白松片对抑郁模型大鼠海马脑源性神经营养因子和酪氨酸激酶B表达的影响

目的采用慢性应激复制抑郁大鼠模型,观测白松片对抑郁模型大鼠海马BDNF、TrkB表达的影响,探讨白松片的抗抑郁作用机制.方法将大鼠随机分为正常组、模型组、白松片组、氟西汀组,采用连续21 d慢性轻度不可预见性应激配合孤养复制抑郁模型.运用免疫组化方法研究白松片对抑郁模型大鼠海马CA1、CA3区锥体细胞和齿状回颗粒细胞BDNF、TrkB蛋白表达的影响.结果与正常组相比,模型组大鼠海马CA1、CA3区和齿状回BDNF、TrkB免疫反应阳性神经元平均灰度值上升,分别为107.73±3.43、119.40±6.36、109.20±4.65;与模型组相比,白松片组大鼠海马CA1、CA3区和齿状回BDNF、TrkB免疫反应阳性神经元平均灰度值下降,分别为105.80±3.32、109.87±4.82、105.00±2.56.结论白松片增加抑郁模型大鼠海马BDNF、TrkB的表达,可能是其抗抑郁作用的分子机制之一.     

白松片对抑郁模型大鼠海马神经元睫状神经生长因子及其mRNA表达水平的影响

目的观测白松片对抑郁模型大鼠海马睫状神经生长因子(CNTF)及其mRNA表达水平的影响,探讨白松片的抗抑郁作用的机制.方法将大鼠随机分为正常组、模型组、白松片组、氟西汀组,采用连续21d慢性轻度不可预见性应激配合孤养复制抑郁模型.运用免疫组化和原位杂交方法探讨白松片对抑郁模型大鼠海马神经元细胞CNTF、CNTF mRNA表达的影响.结果白松片组大鼠海马神经元CNTF免疫反应阳性细胞数目增多,神经元平均灰度值降低,其中CA1区(105.14±7.21),CA3区(104.47±6.05),DG区(108.18±7.56);CNTFmRNA杂交阳性信号增加,神经元平均灰度值降低,其中CA1区(182.14±12.68),CA3区(176.82±11.12),DG区(175.98±12.15).与模型组比较,差异有显著性(P＜0.05或P＜0.01).结论白松片增加抑郁模型大鼠海马CNTF、CNTF mRNA的表达,可能是其抗抑郁作用的分子机制之一.     

白松片对抑郁模型大鼠海马神经元睫状神经生长因子及其mRNA表达水平的影响

目的观测白松片对抑郁模型大鼠海马睫状神经生长因子(CNTF)及其mRNA表达水平的影响,探讨白松片的抗抑郁作用的机制。方法将大鼠随机分为正常组、模型组、白松片组、氟西汀组,采用连续21d慢性轻度不可预见性应激配合孤养复制抑郁模型。运用免疫组化和原位杂交方法探讨白松片对抑郁模型大鼠海马神经元细胞CNTF、CNTFmRNA表达的影响。结果白松片组大鼠海马神经元CNTF免疫反应阳性细胞数目增多,神经元平均灰度值降低,其中CA1区(105.14±7.21),CA3区(104.47±6.05),DG区(108.18±7.56);CNTFmRNA杂交阳性信号增加,神经元平均灰度值降低,其中CA1区(182.14±12.68),CA3区(176.82±11.12),DG区(175.98±12.15)。与模型组比较,差异有显著性(P<0.05或P<0.01)。结论白松片增加抑郁模型大鼠海马CNTF、CNTFmRNA的表达,可能是其抗抑郁作用的分子机制之一。     

解忧方对抑郁大鼠模型海马BDNF及受体TRKB表达的影响

目的：观察中药解忧方对慢性应激抑郁模型大鼠海马BDNF、TrkB表达的干预作用。方法：建立慢性应激抑郁大鼠模型，采用免疫组化染色方法，观察解忧方对模型大鼠海马BDNF、TrkB表达的干预作用。结果：慢性应激抑郁模型大鼠海马BDNF、TrkB的表达明显低于正常组，解忧方能明显上调其表达。结论：解忧方能上调节BDNF、TrkB的表达，营养神经元，发挥抗抑郁作用。     

