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1.
目的通过哺乳期暴露邻苯二甲酸二(2-乙基己基)酯(di-2-ethylhexyl phthalate,DEHP),研究DEHP对子代SD雄性大鼠空间学习记忆能力和突触可塑性相关蛋白基因表达的影响,初步探讨其机制。方法成熟SD大鼠妊娠后随机分为溶剂对照组(橄榄油)、DEHP低剂量组(5 mg/kg BW)、中剂量组(50 mg/kg BW)和高剂量组(500mg/kg BW)。分娩后第1天至断乳,母鼠经口连续灌胃染毒21 d。待子代大鼠出生后第65~70天,进行Morris水迷宫测试;Real-Time PCR法检测海马突触可塑性相关蛋白基因mRNA的表达情况。结果 Morris水迷宫定位航行试验中,500 mg/kg BW剂量组潜伏期比对照组长,差异有统计学意义(P0.05);在空间探索试验中,500 mg/kg BW剂量组在目标象限路程百分比、目标象限停留时间百分比、穿越平台次数方面,与对照组相比有所降低,差异均有统计学意义(P0.05)。Real-Time PCR结果显示,暴露于50、500 mg/kg BW组雄性子代大鼠海马内突触可塑性相关蛋白基因PSD95、CREB、PKA、CAMKII mRNA表达水平下调(P0.05);500 mg/kg BW剂量组海马内突触可塑性相关蛋白基因BDNF mRNA表达水平下调(P0.05)。结论一定剂量DEHP哺乳期暴露,可影响子代大鼠的神经系统发育,对空间学习记忆能力造成损害。海马内突触可塑性相关蛋白基因PSD95、CREB、PKA、CAMKII、BDNF mRNA表达受到抑制,可能是其发生作用机制之一。  相似文献   

2.
目的 研究桂附汤对慢性不可预见性温和应激(chronic unpredictive mild stress,CUMS)小鼠抑郁模型的干预作用。 方法 利用CUMS法诱导C57BL/6小鼠抑郁模型,通过蔗糖偏好实验、旷场实验、悬尾实验观察桂附汤对小鼠抑郁样行为的影响,实时荧光定量聚合酶链式反应(Real-time PCR)检测小鼠海马组织脑源性神经营养因子(BDNF)mRNA 表达,免疫组化法(immunohistochemistry,IHC)检测小鼠海马区BDNF蛋白定位表达,苏木素-伊红(HE)染色观察海马组织形态学的变化。 结果 与对照组相比,模型组体质量下降,肾上腺指数升高,糖水偏好度显著降低,旷场实验总静止时间显著升高、进入中央区域次数显著降低,BDNF蛋白表达和mRNA水平显著降低;与模型组相比,桂附汤干预组肾上腺指数显著降低,糖水偏好度显著增加,旷场实验总静止时间显著降低、进入中央区域的次数显著增加,悬尾实验静止时间显著降低,海马BDNF mRNA及蛋白表达都显著增加,海马组织病理损伤明显改善。结论 桂附汤可改善CUMS诱导的小鼠抑郁样行为,上调BDNF表达,保护海马神经元的结构和功能。  相似文献   

3.
为了研究植物乳杆菌(Lactobacillus plantarum)ER135对利血平诱导抑郁小鼠的改善作用,选择6周龄雄性ICR小鼠,连续21 d灌胃植物乳杆菌ER135菌悬液(2.0×1010 cfu/mL),第22 d小鼠腹腔注射利血平(4 mg/kg)构建抑郁模型,通过小鼠行为学观察,血清和脑组织生化指标检测及海马组织蛋白表达变化,评价植物乳杆菌ER135对抑郁模型小鼠的改善作用。结果表明,饲喂植物乳杆菌ER135显著改善小鼠体温降低、眼睑下垂和运动能力下降等症状。与模型组相比,脑组织中5-羟色胺、多巴胺、去甲肾上腺素等神经递质的浓度分别提高了2.06 ng/L、1.42 pg/L、10.12 ng/L。降低血清炎症因子水平,肿瘤坏死因子以及白介素1β分别降低了9.40 ng/L和10.63 ng/L,同时还降低了氧化应激水平,与模型组相比差异显著(p<0.05,p<0.01)。海马组织Western-blot结果显示植物乳杆菌ER135明显增加抑郁小鼠海马组织神经营养通路中cAMP、CREB、BDNF等关键蛋白的表达。综上所述植物乳杆菌(Lactobacillus plantarum)ER135具有缓解利血平诱导抑郁的作用。  相似文献   

