热应激对小鼠海马神经元的保护作用

本文观察了热应激预处理对脑缺血/再灌注昆明小鼠海马神经元的保护作用。实验采用昆明小鼠以双侧颈总动脉夹闭7min后再通制作脑缺血/再灌注模型,在缺血/再灌注前予以热应激预处理。根据不同的处理方法将动物随机分为四组:(1)正常对照组,(2)热应激预处理后缺血再灌注组(HS/IR),(3)缺血再灌注组(IR),(4)单纯热应激组(HS),后3组又分别分为1d、4d和14d三个亚组。水迷宫检测小鼠学习记忆的行为改变,免疫组织化学染色结合图像分析技术检测缺血/再灌注对海马CA1区神经元微管相关蛋白-2(MAP-2)的影响,Nissl染色计数CA1区神经元的数目。结果表明:与正常组、HS和HS/IR组比较,IR组小鼠水迷宫检测逃避潜伏期增加(P<0.01),其搜索策略以边缘式和限制式为主,而其它三组搜索策略则以趋向式和直线式为主。Nissl染色显示IR组和HS/IR组海马锥体细胞减少,且IR组细胞丢失比HS/IR组更多(P<0.05);MAP-2免疫组化染色显示4d时海马CA1区辐射层的树突发生紊乱和断裂,MAP-2有明显减少(P<0.05),14d时IR组MAP-2阳性表达主要聚集于胞浆中。以上实验结果提示,热应激预处理可以通过对海马神经元的保护作用改善动物脑缺血/再灌注引起的学习记忆能力的下降。     

热应激对小鼠海马CA1区神经元保护作用的机制

本文探讨热应激预处理对脑缺血小鼠海马神经元保护作用的可能机制。以72只6月龄昆明小鼠为研究对象,热应激预处理小鼠,随后夹闭双侧颈总动脉7min后再通制成脑缺血/再灌注损伤模型。根据不同的处理方法将动物随机分为四组:(1)正常对照组,(2)热应激预处理后缺血再灌注组(HS/IR),(3)缺血再灌注组(IR),(4)热应激组(HS)。将HS组、IR组和HS/IR组又分为1d、4d、14d3个亚组。用免疫组织化学及图像分析方法观察热应激对环磷酸腺苷反应元件结合蛋白(CREB)以及降钙素基因相关肽(CGRP)表达的影响。结果表明,与正常对照组比较,HS、HS/IR、IR组小鼠海马CREB表达明显增多(P<0.05)。热应激可诱导CGRP的分泌和在脑内的重分布,和其他组比较,CGRP在4dHS/IR组增多的最为明显(P<0.01)。热应激后,光镜下可见CGRP免疫阳性产物出现在海马CA1区的曲张纤维和神经元的核周质。以上实验结果提示,脑缺血状态下热应激的保护作用可能是通过激活信号蛋白CREB进而促进内源性保护物质CGRP释放而实现。     

环境富集对孕期应激大鼠青年期子代海马p-CREB 表达的影响

目的:检测环境富集对孕期应激子代海马磷酸化的环磷酸腺苷反应元件结合蛋白(p-CREB)表达的影响.方法:将SD孕鼠随机分为2组,一组动物不做任何处理,其子代断乳后在标准条件下喂养,为正常组;另一组动物在孕第13～19天接受限制性应激,其子代断乳后,一半在标准条件下喂养,构成应激组,另一半在子代环境富集条件下喂养(构成应激+环境富集组).子代在生后35d,用免疫组织化学和免疫印迹方法分别检测海马p-CREB的表达.结果:p-CREB阳性产物广泛表达于海马各区神经元.免疫印迹方法显示应激组p-CREB表达量明显少于正常组;应激+环境富集组海马p-CREB的表达量也明显多于应激组,与正常组的差别无统计学意义.结论:环境富集能有效逆转孕期应激导致的子代海马p-CREB表达下调.     

