缺锌对大鼠学习记忆功能及其脑区生长抑素和加压素含量 …

目的和方法：本实验用避暗法检测锌对大鼠学习记忆的影响,并用放免法测定不同脑区生长抑素和加压素含量的变化,结果：缺锌使大鼠学习记忆功能明显降低,同时下丘脑,海马和皮层等脑组织生长抑素和加压素含量明显降低,缺锌后补锌可使大鼠学习记忆功能及其海马中生长抑素和加压素含量恢复到正常状况,结论：缺锌降低大鼠学习记忆功能与锌对脑组织尤其是海马内源性生长抑素和加压不代谢的调节有关。     

海马内生长抑素与γ—氨基丁酸在大鼠穿梭箱主动回避反应…

本实验以大鼠穿梭箱主动回避反应（ＡＡＲ）的习得和消退为学习记忆的指标,研究了海马内生长抑素（ＳＳ）和γ－氨基丁酸（ＧＡＢＡ）在学习记忆中的作用。结果如下：（１）经训练而建立了ＡＡＲ的大鼠,其海马内ＳＳ较对照组显著增高,而海马内ＧＡＢＡ含量去明显降低;（２）海马内注入ＳＳ的耗竭剂半胱胺使大鼠ＡＡＲ的习得受到明显损害,ＡＡＲ的消退显著加速,海马内ＳＳ明显降低,而ＧＡＢＡ含量去显著升高;（３）海马内注入     

海马内生长抑素与γ－氨基丁酸在大鼠穿梭箱主动回避反应中的作用

本实验以大鼠穿梭箱主动回避反应（ＡＡＲ）的习得和消退为学习记忆的指标,研究了海马内生长抑素（ＳＳ）和γ－氨基丁酸（ＧＡＢＡ）在学习记忆中的作用。结果如下：（１）经训练而建立了ＡＡＲ的大鼠,其海马内ＳＳ较对照组显著增高,而海马内ＧＡＢＡ含量却明显降低;（２）海马内注入ＳＳ的耗竭剂半胱胺（Ｃｙｓ,２０ｇ／Ｌ）使大鼠ＡＡＲ的习得受到明显损害,ＡＡＲ的消退显著加速,海马内ＳＳ明显降低,而ＧＡＢＡ含量却显著升高;（３）海马内注入ＧＡＢＡ（２００ｇ／Ｌ）使大鼠ＡＡＲ的消退显著加速的同时,其海马内ＳＳ含量亦显著降低。由此表明,海马内ＳＳ可能有促进学习记忆的作用,而海马内ＧＡＢＡ升高则有相反的效应;二者在海马调控学习记忆过程中具有重要作用。     

癫痫对大鼠学习记忆的影响及与生长抑素的相关性研究

对听源性癫痫大鼠进行迷宫训练,观察癫痫发作对大鼠光分辨学习作业的成绩以及用放射免疫分析法测定的大鼠部分脑区中生长抑素含量的影响。结果表明：（１）癫痫发作对大鼠记忆阶段有明显的抑制作用（Ｐ＜０．０１）;（２）癫痫发作后,在大鼠信息提取明显障碍的同时,其颞叶皮层、下丘脑、垂体及海马中生长抑素的含量明显增加（Ｐ＜０．０５－０．０１）。结果提示：癫痫发作影响大鼠学习记忆过程,在该过程中生长抑素含量发生改变。     

抑郁症模型大鼠学习记忆能力变化研究

为探讨抑郁症发生发展过程中学习记忆能力的变化模式及其可能机制．分别采用21天慢性非预见性刺激法和嗅球切除法建立的抑郁症模型大鼠．运用旷场行为实验（open—field behavior）检测大鼠主动性活动能力,用Morris水迷宫法检测大鼠空间学习记忆能力,HPLC—UV法测定大鼠血清皮质醇含量。电生理法记录海马CA1区LTP与LTD,观察海马神经元的突触可塑性。结果显示：与对照组相比,两种模型的自主活动性、空间探索兴趣和学习能力都明显降低,而记忆的反馈功能没有明显的变化。同时．两种模型大鼠海马神经细胞的突触可塑性显著下降,血清皮质醇的含量则明显上升。提示两种建模方法均导致大鼠产生抑郁症状和学习能力障碍．但对记忆反馈功能无明显影响。     

葛根素对血管性痴呆大鼠海马突触传递长时程增强的影响

目的：探讨葛根素对血管性痴呆大鼠长时程增强（LTP）的影响。方法：采用Morris水迷宫和LTP诱导法检测血管性痴呆模型大鼠空间学习记忆能力和海马突触传递的改变。结果：模型组大鼠不同时间点测得的Morris水迷宫逃逸潜伏期均较假手术组明显延长,海马LTP诱导率明显降低,而药物组大鼠EL均短于模型组,但LTP诱导率明显增强。结论：葛根素可增强血管性痴呆大鼠突触传递功能,改善其长期存在的学习记忆障碍。     