中药远志对慢性应激抑郁大鼠BDNF及其受体TrkB mRNA表达的影响

目的 探讨远志YZ-50对慢性应激大鼠脑源性神经营养因子BDNF及其受体TrkB mRNA表达的影响.方法 采用健康雄性Ⅱ级Wistar大鼠慢性应激抑郁模型,一步法抽提总RNA,分光光度计测光密度值.β-actin做内参照,RT-PCR技术检测BDNF及其受体TrkB mRNA在慢性应激大鼠海马组织的表达,从分子水平探讨在给予远志YZ-50后BDNF及其受体TrkB mRNA在慢性应激抑郁大鼠海马组织的变化规律.本实验共设5组,分别是空白对照、慢性应激模型组、地昔帕明、YZ-50低剂量组、YZ-50高剂量组.结果 YZ-50各剂量组均显示活性,能显著提高慢性应激抑郁大鼠海马区BDNF及其受体TrkBmRNA的表达,与模型组相比具有显著性差异.高剂量组作用最好,与模型组相比P<0.01.结论 YZ-50能够提高慢性应激抑郁模型大鼠海马区BDNF及其受体TrkBmRNA的基因转录,加强神经元营养,促进应激损伤的神经元恢复,从而改善应激抑郁模型大鼠的抑郁症状,有效发挥抗抑郁作用.     

永久性前脑缺血大鼠海马CA1区脑源性神经营养因子及其受体TrkB蛋白表达水平的改变

目的 探讨永久性前脑缺血大鼠海马CA1区脑源性神经营养因子(BDNF)及其受体酪氨酸蛋白激酶B(TrkB)蛋白表达水平的改变.方法 采用永久性结扎双侧颈总动脉的方法制造永久性前脑缺血大鼠模型.造模8周后对大鼠大脑石蜡切片进行免疫组织化学染色,测定海马CA1区BDNF以及TrkB的定位、相对定量表达.抽提大鼠海马CA1区组织蛋白,采用Western Blot对BDNF以及TrkB的蛋白表达水平进行定量分析.结果 永久性前脑缺血8周后,大鼠海马CA1区BDNF免疫反应阳性产物主要分布于锥体细胞的胞浆、胞核及轴突;模型组大鼠的BDNF蛋白表达水平显著升高(P＜0.05).大鼠海马CA1区TrkB免疫反应阳性产物主要分布于神经元的胞浆及轴突内;与假手术组相比,模型组大鼠海马CA1区TrkB蛋白表达水平无显著改变(P＞0.05).结论 双侧颈总动脉结扎造成的永久性前脑缺血可增加大鼠海马CA1区BDNF蛋白表达水平,而对其受体TrkB的蛋白表达水平无显著影响.     

逍遥散对抑郁模型大鼠海马中枢神经递质含量及BDNF和TrkB表达的影响

目的 探讨逍遥散对抑郁模型大鼠海马中神经递质(5-HT、NE、DA)的含量及海马脑源性神经营养因子(BDNF)和其受体型酪氨酸蛋白激酶B(TrkB)表达的影响,揭示逍遥散抗抑郁的机制.方法 将SD雄性大鼠50只随机分为正常组,模型组,盐酸氟西汀组(3 mg/kg),逍遥散高、低剂量组(14、7 g/kg).除正常组外,对其余各组大鼠进行56 d的孤养加慢性应激刺激,第29天起灌胃给药,连续给药28 d,给药结束后解剖大鼠取海马.采用放免法测定大鼠海马中神经递质5-HT、DA、NE的含量变化;采用免疫组化法检测海马中BDNF和TrkB阳性神经元面密度值的变化.结果 与正常组相比,模型组大鼠海马中5-HT、DA、NE的含量显著下降,BDNF和TrkB阳性神经元面密度值显著减小(P＜0.01),与模型组相比,逍遥散高、低剂量可以显著增加海马中5-HT、DA、NE的含量,明显提高BDNF和TrkB阳性神经元面密度值(P＜0.05或P＜0.01).结论 逍遥散可明显改善抑郁模型大鼠的抑郁状态,其机制与其可增加相关神经递质的含量,增强BDNF和TrkB表达有关.     

