BCEF0083对慢性应激抑郁模型大鼠海马神经元及脑源性神经营养因子mRNA表达的影响研究

目的:研究BCEF0083对慢性应激抑郁模型大鼠海马神经元及脑源性神经营养因子(BDNF)mRNA表达的影响。方法:将大鼠随机分为对照组、模型组、吗氯贝胺20mg/kg组以及BCEF0083100、50、25mg/kg组,用HE染色法观察海马神经元数目的变化,用逆转录-聚合酶链反应法检测海马BDNFmRNA的表达。结果:BCEF0083可增加慢性应激抑郁模型大鼠海马神经元数目及上调BDNFmRNA的表达。结论:BCEF0083的抗抑郁作用可能与增加慢性应激抑郁模型大鼠海马神经元数目及上调BDNFmRNA的表达有关。     

抑郁症：神经元损伤与神经元再生障碍

由于现代社会经济的高速发展与精神需求的显著增强 ,抑郁症发生率逐年提高。在过去 10年中 ,抑郁症已成为世界上最普遍的公共卫生疾病之一 ,并成为“2 1世纪的流行病”。抑郁症发病机制至今不明。经典“单胺假说”认为 ,抑郁症的发生与脑内5 HT和 或NE水平低下有关 ,但不能解释抗抑郁剂为何延迟起效的现实问题。抗抑郁剂效应延迟暗示边缘系统单胺能神经可塑性改变[1,2 ] 。应激事件可以诱发抑郁症已成为不争的事实 ,动物应激模型也被用于模拟抑郁症。与慢性应激状态一样 ,重症抑郁病人海马体积较之正常人显著减小 ,且减小程度与抑郁持续…     

脑源性神经营养因子对大鼠海马神经元GABAA受体效应的影响

目的:观察不同浓度脑源性神经营养因子(BDNF)对大鼠海马神经元γ-氨基丁酸(GABA)A受体效应的影响。方法:原代培养海马神经元,应用BDNF(100、300及1000 ng/L)处理20 min后,施加GABA(终浓度为100μmol/L),5 min后应用流式细胞仪测定细胞内钙离子浓度。采用全细胞膜片钳记录模式,向锥体细胞施加BDNF(100、300及1000 ng/L)2 min,再施加GABA 100μmol/L并持续5 s,记录钳制电位为-60 mV时的GABAA受体电流。将神经元钳制电位从-100 mV至0 mV以10 mV递增,记录BDNF作用下GABAA受体电流的幅度和方向,并绘制电流电压曲线,计算GABAA受体电流的反转电位。结果:BDNF 100 ng/L和300 ng/L对GABA诱发的细胞内钙浓度、GABAA受体电流及反转电位均无影响,但在BDNF 1000 ng/L作用下,GABA诱发的细胞内钙浓度显著增加(P<0.05),GABAA受体电流在钳制电位-60 mV时变为外向电流,并且反转电位由对照的0 mV左移至-93 mV。结论:高浓度BDNF可使GABAA受体电流反转电位左移,导致GABA诱发锥体细胞内钙浓度增高而发挥兴奋效应。     

小补心汤总黄酮的抗抑郁作用及其对慢性应激小鼠神经元再生的影响

目的：小补心汤是由旋复花、代赭石等四味中药组成的传统中药复方，前期研究表明，小补心汤具有抗抑郁作用。本研究小补心汤总黄酮部位(BX-2)的抗抑郁作用及其对慢性应激小鼠神经元再生的影响。方法：(1)采用小鼠强迫游泳、小鼠悬尾、大鼠强迫游泳和5-HTP甩头试验等多个抑郁模型评价BX-2的抗抑郁活     

慢性应激对大鼠海马神经元睫状神经营养因子及其mRNA表达水平的影响

目的　观察慢性应激对大鼠海马神经元CNTF及其mRNA表达水平的变化。方法　采用慢性不可预见性中等强度应激 ,运用旷场实验观察大鼠行为 ;运用免疫组化和原位杂交的方法 ,观察大鼠海马神经元CNTF及其mRNA表达水平的变化。结果　与对照组相比 ,慢性应激组大鼠海马CNTF免疫阳性颗粒数目减少 ,着色浅淡 ;CNTFmRNA杂交阳性信号减少。结论　慢性应激可造成大鼠海马神经元CNTF及其mRNA表达水平降低     