加压素对记忆的影响及其与海马中去甲肾上腺素和多巴胺的关系

采用海马内注射方法,探讨了精氨酸加压素对大鼠穿梭箱条件回避行为的影响及其与海马中去甲肾上腺素能末梢递质的关系;用高效液相色谱-电化学检测法研究了精氨酸加压素对海马中单胺类递质及其代谢产物含量的影响。结果显示:(1)两侧海马内注射精氨酸加压素(各50pg),可延缓动物条件回避行为的消退;(2)用6-羟多巴胺(各10μg)损毁两侧海马中的去甲肾上腺素能末梢,可阻断精氨酸加压素的促记忆效应;(3)精氨酸加压素可加速海马中去甲肾上腺素和多巴胺的消失。上述结果提示,加压素对记忆的易化作用,至少部分通过海马起作用;海马内的去甲肾上腺素能末梢可能参与加压素对记忆过程的调节;加压素的作用很可能是通过加强脑内去甲肾上腺素的降解代谢来实现的。     

心脑佳配方对慢性酒精中毒大鼠学习记忆及海马NMDA受体亚基NR2B表达的影响

目的：研究心脑佳配方对慢性酒精中毒大鼠学习记忆及海马N-甲基-D-天冬氨酸（NMDA）受体2B亚基（NR2B）表达的影响。方法：建立大鼠慢性酒精中毒模型,分别检测学习与记忆成绩、超氧化物歧化酶（SOD）活性和海马区NR2B mRNA表达。结果：学习记忆测试显示模型组大鼠学习记忆成绩比正常组明显下降（P〈0.01）,各用药组与模型组相比,学习记忆成绩明显上升（P〈0.05或P〈0.01）;模型组大鼠脑组织中SOD活性较正常组显著降低（P〈0.01）,而各用药组与模型组相比,脑组织中SOD活性显著升高（P〈0.05或P〈0.01）;PCR结果表明模型组大鼠海马区NR2B mRNA表达较正常组明显上升（P〈0.01）,各用药组与模型组相比,NR2B mRNA表达明显下降,差异有显著性（P〈0.01）。结论：心脑佳配方可能通过对NMDA受体亚基NR2B蛋白表达的调节而发挥抗酒精中毒作用。     

染料木素对卵巢切除大鼠学习记忆能力的影响

目的：探讨染料木素对卵巢切除大鼠学习记忆能力的影响及作用机制。方法：将40只SD雌性大鼠随机分为用假手术组、去卵巢对照组、染料木素高剂量、低剂量组、17β-雌二醇组,切除卵巢建立学习和记忆能力受损的模型。灌胃给药6周后Morris水迷宫测定各组大鼠学习记忆能力,免疫组化法观察大鼠海马微管相关蛋白（tau蛋白）阳性表达情况,测定大鼠脑组织中乙酰胆碱酯酶（AchE）、乙酰胆碱转移酶（ChaT）、超氧化物歧化酶（SOD）的活性及丙二醛（MDA）的含量,观察海马组织超微结构变化。结果：大鼠切除卵巢后Morris水迷宫测定的学习记忆能力显著下降,微管相关蛋白（tau蛋白）异常磷酸化阳性表达率增高,前脑皮质中超氧化物歧化酶（SOD）、乙酰胆碱转移酶（ChaT）活性降低,丙二醛（MDA）含量、乙酰胆碱酯酶（AchE）活性增高。低剂量的染料木素可以发挥类雌激素样作用,改善去卵巢大鼠的以上症状。结论：染料木素对卵巢切除导致的学习和记忆能力下降有改善作用,低剂量效果显著,其可能的机制是：抑制了脑内AchE的活性,使乙酰胆碱的降解减少;增强脑组织抗氧化能力;稳定微管相关蛋白（tau蛋白）,降低tau蛋白异常磷酸化水平。     