氟西汀对抑郁大鼠模型海马CA1区、CA3区及齿状回区神经生长因子表达的影响

目的:建立慢性温和不可预见性应激(CUMS)大鼠抑郁模型,研究氟西汀对CUMS大鼠海马CA1区、CA3区及齿状回区神经生长因子(NGF)表达的影响。方法:采用CUMS方法建立抑郁大鼠模型。氟西汀(3mg/kg)在造模完成后灌胃给药,每天一次,连续21d。旷场实验、强迫游泳实验检测大鼠行为学变化;免疫组化检测海马CA1、CA3及齿状回NGF的分布与表达。结果:与正常组相比,模型组大鼠水平运动和垂直运动减少(P<0.01),静止不动的时间较正常组增加(P<0.01)。海马CA1区、CA3区及齿状回区NGF表达强度低,阳性颗粒数目少,且着色浅淡。与模型组比较,氟西汀能明显改善CUMS大鼠的抑郁行为,增高CUMS大鼠海马NGF、细胞阳性表达。结论:抑郁大鼠海马NGF含量的高低与抑郁症的发生发展密切相关,促进海马细胞NGF蛋白的表达,保护神经的可塑性可能是氟西汀抗抑郁的机制之一。     

电针结合药物治疗对慢性应激抑郁模型大鼠海马CA1、CA3区BDNF的影响

目的研究电针针刺“百会”、“大椎”穴结合药物盐酸氟西汀对慢性应激抑郁症大鼠海马内CA1、CA3区脑源性神经营养因子(BDNF)的影响。方法将25只成年SD雌性大鼠随机分为正常组、模型组、电针组,药物组,针药结合组。以免疫组化技术显示比较电针结合药物、电针、药物对慢性应激抑郁模型大鼠海马CA1、CA3区BDNF的影响。结果电针结合药物组大鼠海马内CA1、CA3区BDNF阳性神经元的细胞数量表达多于电针组和药物组,而强阳性神经元的细胞数量表达少于电针组和药物组。结论电针结合药物治疗好于单纯药物治疗和电针治疗。     

急性高原低氧大鼠海马BDNF的表达

目的通过对平原组、急性高原组大鼠海马脑源性神经营养因子（BDNF）表达的研究，探讨高原低氧对大鼠脑海马神经细胞的损伤机制。方法应用免疫组织化学方法结合图像分析技术对两组大鼠海马BDNF表达进行定性、定量分析。结果急性高原组大鼠海马CA1、CA3区神经元BDNF阳性表达含量比平原组大鼠分别增高23．5％、24．1％。结论急性高原组大鼠海马CA1、CA3区神经元BDNF阳性表达发生明显变化，其含量升高，提示BDNF在避免急性高原低氧对大鼠海马CA1、CA3区神经元应激损伤中可能起重要作用。     