4.
该研究探讨了黑果腺肋花楸(黑果)果实、叶子的多酚调节抑郁小鼠模型的作用机理,旨在通过饮食干预达到调节抑郁的目的。注射4 mg/mL皮质酮构建小鼠抑郁症模型,采用行为实验、16S rRNA基因测序技术等对小鼠行为、肠道菌群组成与脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)的变化规律等进行研究。研究表明黑果多酚提取物可以显著改善抑郁症小鼠游泳、糖水偏好等行为,可将肠道菌群多样性水平升高至18.23%;使得大脑中BDNF水平可提高81.39%。黑果多酚提取物通过调控肠道菌群、大脑BDNF途径影响抑郁小鼠行为,改善抑郁状态,从而发挥抑郁调节作用,为黑果宽渠道深度开发提供了新支撑,高值化应用提供了理论指导,为饮食调理抑郁症提供新资源,也丰富了功能性食品类型和理论。  相似文献   

5.
本文研究了β-细辛醚快速抗抑郁作用,并对其不同给药方式的作用效果及潜在的生物学机制进行探讨。将70只昆明种雄性小鼠随机分为模型组(n=60)、正常组(n=10),模型组给予慢性不可预见性刺激,正常组常规饲养;21d后,采用糖水偏好实验选取40只造模成功小鼠,随机分成五组:β-细辛醚鼻腔组、β-细辛醚灌胃组、越鞠丸鼻腔组、越鞠丸灌胃组、模型对照组;正常组中随机选取8只小鼠作为正常对照组。单次给药30 min后依次进行旷场实验,悬尾实验和强迫游泳实验;采用Western blot实验检测给药后45 min小鼠海马区脑源性神经营养因子(BDNF)和酪氨酸激酶B(TrkB)蛋白的表达变化。β-细辛醚用药组的旷场实验得分高于模型对照组(p0.05);强迫游泳实验和悬尾实验中小鼠的静止时间更短(p0.05);与模型对照组比较,β-细辛醚用药组给药45 min后小鼠海马中的BDNF及其受体TrkB的表达均明显上调(p0.05)。β细辛醚具有快速抗抑郁作用,且这种潜在的快速抗抑郁作用可能与BDNF及其受体TrkB的激活相关。  相似文献   

6.
通过建立慢性轻度不可知应激刺激(CUMS)诱导的小鼠抑郁模型,研究当归挥发油对抑郁行为的影响及机制。小鼠随机分为正常组、模型组、低、中、高剂量当归挥发油组(15、30、60 mg/kg)及盐酸氟西汀组(2.1 mg/kg)。干预4周后发现,与模型组比较,当归挥发油各剂量组小鼠中央穿越次数、中央区活动时间及糖水偏好度升高(P<0.01),悬尾不动时间下降(P<0.05,P<0.01),海马CA1区病理变化减轻,血清白细胞介素-1β(IL-1β)、IL-6及肿瘤坏死因子-α(TNF-α)含量降低(P<0.01),而IL-10含量增加(P<0.01);除低剂量当归挥发油组小鼠脑组织多巴胺(DA)含量及神经营养蛋白-3(NT-3)表达无明显变化外(P>0.05),剩余各组小鼠DA、去甲肾上腺素(NE)、5-羟色胺(5-HT)含量及神经生长因子(NGF)、NT-3、脑源性神经营养因子(BDNF)表达均升高(P<0.05,P<0.01)。上述结果表明,当归挥发油具有改善CUMS诱导的小鼠抑郁行为作用,该作用与抑制神经炎症、上调单胺类神经递质含量及促进...  相似文献   