高同型半胱氨酸血症对慢性应激模型大鼠行为学及神经生化的影响

目的研究高同型半胱氨酸血症(Hhcy)对慢性不可预见应激模型大鼠行为学、神经递质及神经营养因子水平的影响。方法以高蛋氨酸饮食喂养大鼠制作Hhcy模型(Hhcy组,12只);另选24只大鼠,均分为普食组和对照组,均给予普通饮食喂养;Hhcy组与普食组给予慢性不可预见性刺激。比较三组的学习记忆能力、海马组织5-羟色胺(5-HT)和5-羟基吲哚乙酸(5-HIAA)含量以及脑脊液中神经营养因子(BDNF)水平。结果水迷宫实验中,Hhcy组目的象限停留时间比普食组短(P<0.05);Hhcy组海马5-HIAA含量和脑脊液中BDNF含量均较普食组低(P<0.05)。结论Hhcy可致慢性应激模型大鼠学习记忆能力的下降,加重神经递质及生长因子水平的异常,可能为抑郁症的危险因素之一。     

黄精总皂苷对慢性应激模型大鼠的行为学以及对海马的BDNF和TrkB表达的影响

目的:通过观察慢性应激对大鼠行为学的变化和海马与大脑皮层脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)及其受体酪氨酸激酶B(tyrosine kinase receptor,TrkB)表达的影响,探讨黄精总皂苷(saponins ofRhizoma Polygonati,SRP)抗抑郁作用及其机制。方法:48只SD大鼠,分为6组:正常组、模型组、氟西汀(fluoxetine,Flu)组(2 mg.kg-1)、SRP低、中、高剂量组(30,60,120 mg.kg-1)。采用不同应激因子交替持续应激21 d复制大鼠慢性应激抑郁模型,观察大鼠行为学指标和实验前后动物学习记忆能力等变化,用免疫组化法测定海马和大脑皮层中BDNF及TrkB的表达。结果:①应激刺激后,行为学指标显示,与正常组相比,模型组大鼠明显处于抑郁状态。②海马、大脑皮层可见到BDNF,TrkB染色阳性细胞,模型组阳性细胞数目及其灰度少于正常组和SRP低、中、高剂量组。结论:SRP能有效地减少慢性应急模型大鼠海马和大脑皮层神经元表达BDNF和TrkB的降低,SRP可能通过减少BDNF和TrkB的降低...     

灯盏花素对大鼠神经元的影响及其与BDNF信号通路的关系

探讨灯盏花素对sD大鼠大脑皮质体外培养神经元生长的影响及其与脑源性神经营养因子（BDNF）信号通路的关系。结果示灯盏花素组在细胞数、胞体面积、突起长度及细胞活力方面均较对照组及正常组升高（P〈0．05）。BDNF及TrkBmRNA的表达在灯盏花素组也较对照组和正常组升高（P〈0．05）。灯盏花素促进sD大鼠脑源性神经元的存活、生长,其机制可能是通过上调BDNF及其受体TrkB的表达。     

17β-雌二醇对卵巢切除小鼠海马内脑源性神经营养因子及神经营养因子 3表达的影响(英文)

目的　为确定雌激素可能具有的神经营养调节作用。方法　采用蛋白质印迹法检测上述指标的变化。结果　与卵巢未切除对照组相比 ,小鼠卵巢切除 10周后海马内脑源性神经营养因子 (BDNF)表达水平明显下降 ,给予 17β 雌二醇 (2 .4或 4 .8μg·d- 1,sc ,连续 12周 )替代具有明显的改善作用 (P <0 .0 1)。但卵巢切除及 17β 雌二醇替代对海马内神经营养因子 3表达水平无明显影响。结论　海马内BDNF表达水平的改变与雌激素缺乏具有密切关系。雌激素对调节海马内BDNF水平具有重要作用。     

乳猪脑提取物和脑活素对培养中胎鼠大脑皮层神经元的影响

从乳猪脑中提取相应的神经营养物质，应用胎鼠大脑皮层细胞培养技术和四唑盐（Ｍ－ＴＴ）微量比色法，观察了乳猪脑提取物和脑活素（Ｃｅｒｅｂｒｏｌｙｓｉｎ）对大脑歧层细胞培养的影响。结果表明，乳猪脑提取物能起明显促进神经元突起生长和支持存活的作用，并存在着剂量作用效应，当提取物剂量为２０ｍｇ／Ｌ时作用效果最佳。脑活素对皮层神经元促突起生长和支持存活的作用不理想。ＭＴＴ微量比色法结果显示，乳猪脑组织提取物能     

Moclobemide up-regulates proliferation of hippocarnpal progenitor cells in chronically stressed mice