白松片对大鼠慢性应激抑郁模型的抗抑郁实验研究

目的：探讨慢性应激抑郁模型大鼠神经生化、神经内分泌的变化及白松片对其的干预作用。方法：60只SD雄性大鼠随机分为正常对照组（NC组）、模型对照组（MC组）、氟西汀对照组（FC组）和白松片治疗组（BST），每组15只。采用长期轻度不可预见性应激＋孤养复制大鼠抑郁模型，用高效液相色谱仪法检测海马5-羟色胺（5-HT）、谷氨酸（Glu）、γ-氨基丁酸（GABA）含量；放射免疫方法测定大鼠血浆促肾上腺皮质素释放激素（CRH）、促肾上腺皮质激素（ACTH）、皮质醇（CORT）的水平；应用逆转录聚合酶联反应方法测定大鼠下丘脑和大脑皮质CRH mRNA表达水平；免疫组织化学法测定海马脑源性神经营养因子、酪氨酸羟化酶的表达。结果：与NC比较，模型大鼠海马5-HT，GABA含量显著降低；血浆CRH，ACTH，CORT及海马Glu含量增加；脑内CRH mRNA表达显著升高（P〈0．01）；与MC组比，BST组和FC组大鼠海马5-HT，GABA含量升高（P〈0.01，或P〈0.05）；血浆CRH，ACTH，CORT及海马Glu含量降低；脑内CRH mRNA表达下降（P〈0．01）。结论：慢性轻度不可预见性应激可使大鼠神经内分泌、神经生化发生异常改变，白松片对此具有一定调节作用。     

小鼠海马内HDAC2的表达及其与NMDA受体、PSD-95的共定位

目的探讨组蛋白去乙酰化酶2(HDAC2)在成年C57BL/6小鼠海马内的分布及其与突触后致密区(PSD)蛋白成员的共定位,为揭示HDAC2与PSD蛋白复合物之间的内在联系及在海马相关的学习记忆过程中可能起到的调控作用提供形态学依据。方法应用免疫组化方法观察HDAC2在C57BL/6小鼠海马各区的表达分布。应用免疫荧光双标技术研究HDAC2与PSD蛋白成员N-甲基-D-天冬氨酸(NMDA)受体亚单位1(NR1)、PSD-95之间是否存在共定位。结果 HDAC2在小鼠海马CA1～CA3区锥体细胞和齿状回颗粒细胞均具有明显表达,而在各区的始层、辐射层、腔隙-分子层以及齿状回多形细胞层表达均较少。免疫荧光双标染色图片的重叠表明,HDAC2与NR1、PSD-95在小鼠海马CA1～CA3区锥体细胞层和齿状回颗粒细胞层内均可见显著共表达现象,其他区域偶见散在分布的双染神经元。结论 HDAC2在小鼠海马锥体细胞层和颗粒细胞层表达丰富,并与PSD蛋白成员间存在共定位现象。本实验结果为探讨HDAC2对谷氨酸能突触后神经元依赖的突触可塑性的调节机制提供了形态学依据。     

BDNF、TrkB在大鼠海马CA_3区的表达及其与学习记忆的关系

目的:研究BDNF及其受体TrkB在大鼠海马CA3区时空分布变化及其与学习记忆的关系。方法:采用免疫组织化学实验,观察BDNF及TrkB在正常大鼠发育期、成年期和老龄期海马CA3区的定位分布及时间变化。成年组和老龄组于免疫组织化学染色前接受水迷宫试验,研究BDNF及TrkB的分布变化与学习记忆的关系。结果:生后15~20d,海马CA3区阳性细胞最多。成年期细胞染色强,核大而圆无着色。老龄期阳性细胞数量少,染色淡,发生了明显退行性变化。水迷宫定向航行实验中平均潜伏期成年组和老龄组有显著性差异(P<0.01);空间搜索实验中NE象限停留时间成年组和老龄组有显著性差异(P<0.01)。结论:海马CA3区BDNF及TrkB的时空表达基本一致。表达高峰为生后15~20d。老龄期呈增龄性下降,细胞出现退行性变化。BDNF及受体TrkB的表达与学习记忆能力呈平行关系,BDNF及受体TrkB在学习记忆中发挥着重要作用。     

Effects of chronic multiple stress on learning and memory and the expression of Fyn, BDNF, TrkB in the hippocampus of rats

