石杉碱甲对电休克大鼠记忆、ARCmRNA及蛋白表达的影响

目的：研究石杉碱甲对电休克模型大鼠记忆和海马活性调节的细胞骨架联合基因（Activity-regulatedcytoskeletal—associatedgene,ARC）表达的影响。方法：大鼠随机分为假电休克对照组和电休克组,再随机分为生理盐水对照组（CS组、ES组）和石杉碱甲组（CH组、EH组）。第l-17天行生理盐水或石杉碱甲灌胃;第8—17天给予假电痉挛刺激或电痉挛刺激;第18天水迷宫定位航线实验;然后各组大鼠随机分成两组,一组取海马用RT．PCR检测ARCmRNA表达,Westem--blot法检测ARC蛋白表达水平,一组于48小时后行水迷宫空间位置探寻实验。结果：电休克导致大鼠显著记忆障碍,ARCmRNA、ARC蛋白表达水平较假电休克对照组显著下降;而石杉碱甲干预的电休克大鼠记忆保持较好,ARCmRNA、ARC蛋白表达水平显著高于生理盐水干预的电休克大鼠,与假电休克大鼠相比无显著性差异。结论：石杉碱甲能减轻电休克模型大鼠记忆损害,其机制可能与海马ARC的表达增加有关。     

电休克对大鼠空间记忆及海马p-ERK活性的影响

目的:观察电休克对大鼠空间记忆和海马磷酸化细胞外调节蛋白激酶(p-ERK)活性的影响。方法:大鼠随机分为电休克组和伪电休克组,每组12只。电休克组每天给予电痉挛刺激,伪电休克组每天给予假电痉挛刺激,共10天;第11天用水迷宫检测各组大鼠的空间学习记忆,然后每组大鼠再随机分为两组,每组6只。一组于学习后1小时处死取海马用Western blot法检测p-ERK活性,另一组于48小时后行水迷宫空间位置探寻实验检测大鼠的存储记忆。结果:电休克组的潜伏期显著长于伪电休克组(P0.01)。电休克组在隐匿平台周围区域/相反区域的搜寻时间无显著性差异(P0.05);伪电休克组在隐匿平台周围区域/相反区域的搜寻时间有显著性差异(P0.05)。电休克组海马p-ERK活性较伪电休克组显著下降(P0.01)。结论:电休克可导致大鼠显著空间记忆障碍,海马p-ERK活性的降低可能是其机制之一。     

β- 淀粉样多肽低分子量寡聚体对大鼠学习记忆功能的影响

目的:探究Aβ低分子量寡聚体对大鼠学习记忆功能的影响;方法:双侧海马内一次性注射Aβ低分子量寡聚体,15天后开始进行行为测试,测试方法采用跳台实验法、穿梭实验法和Morris水迷宫法;结果:跳台实验结果显示,与对照组比较,Aβ组跳台潜伏期短,错误次数多,差异有统计学意义(P<0.05);穿梭实验结果显示,与对照组比较,Aβ组由明箱进入暗箱的潜伏期短,错误次数多,差异有统计学意义(P<0.05);水迷宫实验结果显示,与对照组比较,Aβ组潜伏期长,跨越原平台次数少,差异有统计学意义(P<0.01);结论:Aβ组大鼠学习记忆能力和空间分辨能力降低,Aβ低分子量寡聚体在大鼠体内表现出较强的毒性作用。     

北京中医药大学基础医学院

目的:通过对更年期抑郁症模型大鼠行为学以及学习记忆的观察,探讨中药复方更逍遥冲剂的作用机制 方法:SD雌性大鼠40只,随机分为假手术组、更年期抑郁症模型组、中药中剂量组、中药大剂量组和西药对照组,观察开野实验中大鼠活动度、强迫游泳中大鼠的不动时间、以及通道式水迷宫检测大鼠学习记忆能力.结果:模型大鼠经过21d治疗后,开野实验水平积分、垂直积分明显增加,强迫游泳不动时间缩短,水迷宫实验游出时间缩短,错误次数减少.结论:更逍遥冲剂能够明显的改善更年期抑郁症大鼠的行为学评分,并具有改善其学习记忆能力的作用.     