孕酮抗氧化作用对去卵巢小鼠学习记忆能力的影响

目的观察孕酮与小鼠学习记忆功能的维持和改善是否存在相关性,并探讨其机制。方法60只雌性昆明小鼠随机分为5组,除SHAM组外,其余各组小鼠行双侧卵巢切除术。术后对各组小鼠分别腹腔注射不同剂量孕酮或生理盐水。Morris水迷宫测试训练检测各组小鼠学习记忆能力,随后取脑,检测海马组织的SOD、MDA含量及T-AOC。结果OVX组在若干个测试训练时段其空间学习记忆能力显著较差,而孕酮各剂量组表现较好。海马组织SOD含量:SHAM组和孕酮各计量组均显著较高(P<0.05);MDA含量:SHAM组和HP组显著较低(P<0.05);T-AOC:SHAM组和HP组显著增高(P<0.05)。结论雌、孕激素的缺乏会引起成年雌性小鼠学习记忆能力下降,孕酮的长期补充治疗可以通过组织抗氧化作用,抵抗脂质过氧化反应,提高组织的抗氧化能力,来缓解或改善小鼠学习记忆功能障碍。     

气味对小鼠学习记忆能力及海马cAMP反应元件结合蛋白的影响

目的:探讨不同气味(苹果、香水、樟脑)对小鼠学习记忆能力及海马cAMP反应元件结合蛋白(CREB)和磷酸化的CREB(pCREB)的影响。方法:让小鼠在不同气味的环境下生活14d,在第7d开始方形水迷宫训练,3d后进行测试,连续测试5d。测试完后断髓处死动物,取出脑组织,用免疫组织化学染色观察海马pCREB和CREB表达情况,并进行图像分析。结果:樟脑组和香水组水迷宫的潜伏期较对照组延长,错误次数增多(P＜0.05)。免疫组化染色显示鼠海马CREB的磷酸化水平大大降低(P＜0.05),但对CREB的表达无明显影响。苹果组与对照组比各指标均无显著差异(P＞0.05)。结论:樟脑气味和香水气味对小鼠记忆能力有负面作用,且这种作用可能是通过降低CREB磷酸化水平而实现的。苹果气味对小鼠记忆能力无明显影响。     

慢性应激和急性吗啡暴露对不同年龄大鼠空间记忆的影响

目的：观察慢性应激和/或急性吗啡暴露（2mg／kg）对4周龄和10周龄大鼠记忆的影响。方法：建立平台应激模型，运用Morris水迷宫来观察慢性应激和急性吗啡暴露对4周龄和10周龄大鼠空间记忆的影响。结果：①4周龄组：吗啡组在目标象限停留的时间比对照组短（P〈0．05）。慢性应激及慢性应激加吗啡组与对照组相比差异无显著性（P〉0．05）。②10周龄组：慢性应激组、慢性应激加吗啡组在目标象限停留的时间均比对照组长（P〈0．05）。而吗啡组与对照组相比差异无显著性（P〉0.05）。③10周龄慢性应激组、吗啡组及慢性应激加吗啡组在目标象限停留的时间均比4周龄要长（P〈0．05）。而对照组在两个年龄段比较差异无显著性（P〉0．05）。两个年龄组中各组大鼠的运动速度分别与对照组相比差异无显著性（P〉0．05）。结论：①慢性平台应激对10周龄大鼠记忆起易化作用，对4周龄没有明显的影响。②急性吗啡暴露（2mg／kg）对4周龄大鼠的记忆有损害作用，而对10周龄的记忆没有影响。③慢性应激加吗啡对4周龄大鼠的记忆无影响，对10周龄大鼠的记忆有易化作用。     

