods

Four separate CUMS experimental groups (1-week, 2-week, 3-week and 4-week treatment) were treated with EOPF (3 mg/kg and 6 mg/kg, p.o.) or fluoxetine (20 mg/kg, p.o.), followed by sucrose preference, locomotor activity, immobility and hippocampal BDNF measurement.

Results

EOPF, as well as fluoxetine, restored the CUMS-induced decreased sucrose preference and increased immobility time, without affecting body weight gain and locomotor activity. Furthermore, CUMS (3 or 4-week) produced a reduction in both BDNF mRNA and protein expression in the hippocampus, which were ameliorated by EOPF (4-week) and fluoxetine (3 or 4-week) treatment.

Conclusion

These results presented here show that BDNF is expressed depending on length of CUMS procedure and EOPF administration. And this study might contribute to the underlying reason for the slow onset of antidepressant activity in clinic.     

交泰丸对慢性温和不可预知性应激抑郁模型大鼠炎性细胞因子的影响

目的探讨交泰丸对慢性温和不可预知性应激(CUMS)抑郁模型大鼠致炎、抗炎细胞因子的影响。方法大鼠采用CUMS方法制备抑郁模型,比较体质量变化,进行糖水消耗实验和开场实验;并采用酶联免疫吸附测定法(ELISA)测定大鼠血清及海马组织中炎性细胞因子白细胞介素(IL)-1β、IL-6、肿瘤坏死因子(TNF)-α、IL-4、IL-10的水平,尼氏染色法观察大鼠海马神经元形态。结果与对照组比较,模型组大鼠糖水消耗量、穿越横格数和直立次数均明显减少;血清及海马内IL-1β、IL-6、TNF-α、IL-4明显升高,IL-10明显降低;海马神经元分层不清,排列紊乱,尼氏体浅染或消失。与模型组比较,交泰丸给药组大鼠糖水消耗量、穿越横格数和直立次数均明显增加;血清及海马内IL-1β、IL-6、TNF-α明显降低,IL-4、IL-10明显升高;海马神经元分层较明显,尼氏体浅染。结论交泰丸可明显改善大鼠抑郁样行为及海马神经元损伤,其机制可能与下调血清及海马致炎细胞因子IL-1β、IL-6、TNF-α和上调抗炎细胞因子IL-4、IL-10表达有关。     

Antidepressant effect of Shudihuang on mice exposed to unpredictable chronic mild stress

Aim of the study

Depression is a severe mood disorder. It was treated with Shudihuang, the steamed roots of Rehmannia glutinota Libosch. (SRG), in traditional Chinese medicine. The present paper was designed to verify its antidepressant effect.

Materials and methods

A mouse model of depression was established though unpredictable chronic mild stress (UCMS). Low and high doses of SRG were administered orally. Fur state, body and organ weight, and gastric ulcers were examined. Locomotion was assayed in open field test. Liver antioxidant indexes were measured spectrophotometrically.

Results

Fur state, body and organ weight were found to be insensitive to UCMS. The locomotion reduced by UCMS was restored by low dose of SRG (2.5 g/kg BW) but not by high dose (5 g/kg BW). UCMS resulted in aggravated gastric ulceration, elevated liver malondialdehyde, together with reduced total antioxidant capability, glutathione content, and superoxide dismutase and catalase activities. The alterations were improved by SRG in a dose-dependent manner. The differences in the activity of glutathione peroxidase were statistically nonsignificant among groups. Clomipramine the positive drug was similar to SRG especially in antioxidation.

Conclusion

SRG is of therapeutic value for depression-like disorders, and antioxidation may be one of the mechanisms underlying its antidepressant action.     

表没食子儿茶素没食子酸酯对慢性温和不可预知应激抑郁小鼠的保护作用

目的研究表没食子儿茶素没食子酸酯(EGCG)的抗抑郁作用。方法制备慢性温和不可预知应激(CUMS)刺激小鼠抑郁模型;通过旷场实验、体质量、糖水偏爱率、强迫游泳实验和悬尾实验静止时间等指标考察EGCG的抗抑郁作用;检测血清皮质酮(CORT)、促肾上腺皮质激素(ACTH)水平;检测海马组织丙二醛(MDA)水平及超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)活性;实时定量PCR(RT-PCR)检测海马组织中吲哚胺2,3-双加氧酶(IDO)、白细胞介素-1β(IL-1β)、IL-6 m RNA表达。结果 EGCG改善小鼠抑郁状态行为活动;降低血清CORT、ACTH水平;减少海马中MDA的量,提高SOD、GSH-Px活性,下调IDO、IL-6及IL-1βm RNA表达。结论 EGCG可改善小鼠抑郁症状,其机制可能与降低血清中CORT、ACTH水平,抑制海马中MDA的生成,促进SOD、GSH-Px分泌,以及下调IDO、IL-6、IL-1β基因表达有关。     