2,6-二异丙基苯酚逆转嗅球切除抑郁模型大鼠电休克后的Tau蛋白过度磷酸化和认知障碍

通过观察2, 6-二异丙基苯酚对电休克后嗅球切除抑郁模型大鼠学习记忆和Tau蛋白过度磷酸化的影响,探讨兴奋性氨基酸受体拮抗剂对Tau蛋白过度磷酸化的调节及两者对抑郁大鼠学习记忆的影响,为改善学习记忆障碍的神经心理学机制研究和临床干预性治疗提供实验依据．按随机单位组2×2析因设计设置2个干预因素,即电休克干预(两水平：无处置、施行一个疗程电休克)和2, 6-二异丙基苯酚干预(两水平：腹腔注射5 ml 生理盐水或5 ml 2, 6-二异丙基苯酚100 mg/kg)的所有组合．选24周龄健康雄性Sprague-Dawley大鼠建立嗅球切除抑郁模型,将32只24周龄模型大鼠随机分为4个实验组(n=8):Ⅰ组(腹腔注射5 ml 2, 6-二异丙基苯酚100 mg/kg)、Ⅱ组(腹腔注射5 ml 2, 6-二异丙基苯酚100 mg/kg +施行电休克1个疗程)、Ⅲ组(腹腔注射5 ml 生理盐水)、Ⅳ组(腹腔注射5 ml 生理盐水+施行电休克1个疗程)．全部电休克处置结束24 h内开始Morris水迷宫检测,之后留取海马组织．高效液相色谱法检测神经递质谷氨酸(Glu)在海马组织中的含量;免疫组化SP法和蛋白质印迹法检测Tau-5(总Tau蛋白)、p-PHF1^Ser396/404、p-AT8^Ser199/202、p-12E8^Ser262、GSK-3β^1H8和PP-2A在海马组织神经元中的表达．电休克和2, 6-二异丙基苯酚均可造成大鼠学习记忆障碍,即延长逃避潜伏期并缩短空间探索时间,两者的影响呈相减效果．电休克可明显增加海马中神经递质谷氨酸(Glu)的浓度,2, 6-二异丙基苯酚可降低海马中神经递质Glu的浓度,且两者有相减效果．电休克和2, 6-二异丙基苯酚对海马总Tau蛋白和PP-2A蛋白的表达无明显影响．电休克可增加海马中磷酸化Tau蛋白和GSK-3β^1H8蛋白的表达;2, 6-二异丙基苯酚可减少海马中磷酸化Tau蛋白和GSK-3β^1H8蛋白的表达;两者的影响均呈相减效果．实验结果表明,电休克导致海马Glu浓度升高,通过上调GSK-3β^1H8增加海马Tau蛋白的磷酸化程度导致学习记忆功能障碍,而2, 6-二异丙基苯酚则可通过降低海马Glu浓度下调GSK-3β1H8的表达,从而减缓Tau蛋白的磷酸化程度以改善ECT后的学习记忆．     

慢性束缚应激对SD和Wistar大鼠学习记忆能力的影响

目的探讨慢性束缚应激对Wistar、SD两种品系大鼠学习记忆能力的影响,为应激模型中实验动物的选择提供依据。方法对两种品系大鼠(Wistar、SD)采用每天束缚10 h,束缚28 d建立慢性应激模型。采用物体认知新物体识别实验和Morris水迷宫空间学习、工作记忆行为学检测方法,观察束缚应激对两种品系实验动物学习记忆能力的影响。结果束缚28 d后,物体识别实验中,Wistar、SD模型组的辨别指数(discrimination index,DI)均低于对照组,但只有SD两组间差异存在显著性(P0.05);水迷宫空间学习阶段,SD模型组潜伏期高于对照组,第5天差异有显著性(P0.05),而Wistar模型组与对照组间的潜伏期没有差异;水迷宫工作记忆阶段,SD大鼠模型组与正常组比较,潜伏期显著增加(P0.05),Wistar模型大鼠的潜伏期与对照组比较没有显著差异。结论新物体识别实验和水迷宫实验,这两种反应动物不同学习记忆能力的行为学实验结果都表明,慢性束缚应激(10 h,28 d)对SD大鼠学习记忆能力的损伤较Wistar大鼠明显。SD大鼠可能更适合作为慢性应激所致学习记忆损伤动物模型。     