Background The effect of chronic stress on cognitive functions has been one of the hot topics in neuroscience. But there has been much controversy over its mechanism. The aim of this study was to investigate the effects of chronic multiple stress on spatial learning and memory as well as the expression of Fyn, BDNF and TrkB in the hippocampus of rats. Methods Adult rats were randomly divided into control and chronic multiple stressed groups. Rats in the multiple stressed group were irregularly and alternatively exposed to situations of vertical revolution, sleep expropriation and restraint lasting for 6 weeks, 6 hours per day with night illumination for 6 weeks. Before and after the period of chronic multiple stresses, the performance of spatial learning and memory of all rats was measured using the Morris Water Maze （MWM）. The expression of Fyn, BDNF and TrkB proteins in the hippocampus was assayed by Western blotting and immunohistochemical methods. The levels of Fyn and TrkB mRNAs in the hippocampus of rats were detected by RT-PCR technique. Results The escape latency in the control group and the stressed group were 15.63 and 8.27 seconds respectively. The performance of spatial learning and memory of rats was increased in chronic multiple stressed group （P〈0.05）. The levels of Fyn, BDNF and TrkB proteins in the stressed group were higher than those of the control group （P〈0.05）. The results of immunoreactivity showed that Fyn was present in the CA3 region of the hippocampus and BDNF positive particles were distributed in the nuclei of CA1 and CA3 pyramidal cells as well as DG granular cells. Quantitative analysis indicated that level of Fyn mRNA was also upregulated in the hippocampus of the stressed group （P〈0.05）. Conclusions Chronic multiple stress can enhance spatial learning and memory function of rats. The expression of Fyn, BDNF and TrkB proteins and the level of Fyn mRNA are increased in the stessed rat hippocampus. These suggest that Fyn and BDNF/TrkB signal transduction pathways may participate in the process of the enhanced learning and memory durina chronic multiple stress.     

慢性脑灌注不足老龄大鼠脑内BDNF的表达

目的探讨老龄大鼠慢性灌注不足后脑内脑源性神经营养因子(brain-derived neurotrophic,BDNF)的表达在血管性痴呆形成中的作用.方法采用Pulsinelli四血管阻断(4-vessel occlusion,4VO)改良法建立血管性痴呆大鼠模型,穿梭箱系统检测大鼠的学习记忆能力.应用免疫组化ABC法检测海马各区及额、颞叶皮层BDNF的表达.结果4VO 1周组海马CA1区BDNF阳性细胞数与对照组比较显著减少(P＜0.01),2周组、4周组仍进行性下降(P＜0.01),2月组与4周组无显著差异(P＞0.05).CAI区BDNF的表达与大鼠AAR成绩变化规律基本一致.3 d组额、颞叶皮层BDNF表达显著增加,1周组CA3、齿状回及颞叶皮层BDNF显著减少(P＜0.01),而后BDNF的表达无明显变化.结论慢性脑灌注不足老龄大鼠脑内BDNF表达的减少可能在血管性痴呆的形成中起重要作用.     

福尔马林痛模型中海马FOS的表达

目的 研究福尔马林诱发的大鼠海马原癌基因的表达。方法 注射福尔马林于大鼠左前爪掌心１ｈ后,采用免疫组化学方法,观察海马结构内ＦＯＳ免疫反应。结果 在海马结构观察到大量ＦＯＳ免疫反应细胞,主要见于下托,海马ＣＡ１,ＣＡ２／Ａ３和ＣＡ４区锥体细胞层以及齿状回内侧部和背侧部颗粒细胞层,齿状腹侧部偶见单个阳性细胞,除海马锥体细胞层和齿状回颗粒细胞层外,其它各层未见ＦＯＳ免疫反应细胞。结论 大鼠海马在福尔马     