Herbal formula SYJN increases neurotrophin-3 and nerve growth factor expression in brain regions of rats exposed to chronic unpredictable stress

Aim of the study

SYJN is a Chinese herbal formula that contains four herbs: Bupleurum chinense DC., Curcuma aromatica Salisb., Perilla frutescens (L.) Britt., and Acorus tatarinowii Schott. Previous studies conducted in our laboratory have revealed an antidepressant-like effect of the formula in chronic unpredictable stress (CUS)-induced depression model in rats. The present study aimed to investigate whether neurotrophin-3 (NT-3) and nerve growth factor (NGF) are involved in the antidepressant-like action of SYJN by using the same depressive model in rats.

Materials and methods

Rats were subjected to an experimental setting of CUS. The mechanism underlying the antidepressant-like action of SYJN was examined by measuring protein and mRNA expression of NT-3 and NGF in brain tissues of CUS-exposed rats.

Results

The results showed that NT-3 protein and mRNA expression in the hippocampus and frontal cortex were significantly decreased in CUS-treated rats. CUS treatment also significantly decreased NGF protein and mRNA expression in the frontal cortex of the animals. Daily intragastric administration of SYJN (1300 or 2600 mg/kg/day) during the 4 weeks of CUS significantly suppressed these changes induced by CUS.

Conclusion

The results suggest that the antidepressant-like activity of SYJN is likely mediated by the increases in NT-3 and NGF expression in brain tissues.     

L‐theanine ameliorate depressive‐like behavior in a chronic unpredictable mild stress rat model via modulating the monoamine levels in limbic–cortical–striatal–pallidal–thalamic‐circuit related brain regions

L‐theanine, originally found in green tea, elicits various physiological effects, such as promoting relaxation, improving concentration and learning ability, and providing antianxiety‐like and antidepressant‐like properties. This study aims to investigate the effects of L‐theanine (2 mg/kg) on monoamine levels in an animal model of depression. The effect of l ‐theanine on the symptoms of depression was examined through the open‐field test, sucrose preference test, and forced swim test. The monoamine neurotransmitters that involve serotonin (5‐HT), norepinephrine (NE), and dopamine (DA) were measured in the limbic–cortical–striatal–pallidal–thalamic (LCSPT)‐circuit related brain regions, including the prefrontal cortex (PFC), nucleus accumbens (NAC), striatum (ST), amygdala, and hippocampus (HIP). L‐theanine ameliorated the depressive‐like behaviors in the chronic unpredictable mild stress (CUMS) rat model. In the PFC, NAC, and HIP, L‐theanine administration significantly increased the levels of 5‐HT, NE, and DA. In the ST, the levels of 5‐HT and DA were increased after the administration of L‐theanine. However, in the HIP, only the level of DA significantly changed after the treatment of L‐theanine. Taken together, these results indicated that L‐theanine has possibly antidepressant‐like effects in the CUMS rat model, which could be mediated by the monoamine neurotransmitters in the LCSPT‐circuit related brain regions.     

解郁丸对慢性应激大鼠HPA轴和免疫系统的影响

目的：观察解郁丸对慢性应激抑郁大鼠行为,以及HPA轴和免疫系统的影响,探讨其可能的抗抑郁机制。方法：采用慢性不可预见性应激造成大鼠抑郁模型,大鼠随机分为正常对照组,慢性应激模型组,慢性应激模型+解郁丸(53,106,212 mg·kg^-1低、中、高3个剂量)组,慢性应激模型+丙咪嗪(10 mg·kg^-1)组。运用糖水消耗实验测定动物行为,称量肾上腺和胸腺测定肾上腺指数和胸腺指数,采用ELISA检测血清促肾上腺皮质激素、皮质酮、白介素-1β和肿瘤坏死因子-α的含量。结果：与正常对照组相比,慢性应激大鼠的糖水消耗量下降,肾上腺指数上升,胸腺指数下降,血清促肾上腺皮质激素、皮质酮、白介素-1β和肿瘤坏死因子-α的水平升高,均有显著性差异(P<0.001),提示慢性应激大鼠出现神经-内分泌-免疫功能紊乱。与慢性应激模型组比较,中、高剂量的解郁丸可增加慢性应激大鼠的糖水消耗量(P<0.001),同时降低肾上腺指数(P<0.001),缓解胸腺萎缩(P<0.01),低、中、高剂量的解郁丸可以翻转血清促肾上腺皮质激素、皮质酮、白介素-1β和肿瘤坏死因子-α的水平(P<0.05,P<0.01,P<0.001)。结论：解郁丸的抗抑郁作用可能与逆转慢性应激大鼠HPA轴和免疫功能紊乱有关。