7.
建立慢性应激抑郁大鼠模型,采用ELISA法测定5-HT、NA、DA水平,ICH法测定BDNF、TrkB、pCREB、pERK的表达,评价三七叶总皂苷对脑内单胺及神经因子的影响。建模五周后,与空白组比较,模型组大鼠体重、糖水偏好率分别降低了17.43%、39.49%,自主活动表现为探索能力降低、趋避能力升高,海马体质量百分比显著减少,呈现出人类抑郁症中体重下降、快感缺失、自主活动下降、海马体萎缩等核心症状。而给药组与模型组比较,上述指标得到有效逆转。与模型组比较,三七叶总皂苷高剂量组(100 mg/kg)可以使脑内NA、DA水平分别升高13.89%及19.66%,而对5-HT水平没影响,并且使脑内BDNF、TrkB、pCREB、pERK的表达分别上升16.67%、47.83%、20.42%、22.84%,表明三七叶总皂苷具有良好的抗抑郁作用。  相似文献   

8.
该研究深入探讨“药食两用”中药党参、茯苓、甘草水提物改善学习记忆障碍小鼠的作用机制。小鼠随机分为正常组、模型组、党参-茯苓-甘草组(10、20、40 g/kg)和阳性药组(盐酸多奈哌齐,1.5 mg/kg),每组10只,不间断给药30 d(10 mL/(kg?d))。腹腔注射氢溴酸东莨菪碱建立学习记忆障碍模型(2 mg/kg,5 d),Morris水迷宫实验考察小鼠行为变化;ELISA检测小鼠海马组织中乙酰胆碱(acetylcholine,Ach)和乙酰胆碱脂酶(acetylcholinesterase,AchE)水平;Western blot测定胆碱能信号通路相关蛋白及磷酸化表达量。结果发现,与模型组比较,高剂量组(40 g/kg)小鼠在Morris水迷宫实验中穿过平台次数增加了5.48次,在第Ⅲ象限时间、路程分别增加了17.41%、14.39%;小鼠海马中ACh水平升高了26%,AChE水平降低了11.9%;中、高剂量组小鼠海马α7-nAChR、CaMK Ⅱ、p-ERK1/2、p-CREB蛋白表达明显增强。这表明党参-茯苓-甘草水提物能够对学习记忆障碍小鼠起到改善作用,其机制可能与激活海马组织胆碱能突触通路并上调相关蛋白的表达有关。该研究为潞党参、茯苓、甘草这三味“药食两用”中药资源改善学习记忆障碍功效提供研究基础,为开发山西省道地药材潞党参提供研究方向。  相似文献   

9.
本文研究了三七叶总皂苷的抗抑郁作用及其作用机制。40只大鼠随机分成空白组、模型组、氟西汀组和三七叶总皂苷中高剂量组,建立慢性应激抑郁大鼠模型评价三七叶总皂苷的抗抑郁活性以及对海马体cAMP、PKA、BDNF的影响。建模四周后,模型组大鼠与空白组比较,体重、糖水偏好率及自主活动水平等行为学指标分别降低了8.56%、22.48%、26.17%,表现出人类抑郁症中体重下降、快感缺失、自主活动下降等核心症状,而大鼠海马体cAMP、PKA、BDNF的水平分别降低了53.60%、53.60%、39.20%。给予三七叶总皂苷治疗后,与模型组相比,三七叶总皂苷高剂量组大鼠上述三个行为学指标分别增加了7.03%、26.21%、26.21%,上述三个生化指标也分别升高了41.29%、62.79%、49.05%。表明三七叶总皂苷能逆转抑郁大鼠行为学症状以及调节海马体cAMP、PKA、BDNF的水平。三七叶总皂苷具有良好的抗抑郁作用,其作用机制与调控海马体cAMP、PKA、BDNF水平有关。  相似文献   