磷酸化环磷酸腺苷反应元件结合蛋白在小鼠海马发育中的表达

目的:观察胚龄(E)18 d以及生后日龄(P)为1、3、7、14、21 d和28 d的小鼠海马磷酸化的cAMP反应元件结合蛋白(pCREB)的分布,从而为深入研究海马发育机制提供基础实验依据。方法:取E 18 d、P 1 d、P 3 d、P 7 d、P 14 d、P 21 d和P 28 d的小鼠胎鼠和仔鼠海马组织。利用免疫组织化学、免疫印迹结合图像分析技术对pCREB的表达变化进行系统的定性和定量分析。结果:免疫组织化学检测显示,pCREB主要表达在海马阿蒙角锥体细胞层和齿状回颗粒细胞层神经元的细胞核中。E 18 d,海马pCREB阳性细胞稀疏,染色浅,光密度低;E 18 d~P 7 d,pCREB阳性细胞逐渐密集,染色逐渐加深,光密度逐渐增高,P 7 d达高峰。P 14 d~P 21 d,pCREB阳性细胞密集程度逐渐降低,染色逐渐变浅,光密度逐渐降低;P 28 d表达与P 21 d相近,趋于稳定。免疫印迹检测显示,E 18 d~P 7 d,pCREB表达逐渐增高,P 7 d达高峰;P 14 d~P 21 d,表达逐渐降低,P 28 d表达稳定。结论:pCREB与小鼠海马发育有关,pCREB可能参与了小鼠海马发育中的细胞增殖。     

急性应激和急性吗啡暴露对不同年龄大鼠空间记忆的影响

目的：观察急性应激和／或急性吗啡暴露（2mg／kg）对4周龄和10周龄大鼠记忆的影响。方法：建立平台应激模型．运用Morris水迷宫来观察急性应激和急性吗啡暴露对4周龄和10周龄大鼠空间记忆的影响。结果：①4周龄组：急性应激组、吗啡组及急性应激加吗啡组在目标象限停留的时间均比对照组短（P〈0．05）。②10周龄组：急性应激组在目标象限停留的时间比对照组短（P〈0．05）。吗啡组及急性应激加吗啡组与对照组相比差异无显著性（P〉0．05）。③两个年龄段的比较：10周龄吗啡组、急性应激加吗啡组在目标象限停留的时间均比4周龄要长（P〈0．05）。而急性应激组和对照组这两个年龄段分别比较差异无显著性（P〉0．05）。两个年龄组中各组大鼠的运动速度分别与对照组相比差异无显著性（P〉0．05）。结论：①急性平台应激损害4周龄和10周龄大鼠的记忆，但没有明显年龄差异；②急性吗啡暴露（2mg/kg）对4周龄大鼠的记忆有损害作用，而对10周龄的记忆没有影响，存在年龄差异。③急性应激加吗啡损害了4周龄大鼠的记忆保持，而对10周龄大鼠的记忆保持无影响，存在年龄差异。     

电针对海洛因成瘾大鼠学习记忆及海马CREB表达的影响

目的：探讨电针对海洛因成瘾大鼠学习记忆的影响及作用机制。方法130只Wistar大鼠随机分为对照组、海洛因成瘾组（简称成瘾组）和海洛因成瘾后作电针治疗组（简称电针组）。进行跳台实验测试大鼠学习记忆能力,并用免疫组化方法检测鼠脑海马环磷酸腺苷反应元件结合蛋白（CREB）和磷酸化CREP（P—CREB）的表达。结果：成瘾组大鼠学习记忆下降（P％0．01）,电针组大鼠学习记忆有所改善（P〈0．01）;成瘾组大鼠海马CREB、P—CREB表达较对照组增高（P〈0．05）,电针组更高（P〈0．01）。结论：电针治疗可在一定程度上对抗海洛因成瘾大鼠所致的学习记忆下降,其机制可能与海马内CREB、P—CREB表达变化有关;CREB、PCREB参与学习记忆及海洛因成瘾的形成。     