D-半乳糖致衰老模型大鼠的学习记忆和行为学观察及中药干预作用

目的观察D-半乳糖致衰老模型大鼠学习记忆能力和行为学情况,并探讨中药的干预作用。方法大鼠每日一次颈背部皮下注射5%D-半乳糖100 mg/kg。诱导大鼠衰老模型,连续7周,观察衰老模型大鼠的自主活动次数、空间记忆能力、主动回避遭受电击能力、探究活动等行为学表现和学习记忆能力,并用抗衰老片与首乌延寿片进行干预,观察中药的干预作用。结果皮下注射D-半乳糖造模后,衰老模型大鼠自主活动次数显著减少（P〈0.05,P〈0.01）,水迷宫试验探索路径长度和搜台潜伏期显著延长（P〈0.05,P〈0.01）,旷场试验移动路程长度和直立次数显著减少（P〈0.01）,穿梭回避试验平均潜伏期、进入错误区时间显著增加（P〈0.05,P〈0.01）。给予抗衰老片与首乌延寿片干预后,衰老大鼠的自主活动次数显著增加（P〈0.01）,水迷宫试验探索路径长度和搜台潜伏期显著缩短（P〈0.01）,旷场试验移动路程长度和直立次数显著增加（P〈0.01）,穿梭回避试验平均潜伏期、进入错误区时间显著减少（P〈0.05,P〈0.01）。结论D-半乳糖致衰老模型大鼠的自主活动次数减少,对新环境探索能力下降,学习记忆力下降;抗衰老片与首乌延寿片等中药可有效增强衰老模型大鼠的行为活动,提高衰老模型大鼠的学习记忆能力。     

绿茶多酚对脑缺血大鼠血脑屏障及学习记忆功能的影响

目的 研究绿茶多酚(Green tea polyphenols,GTPs)对脑缺血大鼠血脑屏障(Blood-brain barrier,BBB)及学习记忆功能的影响.方法 双侧颈总动脉结扎法制备脑缺血大鼠模型,大鼠随机分为假手术组、模型组和GTPs治疗组,每组8只,观察GTPs的保护作用.应用Morris水迷宫测试大鼠学习记忆能力,甲苯胺蓝染色法观察大鼠海马CA1区神经元形态变化,透射电镜观察BBB的变化以及海马CA1区神经元超微结构改变.结果模型组与假手术组相比BBB破坏,海马CA1区结构紊乱,学习记忆能力明显下降(P＜o.05),GTPs治疗组与模型组相比,缺血性脑损伤明显减轻,学习记忆能力明显改善(P＜0.05).结论 GTPs能够减轻缺血性脑损伤,从而发挥改善脑缺血SD大鼠学习记忆能力的作用.     

疏肝补肾法对疲劳大鼠的学习和记忆力之影响

目的:探讨疏肝补肾法对疲劳大鼠学习和记忆力及对海马CA1区神经颗粒素(Neurogranin,Ng)的mRNA表达变化的影响。方法:成年雄性Spargue-Dawley大鼠36只,随机分为模型组(MG)、对照组(CG)、和疏肝补肾组(LK)。采用复合模型:运动疲劳模型与睡眠剥夺法造疲劳大鼠模型。运用Y迷宫进行学习和记忆力的测试。以Real-timePCR技术分析海马CA1区神经颗粒素的mRNA表达。结果:Y迷宫实验显示用药后大鼠的学习和记忆能力优于模型组,而疏肝补肾组大鼠在正确反应率、错误反应次数、达标所需训练次数和总反应时间皆与模型组有差异(分别为P<0.01、P<0.01、P<0.05和P<0.05),其NgmRNA在海马CA1区的表达也显着高于模型组(P<0.01)。结论:复合模型会造成大鼠学习和记忆能力受损。疏肝补肾法能显着影响疲劳大鼠的学习记忆能力及海马CA1区Ng的mRNA表达。     