10.
目的:探讨烟酰胺核糖(nicotinamide riboside,NR)作为一种营养补充剂对酒精暴露小鼠抑郁样行为及肠黏膜通透性的改善效果。方法:30只雄性C57BL/6J小鼠随机分为3组(10只/组),对照组和模型组每天给予0.2 mL生理盐水灌胃,NR干预组(NR组)每天给予400 mg/kg m_b NR灌胃。每周一至周四上午8时至下午16时给予模型组和NR组小鼠新鲜配制的体积分数15%乙醇水溶液自由饮用,下午16时至次日上午8时给予其自来水自由饮用;对照组小鼠全天给予自来水自由饮用,周五、六切断3组小鼠一切水源,周日给予3组小鼠自来水自由饮用。干预期间3组小鼠自由进食,实验持续10周。采用旷场实验、糖水偏好实验和强迫游泳实验评价小鼠抑郁样行为;苏木精-伊红染色观察小鼠海马组织CA1区病理学改变;酶联免疫吸附实验检测各组小鼠血清中脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)及脂多糖(lipopolysaccharide,LPS)质量浓度;采用透射电子显微镜对小鼠空肠和结肠组织细胞连接装置超微结构进行观察;采用示踪实验观察小鼠空肠和结肠组织渗透性;免疫印迹实验检测小鼠空肠和结肠组织中紧密连接蛋白occludin及ZO-1表达水平。结果:与对照组和NR组相比,模型组小鼠在旷场实验的总运动距离和中央区域停留时间缩短,糖水偏爱度明显下降,同时,强迫游泳实验中模型组不动时间达到(168.6±34.4)s,较对照组((107.9±47.4)s)显著延长(P0.05);NR干预后,其抑郁样行为较模型组明显改善。模型组小鼠海马CA1区出现部分神经细胞损伤,血清BDNF水平达到(438.9±46.7)pg/mL,较对照组((638.1±77.3)pg/mL)显著降低(P0.05);NR干预后,神经细胞损伤得到一定程度修复,血清BDNF水平达到(735.7±55.7)pg/mL,较模型组显著升高(P0.05)。模型组小鼠血清LPS水平达到(22.5±1.8)ng/mL,与对照组((13.2±3.0)ng/mL)相比显著升高(P0.05);其空肠和结肠黏膜上皮紧密连接和中间连接等细胞连接装置发生形态学异常改变;示踪实验结果显示,与对照组比较,模型组小鼠空肠和结肠组织渗透性增加;Western blot结果发现,与对照组比较,模型组小鼠空肠及结肠occludin、ZO-l蛋白表达水平均显著降低(P0.05)。NR干预后,小鼠血清LPS水平降低,达到(17.5±0.3)ng/mL,空肠及结肠组织渗透性及细胞连接装置得到明显改善和修复,occludin和ZO-l蛋白表达水平亦发生不同程度上调。结论:NR可有效缓解酒精暴露小鼠抑郁样行为,其作用机制可能与NR对酒精性抑郁小鼠肠黏膜通透性的修复作用有关。  相似文献   

11.
12.
In an effort to improve the quality of in vitro produced porcine embryos, we investigated the effect of brain-derived neurotropic factor (BDNF), a neurotropin family member, on in vitro maturation (IVM) of porcine oocytes. The expression of BDNF and truncated isoforms of its receptor, tyrosine kinase B (TrkB), and p75 common neurotropin receptor was detected in both follicular cells and metaphase-I stage oocytes by RT-PCR. However, mRNA of full-length TrkB was not found in oocytes although it was detected in follicular cells. The expression pattern of BDNF and TrkB was confirmed by immunohistochemistry. Supplementation with BDNF (30 ng/ml) during IVM significantly (P < 0.05) increased the first polar body extrusion and glutathione levels in oocytes, whereas the effect of BDNF on nuclear maturation was diminished when gonadotropin and epidermal growth factor (EGF) were added to the culture media. However, treatment with BDNF (30 ng/ml) along with EGF (10 ng/ml) in the presence of gonadotropin significantly (P < 0.05) increased the developmental competence of oocytes to the blastocyst stage after both in vitro fertilization (IVF; 29.1% when compared with control, 15.6%) and somatic cell nuclear transfer (SCNT; 13.6% when compared with control, 3%). This appeared to reflect a stimulatory interaction between BDNF and EGF to enhance the cytoplasmic maturation of oocytes to support successful preimplantation development. In conclusion, BDNFenhanced nuclearand cytoplasmic maturation of oocytes by autocrine and/or paracrine signals. Also, when used together with EGF, BDNF increased the developmental potency of embryos after IVF and SCNT, demonstrating an improved in vitro production protocol for porcine oocytes.  相似文献   