帕罗西汀片对抑郁症大鼠模型抑郁行为的改善效果及相关作用机制分析

目的 分析帕罗西汀片对改善抑郁症大鼠模型抑郁行为的效果,同时对相关作用机制进行探讨。方法 选取健康雄性SD大鼠63只,并随机分为参照组(n=21)、试验组(n=21)及模型组(n=21)。正常饲养参照组大鼠,试验组大鼠及模型组大鼠在孤养及慢性轻度不可预见刺激条件下进行抑郁症大鼠模型构建,模型建立期间对试验组大鼠实施帕罗西汀灌胃操作,对模型组及参照组大鼠实施0.9%NaCl灌胃操作,分析帕罗西汀片对抑郁症大鼠自主活动次数、不动时间、记忆能力及学习能力大鼠海马CA3区TrkB、BDNF蛋白表达产生的影响。结果 试验组大鼠自主活动次数明显较模型组多,试验组及模型组大鼠自主活动次数均明显少于参照组大鼠,差异有统计学意义(P0.05)。Morris水迷宫定位航行实验结果显示,试验组大鼠潜伏期第1～4天均明显短于模型组,试验组、模型组Morris水迷宫空间探索实验穿台次数明显多于参照组,差异有统计学意义(P0.05)。免疫组化染色结果表明大鼠海马CA3区BDNF蛋白阳性着色为棕褐色,TrkB着色亦为棕褐色,与参照组及试验组相比,模型组阳性着色明显减少且染色强度明显下降。模型组大鼠TrkB及BDNF蛋白阳性细胞占比均显著低于参照组及试验组(P0.05);试验组大鼠TrkB及BDNF蛋白阳性细胞占比较参照组低,差异有统计学意义(P0.05)。结论 帕罗西汀片能够使抑郁症大鼠抑郁症状得到明显改善,同时还能使大鼠记忆能力以及学习能力得到提高,作用机制与海马CA3区TrkB及BDNF蛋白表达获得上调存在一定的相关性。     

Effects of unpredictable chronic stress on behavior and brain- derived neurotrophic factor expression in CA3 subfield and dentate gyrus of the hippocampus in different aged rats

Background Brain-derived neurotrophic factor （BDNF） is a stress-responsive intercellular messenger modifying hypothalamic-pituitary-adrenal （HPA） axis activity. The interaction between stress and age in BDNF expression is currently not fully understood. This study was conducted to observe unpredictable stress effect on behavior and BDNF expression in CA3 subfield （CA3） and dentate gyrus of hippocampus in different aged rats. Methods Forty-eight Wistar rats of two different ages （2 months and 15 months） were randomly assigned to six groups： two control groups and four stress groups. The rats in the stress group received three weeks of unpredictable mild stress. The depression state and the stress level of the animals were determined by sucrose preference test and observation of exploratory behavior in an open field （OF） test. The expressions of BDNF in CA3 and dentate gyrus of the hippocampus were measured using immunohistochemistry. Results Age and stress had different effects on the behavior of different aged animals （age： F=6.173, P〈0.05, stress： F=6.056, P 〈0.05）. Stress was the main factor affecting sucrose preference （F=123.608, P 〈0.05）. Decreased sucrose preference and suppressed behavior emerged directly following stress, lasting to at least the eighth day after stress in young animals （P 〈0.05）. The older stress rats showed a lower sucrose preference than young stress rats （P 〈0.05）. Older control rats behaved differently from the younger control animals in the OF test, spending more time in the central square （P 〈0.05）, exhibiting fewer vertical movements （P 〈0.05） and less grooming （P 〈0.05）. Following exposure to stress, older-aged rats showed no obvious changes in vertical movement and grooming. This indicates that aged rats were in an unexcited state before the stress period, and responded less to stressful stimuli than younger rats. There was significantly lower BDNF expression in the CA3 and dentate gyrus regions of the hippocampus following stress in both age groups （P〈0.05）, a reduction that was still present at the eighth day after stress （P〈0.05）. Stress and age were the main factors affecting the expression of BDNF （F=9.408, P 〈0.05; F=106.303, P 〈0.05）. The aged stress group showed lower BDNF expression compared to the young stressed group at every testing time point. Conclusion Stress has age-dependent effects on behavioral responses and hippocampal BDNF expression in rats.     