AIM: To explore the action mechanism of antidepressants. METHODS: The PC12 cell proliferation was detected by flow cytometry,. The proliferation of hippocampal progenitor cells and level of brain-derived neurotrophic factor (BDNF) were measured by immunohistochemistry. RESULTS: Treatment with N-methylaspartate (NMDA) 600μmol/L for 3 d significantly decreased the percentage of S-phase in PC12 cells, while in the presence of classical antidepressant, moclobemide (MOC) 2 and 10μmol/L, the percentage in S-phase increased. Furthermore, the proliferation of progenitor cells in hippocampal dentate gyrus (subgranular zone), as well as the level of BDNF in hippocampus significantly decreased in chronically stressed mice, while chronic administration with MOC 40 mg/kg (ip) up-regulated the progenitor cell proliferation and BDNF level in the same time course. CONLUSION: Up-regulation of the proliferation of hippocampal progenitor cells is one of the action mechanisms for MOC, which may be closely related to the e     

5-HT7, neurogenesis and antidepressants: a promising therapeutic axis for treating depression

1. There is mounting evidence that a wide range of antidepressants share the common feature of increasing hippocampal neurogenesis. The specificity of this association has suggested that an ability to increase neurogenesis might be a useful paradigm to screen for compounds with antidepressant activity. 2. The hope of developing better antidepressants has stimulated research into the molecular control of neurogenesis and here we summarize some of the recent findings. We also review recent work that highlights 5-HT7 receptor as a promising molecular target in the treatment of depression. 3. In summary, it appears that 5-HT7 antagonism is capable of producing diverse antidepressant-like behavioural effects, alters hippocampal neuronal morphology and synergistically regulates hippocampal neurogenesis.     

Pro‐neurocognitive and anti‐sarcopenic benefits of one‐year metformin therapy in ovariectomized aged mice

Health promotion and healthy nutrition significantly increased life expectancy around the world. Aging is associated with an increase in age‐related diseases. The use of metformin (Met) as an anti‐aging drug has recently been proposed based on its widespread use in clinical practice. Reports have shown that Met acts as an anti‐aging agent. In this study, the effects of long‐term, 1 year, Met administration on aging‐related behaviors and longevity in ovariectomized mice was studied. Met (1 and 10 mg/kg, daily) was administered orally in ovariectomized mice. The anxiety‐like behavior, working memory, and physical strength were measured through elevated plus maze, Y‐maze, vertical grid holding, and the obligatory swimming capacity tests. Brains were harvested to measure brain‐derived neurotrophic factor (BDNF) level. Also, the Kaplan‐Meier survival curves were used to show differences and similarities in survival patterns. Met (10 mg/kg) decreased anxiety‐like behaviors as well as increased muscle strength and working memory in the ovariectomized mice. Moreover, Met increased the physical strength and longevity as well as the level of BDNF in the ovariectomized mice. Our results indicate that Met administration can be an effective strategy for having a healthy aging in the absence of female gonadal hormones and reverses deleterious effects of ovariectomy‐induced aging possibly through BDNF.     

Agmatine increases proliferation of cultured hippocampal progenitor cells and hippocampal neurogenesis in chronically stressed mice

AIM: To explore the mechanism of agmatine's antidepressant action. METHODS: Male mice were subjected to a variety of unpredictable stressors on a daily basis over a 24-d period. The open-field behaviors of the mice were displayed and recorded using a Videomex-V image analytic system automatically. For bromodeoxyuridine (BrdU; thymidine analog as a marker for dividing cells) labeling, the mice were injected with BrdU (100 mg/kg, ip, twice per d for 2 d), and the hippocampal neurogenesis in stressed mice was measured by immunohistochemistry. The proliferation of cultured hippocampal progenitor cells from neonatal rats was determined by colorimetric assay (cell counting kit-8) and 3H-thymidine incorporation assay. RESULTS: After the onset of chronic stress, the locomotor activity of the mice in the open field significantly decreased, while coadministration of agmatine 10 mg/kg (po) blocked it. Furthermore, the number of BrdU-labeled cells in the hippocampal dentate gyrus significantly decreased in chronically stressed mice, which was also blocked by chronic coadministration with agmatine 10 mg/kg (po). Four weeks after the BrdU injection, some of the new born cells matured and became neurons, as determined by double labeling for BrdU and neuron specific enolase (NSE), a marker for mature neurons. In vitro treatment with agmatine 0.1-10 micromol/L for 3 d significantly increased the proliferation of the cultured hippocampal progenitor cells in a dose-dependent manner. CONCLUSION: We have found that agmatine increases proliferation of hippocampal progenitor cells in vitro and the hippocampal neurogenesis in vivo in chronically stressed mice. This may be one of the important mechanisms involved in agmatine's antidepressant action.     