SHR、WKY大鼠与SD大鼠注意缺陷多动障碍模型行为学特征的比较

目的比较SHR、WKY、SD大鼠行为学特征,探寻研究SHR大鼠注意缺陷多动障碍(ADHD)理想的对照模型。方法运用旷场实验统计大鼠运动距离、运动速度、穿格数及理毛次数来评价SHR、WKY、SD大鼠自主运动情况;运用水迷宫实验检测三组大鼠的学习记忆能力。结果旷场实验结果显示,SHR大鼠在总运动量、平均运动速度及穿格次数上较WKY及SD大鼠均显著增加(P0.01);与WKY大鼠相比,SD大鼠运动距离显著高于WKY组(P0.01),其运动速度及穿格数略高于WKY组(P0.05);水迷宫隐匿站台实验中,与SHR大鼠相比,SD大鼠潜伏期较长(P0.05),在潜伏期运动距离上,SD大鼠在训练第1天、第3天及第4天运动距离较SHR大鼠延长(P0.05或P0.01);比较WKY组,SD大鼠潜伏期及潜伏期运动距离较WKY在各个训练时间均有不同程度的下降(P0.05或P0.01)。在空间探索阶段,SD大鼠穿台次数及目标象限运动时间、距离比率等均较SHR大鼠有所减少(P0.05),而较WKY大鼠则有不同程度的升高(P0.05或P0.01)。结论 WKY大鼠与SHR大鼠行为学差异过大,两者的比较存在一定的不足,增设SD大鼠作为SHR大鼠的对照组能够提升SHR大鼠行为学特征的可比性,更为客观的反映SHR大鼠的行为学特征。     

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。     

The effect of beta-(Tyr9)melanotropin-(9-18) on active avoidance behavior, electroconvulsive shock-induced amnesia and T-discrimination learning of rats

The effect of beta-(Tyr9)melanotropin-(9-18) was investigated on active avoidance behavior, electroconvulsive shock (ECS)-induced amnesia and T-discrimination learning in rats. The decapeptide inhibited the extinction of active avoidance behavior. It was also able to block ECS-induced amnesia if the treatment was performed immediately, or 4 hr or 20 hr after the ECS. In the T-discrimination paradigm the peptide facilitated spatial discrimination learning and reversal learning. These results suggest that beta-(Tyr9)melanotropin-(9-18) can influence learning and memory processes in different behavioral tests.     

Effects of leptin on memory processing

Leptin is a peptide hormone secreted by adipose tissue. Studies have shown that leptin crosses the blood-brain barrier (BBB) by a saturable transport system where it acts within the hypothalamus to regulate food intake and energy expenditure. Leptin also acts in the hippocampus where it facilitates the induction of long-term potentiation and enhances NMDA receptor-mediated transmission. This suggests that leptin plays a role in learning and memory. Obese mice and rats, which have leptin receptor deficiency, have impaired spatial learning. In disease states such as diabetes, humans and animals develop leptin resistance at the BBB. This suggests that low leptin levels in the brain may be involved in cognitive deficits associated with diabetes. In the current study, the effects of leptin on post-training memory processing in CD-1 mice were examined. Mice were trained in T-maze footshock avoidance and step down inhibitory avoidance. Immediately after training, mice received bilateral injections of leptin into the hippocampus. Retention was tested 1 week later in the T-maze and 1 day later in step down inhibitory avoidance. Leptin administration improved retention of T-maze footshock avoidance and step down inhibitory avoidance. Leptin administered 24 h after T-maze training did not improve retention when tested 1 week after training. SAMP8 mice at 12 months of age have elevated amyloid-beta protein and impaired learning and memory. We examined the effect of leptin on memory processing in the hippocampus of 4 and 12 months old SAMP8 mice. Leptin improved retention in both 4 and 12 months old SAMP8 mice; 12 month SAMP8 mice required a lower dose to improve memory compared to 4 months SAMP8 mice. The current results indicate that leptin in the hippocampus is involved in memory processing and suggests that low levels of leptin may be involved in cognitive deficits seen in disease states where leptin transport into the CNS is compromised.     