高脂膳食对肥胖易感和肥胖抵抗大鼠学习记忆能力的影响及机制

经过长期的高脂膳食后并非所有个体都会发生肥胖,还有些个体会产生肥胖抵抗现象。高脂膳食影响海马依赖的学习记忆等认知功能已被广泛证实,但目前关于高脂膳食对肥胖抵抗个体学习记忆能力影响的研究仍较少见。本文旨在对比研究高脂膳食对肥胖易感（obesity-prone, OP）和肥胖抵抗（obesity-resistant, OR）大鼠空间学习记忆能力的影响,并探讨其潜在的可能机制。Morris水迷宫结果显示,肥胖易感大鼠的学习能力显著低于对照大鼠和肥胖抵抗大鼠,但3组大鼠的记忆功能无显著性差异。Western印迹结果显示,与对照组相比,肥胖易感和肥胖抵抗大鼠海马内脑源性神经营养因子(BDNF)、血管内皮细胞生长因子(VEGF)和突触素(SYN)的含量均显著降低,丙二醛(MDA)和白介素1β(IL-1β)的含量均显著升高;且肥胖易感大鼠海马内上述蛋白质含量的变化更明显。免疫荧光染色和激光共聚焦显微镜扫描结果均显示,肥胖易感大鼠的海马神经发生水平显著低于肥胖抵抗大鼠和对照大鼠,但肥胖抵抗大鼠的海马神经发生水平与对照大鼠相比未见显著性变化。这些结果提示,高脂膳食可能是通过降低海马内突触可塑相关蛋白质的表达和神经发生,以及加剧炎症反应来损害肥胖易感大鼠的空间学习能力,而对肥胖抵抗大鼠的学习记忆能力影响不显著。     

慢性复合应激对大鼠学习和记忆及海马神经元神经颗粒素表达的影响

目的探讨慢性复合应激对大鼠学习和记忆功能及海马内神经元神经颗粒素(neurogranin,Ng)表达的影响。方法成年雄性Wistar大鼠随机分为对照组和复合应激组,复合应激组动物每天无规律交替暴露于复合应激原环境中,为期6周。应激结束后,用Morris水迷宫测试大鼠空间学习和记忆成绩,同时用免疫组织化学方法观察海马各亚区Ng表达的变化,并用RT-PCR技术分析各组大鼠海马Ng mRNA水平的变化。结果Morris水迷宫测试显示,应激组动物寻找隐蔽平台潜伏期明显短于对照组(P<0.05);应激组大鼠海马DG和CA3区Ng的蛋白表达水平明显高于对照组(P<0.05),而两组海马CA1区的Ng的免疫反应性无明显差别;与对照组相比,应激组动物的Ng mRNA水平亦明显上调(P<0.05)。结论慢性复合性应激大鼠的学习与记忆能力增强;Ng在海马中的表达和Ng mRNA转录水平增高,提示Ng参与了该增强机制。     

大鼠纹状体边缘区内神经降压肽和生长抑素免疫阳性反应的分布

用免疫组织化学方法研究了大鼠纹状体边缘区中神经降压肽和生长抑素免疫阳性反应的分布。神经降压肽和生长抑素免疫阳性纤维和胞体散在分布于纹状体中,但在边缘区中分布密集,形成一条明显的带,带的宽度和位置和边缘区一致。边缘区中可见神经降压肽和生长抑素免疫阳性胞体。本研究证明纹状体边缘区中存在密度较高的神经降压肽和生长抑素免疫阳性纤维和胞体,并推测和边缘区的学习记忆功能有关     

铅致大鼠记忆受损及海马AChE阳性纤维的改变

本实验采用明暗箱被动回避反应和穿梭箱条件性回避反应测定, 探讨了铅对大鼠学习与记忆的损害作用。应用酶组织化学方法观察了铅致大鼠海马的结构改变。行为测定显示, 大鼠饮１０％ 醋酸铅水液之前和之后, 其进洞潜伏期 （ｓｔｏｐｔｈｒｏｕｇｈ ｌａｔｅｎｃｙ, ＳＴＬ） 与对照组无明显差异, 而饮醋酸铅水液后, 其条件性回避反应率（ｃｏｎｄｉｔｉｏｎｅｄ ａｖｏｉｄａｎｃｅ ｒｅｓｐｏｎｓｅ ｒａｔｅ, ＣＡＲＲ） 较对照组明显下降（ｄ４－ ｄ１４, Ｐ＜ ００５）, 表明大鼠饮醋酸铅水液后长时记忆不受影响, 而短时记忆受到损伤。组织化学反应染色显示实验组海马腔隙分子层内ＡＣｈＥ阳性纤维面积百分数较对照组明显减少（Ｐ＜ ００５）, 且纤维变细, 膨体减少。推测铅致大鼠短时记忆能力下降, 可能与海马内胆碱能纤维减少有关。     

The Effect of Severe Zinc Deficiency and Zinc Supplement on Spatial Learning and Memory