13.
Inflammation and oxidative stress play an important role in the pathogenesis of depressive disorders and nuclear erythroid related factor 2 (Nrf2), a regulator of RedOx homeostasis and inflammation, is a promising target for depression prevention/treatment. As fish oil (FO) and conjugated linoleic acid (CLA) are known Nrf2 inducers, their protective ability is comparatively evaluated in a murine model of depression (MRL/MpJ‐Faslpr). Oxidative stress, fatty acids content, and critical factors reflecting brain functioning—namely brain‐derived neurotrophic factor (BDNF), synaptic markers, and cholinergic signaling—are preliminarily evaluated in the frontal cortex of 8‐week (Young) and in 22‐week old animals (Old), which are used as model of depression. These markers are measured in Old mice at the end of a 5‐week pretreatment with FO or CLA (728 or 650 mg kg–1, respectively). Old mice exhibit disrupted Redox homeostasis, compensatory Nrf2 hyperactivation, lower docosaheaxaenoic acid (DHA), and lower BDNF and synaptic function proteins compared to Young mice. FO and CLA treatment relieves almost all the pathophysiological hallmarks at a level comparable to Young mice. Presented data provide the first evidence for the comparable efficacy of FO or CLA supplementation in preventing depression signs in Old MRL/lpr mice, likely through their ability of improving Nrf2‐mediated antioxidant defenses.  相似文献   

14.
研究鱼油对母鼠与新生大鼠海马组织中NR1、CREB、c-fos基因表达的影响。将64只成年SD大鼠随机分成阴性对照组和鱼油低剂量[150 mg/(kg·d)]、中剂量组[300mg/(kg·d)]和高剂量组[600 mg/(kg·d)],连续饲养60 d,使用实时定量PCR技术检测母鼠以及新生大鼠海马组织N-甲基-D-天门冬氨酸受体亚基(NR1)、即刻早期基因(c-fos)、cAMP反应元件结合蛋白(CREB)mRNA的表达。结果表明,与阴性对照组相比,鱼油低剂量组和中剂量组的母鼠与新生大鼠海马组织中NR1、CREB、c-fos基因的mRNA表达量显著提升,鱼油高剂量组母鼠与新生大鼠海马组织中NR1、CREB、c-fos基因的mRNA的表达量没有明显变化。孕期和哺乳期的饮食中添加一定剂量的鱼油,能够提高母鼠与新生大鼠海马组织中NR1、CREB、c-fos基因的表达。  相似文献   

15.
目的:探究火麻仁油及大麻二酚(Cannabidiol,CBD)对慢性不可预测的轻度应激(Chronic unpredictable mild stress,CUMS)模型小鼠行为学及炎症因子的影响。方法:将50只雄性C57BL/6小鼠随机分成5组:空白组、模型组、火麻仁油组(3 mL/kg)、CBD低剂量组(15 mg/kg)、CBD高剂量组(30 mg/kg),试验周期8周,测定小鼠抑郁、焦虑、学习认知能力及炎症因子(肿瘤坏死因子(TNF-α)、白细胞介素-1(IL-1β)和诱导NOS(iNos))的mRNA表达及小胶质细胞的离子化的钙结合衔接分子1(IBA-1)的蛋白表达。结果:与空白组相比,模型组在抑郁和焦虑行为及学习和认知功能有显著差异(P<0.05; P <0.01);与模型组相比,CBD剂量组均显著改善模型小鼠的抑郁焦虑行为并提高了学习认知功能(P<0.05; P<0.01),火麻仁油组显著改善小鼠的蔗糖偏好指数和新物体识别能力(P<0.05)。与空白组相比,模型组小鼠的皮层和海马组织中TNF-α、IL-1β和iNos mRNA表达量显著升高(P<0.05; P<0.01);与模型组相比,CBD剂量组的皮层和海马TNF-α、IL-1β和iNos mRNA表达量均显著降低(P<0.05; P<0.01);火麻仁油组皮层、海马TNF-α和iNos无显著性差异(P>0.05)。免疫组化结果显示,火麻仁油和CBD均抑制炎症介质小胶质细胞的离子化的钙结合衔接分子1(IBA-1)的表达。结论:CUMS小鼠建模成功,火麻仁油能够提高小鼠的抑郁行为及认知能力,并且降低IL-1β表达,CBD可改善小鼠的焦虑症状、提升学习和认知功能,抑制脑组织皮层和海马的炎症反应,从而证明火麻仁油和CBD对CUMS模型小鼠具有一定的作用。  相似文献   