大鼠学习记忆能力与nov基因表达的关系

采用主动回避法进行大鼠学习记忆训练 ,选出学习成绩好和差的大鼠 ,用原位杂交、免疫细胞化学结合图像分析方法观察nov基因表达的差异。结果显示 ,novmRNA和NOV蛋白阳性神经元主要分布于海马、扣带皮质和联合皮质锥体层、基底神经节和下丘脑等脑区。好成绩组NOV蛋白免疫反应最强 ,阳性细胞最多 ,差成绩组nov基因的表达比假性条件反射组的表达稍强。novmRNA的表达在各组之间无明显的差异。以上结果提示 ,nov基因可能参与学习记忆的调控过程 ,这种调控发生在NOV蛋白翻译水平。     

The effect of a deficiency of the hormones of the peripheral endocrine glands on behavioral, learning and memory processes]

A comparative study of the effects of thyroid, adrenal, and gonadal deficit on capability for learning, retention of memory traces, and behavior was carried out in male rats under conditions of hormonal disbalance produced by extirpation of the endocrine glands. Behavior of animals was tested during the active and passive avoidance learning and in the open field. It was found out that the extirpation of the peripheral endocrine glands impairs learning and reproduction of the acquired reaction and alters the behavior. The results suggest that corticosteroid hormones take part in learning and behavior. Gonadal and thyroid hormones appear to exert a modulating influence on the higher nervous activity.     

大鼠脑发育不同时期学习记忆的变化及与NMDA受体通道动力 …

目的：研究大鼠脑发育不同时期学习记忆的变化及与ＮＭＤＡ受体通道动力学特性的关系。方法：采用学习记忆行为和离子通道动力学特性测定相结合的方法。结果：在爬杆主动回避反应中,发育早期大鼠习得和保持能力场明显强于成年大鼠。同时,发育早期大鼠训练后ＮＭ受体ｐＳ导电,而且３５ＰＳ通道开放时间和开放概率增加,３５ＰＳ通道长开放成份增多,有长ｃｌｕｓｔｅｒ开放而砀上大鼠２０Ｓ,３５ＰＳ通道关闭时间常数明显长于年龄     

The effect of newly synthesized psychotropic preparations on the "open field" behavior of rats]

The results of effect of some new synthesized psychotropic drugs of nootropic series on rats' behavior in "open field" are given. The increase of locomotive activity and decrease of emotional tension correlated with the rise of rats' ability to learning during working-out of avoidance reaction in shuttle-box, e.i. conditionally reflectory memory. It has been concluded that the study of dynamics of behavioral reactions in "open field" may be used for testing of new synthesized psychotropic drugs of nootropic series.     

Moderate prenatal carbon monoxide exposure produces persistent, and apparently permanent, memory deficits in rats

The effects of moderate (150 +/- 2 ppm) prenatal carbon monoxide (CO) exposure (maternal HbCO concentrations of 15.6 +/- 1.1%) on learning and memory were assessed in young and aged adult rats using a two-way active avoidance paradigm. In experiment 1, the prenatal CO-exposed rats at 120 days of age acquired a conditioned avoidance response equally well as control animals in a 100-trial session. However, following a 24-hr interval the CO-exposed rats failed to demonstrate significant retention of the task as indicated by the absence of significant improvement in performance over the indicated by the absence of significant improvement in performance over the previous day; control subjects did show significant retention. In experiment 2, in which 120-day-old animals received 50 training trials per day until a criterion of ten consecutive avoidance responses was met, the prenatal CO-exposed subjects again acquired the task as well as control animals. When tested for retention 28 days later, a significant memory impairment was again observed in terms of trials required to reattain the avoidance criterion as well as in total percent avoidance responding. In neither experiment did an analysis of initial or average latency to escape the footshock stimulus reveal any significant alterations. These latter results suggest that the observed performance impairment reflected a memory deficit and not a disruption of sensory, motor, or motivational factors. In experiment 3, prenatal CO-exposed rats approximately 1 year of age (300-360 days of age) showed impairment relative to air-exposed controls in both the original learning and retention of the two-way avoidance response. Again, however, there was no evidence for alterations in performance factors per se. Collectively these data indicate that while young adult rats prenatally exposed to 150 ppm CO demonstrate an associative deficit restricted to memory impairment, aged adults similarly exposed during the prenatal period display a more pronounced deficit similar to that recently reported for animals tested as juveniles. The importance of parametric manipulations in uncovering long-term toxicity is also discussed.