Zinc deficiency during pregnancy and during lactation has been shown to impair cognitive function and motor activity in offspring rats. In the present study, the effect of zinc deficiency and zinc supplement on spatial learning and memory in Morris Water Maze (MWM) and motor activity in open field were investigated. Pregnant rats after mating were divided to three groups. Control group fed a standard diet and a zinc deficient (ZnD) group fed a diet deficient in zinc (0.5–1.5 ppm) and a zinc supplement (ZnS) group fed a standard diet and enhanced zinc in the drinking water (10 ppm). All the diets were exposed during the last trisemester of pregnancy and during lactation. Rat’s offspring in these groups were tested for spatial learning and memory in MWM at post natal day (PND) 56 and were tested for motor activity in open field at PND 66.The Escape Latency (EL) and Traveled Distance (TD) in the ZnD group were increased but Percentage of Time Spent in the target quadrant (PTS) was decreased compared to the control group. In addition, these were no significant differences in EL and TD, but PTS had significant increase in ZnS compared to the control group. In the open field, Total Distance Moved (TDM) and Time of Motor Activity (TMA) for the ZnD were decreased compared to the control group, but there were no significant differences in TDM and TMA between control and ZnS groups. These findings suggest that zinc deficiency during the last trimester of pregnancy and during lactation impaired spatial learning and memory in their offsprings and has also negative effect on motor activity. In addition, ZnS has a significant effect on spatial learning and memory but no effect on motor activity in their offsprings.     

Effects of Forced Running Exercise on Cognitive Function and Its Relation to Zinc Homeostasis-Related Gene Expression in Rat Hippocampus

Voluntary exercise has been implicated to be beneficial for overall health and cognitive function in both clinical and experimental studies, but little is presently known about forced physical exercise on cognition and underlying molecular mechanism. We have used real-time RT-PCR to analyze gene expression in hippocampus, in the presence and absence of physical exercise, during spatial learning of rats in the Morris water maze. Our results show distinct zinc homeostasis-related gene expression profiles associated with learning and memory. Rats with physical exercise (EXP) showed a significant up-regulation of mRNA expression of zinc transporter-2 (ZnT-2), ZnT-4, ZnT-5, ZnT-6, and ZnT-7, metallothionein-1 (MT-1)–MT-3, divalent cation transporter-1, and Zrt-Irt-like proteins-7 in hippocampus when compared with control rats. In addition, spatial learning ability was improved in EXP rats compared with that in control group. This study provides the first comparative view of zinc homeostasis-related gene expression in hippocampus following forced physical exercise. These results suggested that forced physical exercise may provide a simple means to maintain brain function and promote learning capacity. Results of this study also suggest that exercise mobilizes zinc homeostasis-related gene expression profiles that would be predicted to benefit brain plasticity processes.     

戊四氮点燃癫痫大鼠空间学习记忆改变及海马突触素、突触后致密物PSD-95表达的变化

目的探讨戊四氮点燃癫痫对大鼠空间学习记忆的影响及可能的分子机制。方法戊四氮(pentylenetet-razol,PTZ)点燃建立慢性癫痫(chronic epileptic,CEP)模型,Morris水迷宫进行行为学检测,免疫组织化学方法观察大鼠海马CA1、CA3区突触素(synaptophysin,P38)和突触后致密物95(postsynaptic density 95,PSD-95)的表达,并用计算机图像分析系统对免疫反应结果进行处理。结果水迷宫试验检测癫痫组大鼠空间学习记忆能力受损;免疫组化结果表明其海马CA1、CA3区P38和PSD-95免疫反应产物较对照组明显减少(P<0.01,P<0.05)。结论戊四氮点燃癫痫大鼠伴有学习记忆功能减退,其海马神经元P38和PSD-95的表达减少可能参与了空间学习记忆受损。     

Zinc homeostasis in the hippocampus of zinc-deficient young adult rats

On the basis of the evidence of the transient learning impairment of young adult rats fed a zinc-deficient diet for 4 weeks, zinc concentration in the hippocampus was examined in the zinc-deficient rats to understand the mechanism of brain dysfunction in zinc deficiency. Zinc concentration in the hippocampus, as well as that in other brain regions, was not decreased by 4-week zinc deprivation. When Timm's stain, with which histochemically reactive zinc in the presynaptic vesicles is detected, was compared between the control and zinc-deficient rats, the intensity of Timm's stain in the hippocampus was almost the same between them. In the hippocampus, zinc concentration in the synaptosomal fraction was not also decreased by 4-week zinc deprivation, whereas that in the crude nuclear fraction was significantly increased. These results suggest that zinc concentration in the presynaptic vesicles is not decreased in young adults rats by 4-week zinc deprivation. It is likely that zinc-requiring systems in the nucleus are more responsive to zinc deficiency than vesicular zinc. This responsiveness appears to be involved in the transient learning impairment.