Effects of unpredictable chronic stress on behavior and brain-derived neurotrophic factor expression in CA3 subfield and dentate gyrus of the hippocampus in different aged rats

Background Brain-derived neurotrophic factor (BDNF) is a stress-responsive intercellular messenger modifying hypothalamic-pituitary-adrenal (HPA) axis activity. The interaction between stress and age in BDNF expression is currently not fully understood. This study was conducted to observe unpredictable stress effect on behavior and BDNF expression in CA3 subfield (CA3) and dentate gyrus of hippocampus in different aged rats. Methods Forty-eight Wistar rats of two different ages (2 months and 15 months) were randomly assigned to six groups: two control groups and four stress groups. The rats in the stress group received three weeks of unpredictable mild stress. The depression state and the stress level of the animals were determined by sucrose preference test and observation of exploratory behavior in an open field (OF) test. The expressions of BDNF in CA3 and dentate gyrus of the hippocampus were measured using immunohistochemistry. Results Age and stress had different effects on the behavior of different aged animals (age: F=6.173, P <0.05, stress: F=6.056, P <0.05). Stress was the main factor affecting sucrose preference (F=123.608, P <0.05). Decreased sucrose preference and suppressed behavior emerged directly following stress, lasting to at least the eighth day after stress in young animals (P <0.05). The older stress rats showed a lower sucrose preference than young stress rats (P <0.05). Older control rats behaved differently from the younger control animals in the OF test, spending more time in the central square (P <0.05), exhibiting fewer vertical movements (P <0.05) and less grooming (P <0.05). Following exposure to stress, older-aged rats showed no obvious changes in vertical movement and grooming. This indicates that aged rats were in an unexcited state before the stress period, and responded less to stressful stimuli than younger rats. There was significantly lower BDNF expression in the CA3 and dentate gyrus regions of the hippocampus following stress in both age groups (P <0.05), a reduction that was still present at the eighth day after stress (P <0.05). Stress and age were the main factors affecting the expression of BDNF (F=9.408, P <0.05; F=106.303, P <0.05). The aged stress group showed lower BDNF expression compared to the young stressed group at every testing time point. Conclusion Stress has age-dependent effects on behavioral responses and hippocampal BDNF expression in rats.     

Effects of unpredictable chronic stress on behavior and brain-derived neurotrophic factor expression in CA3 subfield and dentate gyrus of the hippocampus in different aged rats

Background Brain-derived neurotrophic factor (BDNF) is a stress-responsive intercellular messenger modifying hypothalamic-pituitary-adrenal (HPA) axis activity. The interaction between stress and age in BDNF expression is currently not fully understood. This study was conducted to observe unpredictable stress effect on behavior and BDNF expression in CA3 subfield (CA3) and dentate gyrus of hippocampus in different aged rats. Methods Forty-eight Wistar rats of two different ages (2 months and 15 months) were randomly assigned to six groups: two control groups and four stress groups. The rats in the stress group received three weeks of unpredictable mild stress. The depression state and the stress level of the animals were determined by sucrose preference test and observation of exploratory behavior in an open field (OF) test. The expressions of BDNF in CA3 and dentate gyrus of the hippocampus were measured using immunohistochemistry. Results Age and stress had different effects on the behavior of different aged animals (age: F=6.173, P <0.05, stress: F=6.056, P <0.05). Stress was the main factor affecting sucrose preference (F=123.608, P <0.05). Decreased sucrose preference and suppressed behavior emerged directly following stress, lasting to at least the eighth day after stress in young animals (P <0.05). The older stress rats showed a lower sucrose preference than young stress rats (P <0.05). Older control rats behaved differently from the younger control animals in the OF test, spending more time in the central square (P <0.05), exhibiting fewer vertical movements (P <0.05) and less grooming (P <0.05). Following exposure to stress, older-aged rats showed no obvious changes in vertical movement and grooming. This indicates that aged rats were in an unexcited state before the stress period, and responded less to stressful stimuli than younger rats. There was significantly lower BDNF expression in the CA3 and dentate gyrus regions of the hippocampus following stress in both age groups (P <0.05), a reduction that was still present at the eighth day after stress (P <0.05). Stress and age were the main factors affecting the expression of BDNF (F=9.408, P <0.05; F=106.303, P <0.05). The aged stress group showed lower BDNF expression compared to the young stressed group at every testing time point. Conclusion Stress has age-dependent effects on behavioral responses and hippocampal BDNF expression in rats.