16.
The ability of an oocyte to support early embryonic development requires both nuclear and cytoplasmic maturation. We have investigated the effects of brain-derived neurotrophic factor (BDNF) on maturation of the bovine oocyte and embryo development after parthenogenetic activation. By RT-PCR and immunohistochemistry, cumulus and oocytes were shown to express mRNA and protein for BDNF and the p75 common neurotrophin receptor. However, mRNA for the BDNF-specific full length and truncated isoforms of the TrkB receptor are only detected in cumulus, suggesting that oocytes and cumulus differ in their capacity to respond to neurotrophin signalling. In in vitro maturation experiments, the proportion of cumulus oocyte complexes maturing to metaphase II was not altered by BDNF in groups lacking fetal calf serum (FCS), but was significantly lower than the positive control containing 10% FCS (P < 0.01). However, after maturation, the proportion of parthenogenetically activated oocytes forming blastocysts was highest for 10 ng/ml BDNF (24%, n = 95) followed by 100 ng/ml BDNF (18%, n = 91) and 10% FCS (15%, n = 103), which in turn were greater than no serum (10%, n = 83; P < 0.01). Maturation in the presence of a BDNF blocking antibody resulted in a blastocyst yield that was comparable to the absence of serum, and lower than in the presence of BDNF (P < 0.01). Similar effects on progression to metaphase II and blastocyst formation were observed using oocytes matured without cumulus. Together, these results provide the first evidence for a role for neurotrophins in promoting oocyte cytoplasmic competence to support embryonic development, despite being insufficient in the absence of serum to enhance nuclear maturation.  相似文献   

17.
To observe the neuroprotective effects of marine collagen peptide (MCP) isolated from Chum Salmon (Oncorhynchus keta) skin by enzymatic hydrolysis, 20-month-old female C57BL/6J mice were fed with chow diet, 0.22%, 0.44% or 1.32% (wt/wt) MCP diet for 3 months. Comparing with aged control group, the abilities of passive avoidance and spatial memory and learning were significantly enhanced evaluated by step-down test and Morris water maze respectively. Furthermore, the abilities of learning and memory had no significant difference between 0.44% and 1.32% MCP treated groups and young control group. The alleviated oxidative stress, reduced apoptotic neurons, up-regulated expression of brain-derived neurotrophic factor (BDNF) and postsynaptic density protein 95 (PSD95) were observed in MCP treated groups compared with aged control group. Our research revealed that there were no significant difference between 0.44% and 1.32% MCP treated groups and young control group. These findings suggest that MCP could be a candidate for functional food to relieve memory deficits associated with aging.  相似文献   

18.
为了筛选出具有缓解抑郁作用的菌株,本研究以94株双歧杆菌为研究对象,以胆盐水解酶活性、抗生素耐性、抗逆性、粘附性作为益生菌评价的基本指标;以高产γ-氨基丁酸(gamma-aminobutyric acid,GABA)作为潜在抗抑郁症菌株的筛选指标;最后通过体外抑郁细胞模型试验,研究菌株对抑郁细胞模型的改善作用,进而评价菌株改善抑郁的潜力。结果显示:13株双歧杆菌的胆盐水解酶活性较高,且都不具有种属特异性耐性之外的抗生素耐性。耐酸耐胆盐实验证明:双歧杆菌ZT3、84和95都具有较高的抗逆性能;粘附结果表明:双歧杆菌91、92、95和98具有较强的粘附能力,粘附能力分别为:19.34、33.77、23.23、20.46 CFU/Cell。13株双歧杆菌产GABA能力检测结果显示,双歧杆菌98和95的GABA的产量较高,分别为285.0和232.8 mg/L。抑郁细胞模型试验结果显示:高、中、低剂量高产GABA的双歧杆菌98都具有缓解CORT诱导的细胞损伤的能力,而只有高剂量的双岐杆菌95可以缓解CORT诱导的细胞损伤。由于双歧杆菌98、95具有安全的抗生素耐受范围,较高的酸、胆盐耐受性和粘附能力以及高产GABA和缓解细胞模型损伤的能力,因此,其可以作为潜在的改善抑郁症状的菌株。  相似文献   

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