新型磷酸二酯酶4抑制剂氯比普兰改善老年小鼠的认知功能障碍

目的探讨新型磷酸二酯酶4抑制剂氯比普兰(chlorbipram)对老年小鼠学习记忆功能障碍的影响。方法 20月龄和6月龄昆明雄性小鼠,分别随机分为溶剂对照组和氯比普兰给药组(0.5 mg·kg-1),连续给药21 d。旷场实验检测穿越格子数、直立次数和粪便粒数;新物体识别实验(NOR)检测识别指数(RI);水迷宫实验检测逃避潜伏期、穿越平台时间、目标象限停留时间及路程和游泳速度。ELISA法测定海马环磷酸腺苷(c AMP)的含量,Western蛋白印迹法检测磷酸化蛋白激酶A(p-PKA)和磷酸化c AMP反应元件结合蛋白(p-CREB)的水平;逆转录PCR(RT-PCR)检测脑源性神经营养因子(BDNF)mRNA的表达。结果旷场实验结果显示,20月龄正常组小鼠粪便粒数明显多于6月龄正常组小鼠(P<0.05),给予氯比普兰后粪便粒数明显减少。NOR实验结果表明,20月龄正常组小鼠RI明显低于6月龄正常组小鼠(P<0.01),给予氯比普兰后RI明显升高(P<0.05),达到6月龄正常组小鼠水平。水迷宫实验结果显示,与6月龄正常组小鼠相比,20月龄正常组小鼠穿越平台次数明显减少(P<0.01),第一次到达平台时间明显延长(P<0.05),目标象限的探索时间和路程显著性下降(P<0.01);给予氯比普兰明显增加穿越平台次数(P<0.01),缩短第一次到达平台时间(P<0.05),延长在目标象限探索的时间和路程(P<0.01)。ELISA分析结果显示,20月龄正常组小鼠海马c AMP水平明显低于6月龄正常组小鼠(P<0.01),氯比普兰能显著增加海马c AMP含量(P<0.01)。Western蛋白印迹结果显示,20月龄正常组小鼠海马内p-PKA和p-CREB的蛋白表达明显低于6月龄正常组小鼠(P<0.01),氯比普兰能够增强p-PKA和p-CREB表达(P<0.01)。RTPCR结果表明,20月龄正常组小鼠海马内BDNF mRNA水平明显低于6月龄正常组小鼠(P<0.01),给予氯比普兰能显著提高BDNF mRNA水平(P<0.01)。结论氯比普兰可以通过影响c AMP水平,上调p-PKA和p-CREB蛋白表达,促进BDNF的转录,从而改善老年小鼠的认知功能障碍。     

Antidepressant-like effects of ginsenoside Rg1 are due to activation of the BDNF signalling pathway and neurogenesis in the hippocampus

BACKGROUND AND PURPOSE Ginsenoside Rg1 (Rg1) is one of the major bioactive ingredients of Panax ginseng with little toxicity and has been shown to have neuroprotective effects. In this study, we investigated the antidepressant-like effect of Rg1 in models of depression in mice. EXPERIMENTAL APPROACH The effects of Rg1 were assessed in the forced swimming test (FST) and tail suspension test (TST) in mice. Rg1 was also investigated in the chronic mild stress (CMS) mouse model of depression with imipramine as the positive control. Changes in hippocampal neurogenesis and spine density, the brain-derived neurotrophic factor (BDNF) signalling pathway, and serum corticosterone level after chronic stress and Rg1 treatment were then investigated. The tryptophan hydroxylase inhibitor and the tyrosine kinase B inhibitor were also used to explore the antidepressive mechanisms of Rg1. KEY RESULTS Ginsenoside Rg1 exhibited antidepressant-like activity in the FST and TST in mice without affecting locomotor activity. It was also effective in the CMS model of depression. Furthermore, Rg1 up-regulated the BDNF signalling pathway in the hippocampus and down-regulated serum corticosterone level during the CMS procedure. In addition, Rg1 was able to reverse the decrease in dendritic spine density and hippocampal neurogenesis caused by CMS. However, Rg1 had no discernable effect on the monoaminergic system. CONCLUSIONS AND IMPLICATIONS Our results provide the first evidence that Rg1 has antidepressant activity via activation of the BDNF signalling pathway and up-regulation of hippocampal neurogenesis.     

Up- regulation of hippocampal neurogenesis is required in the antidepressant efficacy of agmatine

AIM： Accumulative studies demonstrate that exogenous administration of agmatine （AGM）, a new endogenous neurotransmitter, exerts antidepressant effect. The aim of this study is to explore the mechanism of chronic antidepressant efficacy of AGM. METHODS： Proliferation and neuronal phenotype differentiation of hippocampal progenitor cells in chronically stressed mice were measured by immunohistochemistry. Proliferation of cultured hippocampal progenitor cells from neonatal rats was determined by colorimetric assay （cell counting kit -8 ） and 3H -thymidine incorporation assay. The chronic antidepressant efficacy of AGM was evaluated by sucrose consumption test and novelty suppressed feeding test.