慢性复合性应激对大鼠学习和记忆影响及海马中CaMKⅡCaMmRNA和CREBmRNA水平的变化

目的探讨慢性复合应激对大鼠学习与记忆的作用,以及Ca2 /钙调蛋白依赖性蛋白激酶Ⅱ(CaMKⅡ)、钙调蛋白(CaM)mRNA、环腺苷酸反应元件结合蛋白(CREB)mRNA水平的变化及其在学习和记忆中的作用。方法Wistar大鼠被随机分为慢性复合应激组(16只)和对照组(16只)。慢性复合应激组动物给予6周的慢性复合应激刺激,制备慢性复合应激模型;Morris水迷宫和Y迷宫测试大鼠空间学习和记忆的行为表现;免疫组织化学、Western blotting和RT-PCR检测大鼠海马CaMKⅡ、CaM mRNA和CREB mRNA水平的变化;观察分析CaMKⅡ在海马CA1和CA3区的分布和表达;电镜观察海马CA3区突触间隙的宽度和突触后致密物质(PSD)的厚度的变化。结果慢性复合应激6周后,应激组大鼠的学习与记忆能力均高于对照组(P<0.05,P<0.01);应激组海马CA3区突触间隙的宽度为5.0580±1.4216,PSD的厚度为20.9547±2.5693。与对照组相比,海马CA1和CA3区辐射层和始层CaMKⅡ的免疫染色明显增强,特别是始层;CaMKⅡ、CaM mRNA及CREB mRNA水平均明显增高(P<0.05,P<0.01)。结论慢性复合性应激后,大鼠的学习与记忆能力增强;海马CaMKⅡ、CaM mRNA和CREB mRNA水平增加可能是参与了慢性复合应激性学习记忆增强的机制。     

Acupuncture prevents cognitive deficits and oxidative stress in cerebral multi-infarction rats

The aim of this study is to investigate the effects of acupuncture on cognitive deficits and oxidative stress in cerebral multi-infarction rats. The results showed that acupunctural treatment attenuated memory impairment induced by cerebral multi-infarction, as evaluated by shortened escape latency and increased swimming time of rats with memory impairment in the target quadrant. The data additionally suggested that acupunctural treatment ameliorated oxidative injuries induced by cerebral multi-infarction by increasing the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the hippocampus. Further investigation by in situ hybridization and immunohistochemistry revealed that acupunctural treatment significantly increased the expression of CuZnSOD mRNA and protein in the hippocampus of the impaired rats. The findings demonstrate that acupuncture can exert beneficial effects on spatial memory and antioxidant status of cerebral multi-infarction rats.     

吗啡成瘾小鼠对正常小鼠学习记忆力能力的影响

目的:用BALB/C小鼠建立动物模型,观察吗啡成瘾戒断小鼠对其周围的正常小鼠学习记忆能力的影响。方法:将吗啡成瘾戒断小鼠与正常小鼠同笼饲养,然后用Morris水迷宫实验测定正常小鼠的学习记忆能力,应用RT-PCR的方法检测正常小鼠海马中PKCa、GABA分子表达的变化。结果:水迷宫实验证明,与生理盐水组相比,实验组小鼠的学习记忆能力明显降低(P<0.05),海马中PKCa和DABA的表达都明显升高(P<0.05)。     

The effect of chronic administration of l-arginine on the learning and memory of estradiol-treated ovariectomized rats tested in the morris water maze

OBJECTIVE:

The present study was carried out to evaluate the effect of l-arginine on the learning and memory of estradiol-treated ovariectomized (OVX) rats.

METHODS:

Forty-eight rats were divided into six groups: (1) sham, (2) OVX, (3) sham-Est, (4) OVX-Est, (5) sham-Est-LA, and (6) OVX-Est-LA. The animals of the sham-Est and OVX-Est groups were treated by weekly injection of estradiol valerate (2mg/kg). The sham-Est-LA and OVX-Est-LA groups were treated in the same manner but with an additional daily injection of l-arginine (200mg/kg). After eight weeks, animals of all groups were tested in the Morris water maze. The escape latency and path traveled to reach the platform were compared between groups.

RESULTS:

Time latency and path length in the OVX group were significantly higher than in the sham group (P<0.05). The OVX-Est group had a significantly shorter traveled path length and time latency compared to the OVX group (P<0.001). Time latency and path length in the sham-Est group was significantly higher than in the sham group (P<0.001). Time latency and path length in the OVX-Est-LA group were significantly higher than in the OVX-Est group.

CONCLUSIONS:

These results allow us to propose that chronic treatment with estradiol enhances the spatial learning and memory of OVX rats, and that long term l-arginine treatment attenuates the effects of improvement produced by estradiol in OVX rats.     

Glucosamine alleviates scopolamine induced spatial learning and memory deficits in rats

Introduction and objectiveBeneficial effects of glucosamine in spatial learning and memory impairment induced by scopolamine has been evaluated in rats by using Morris water maze.MethodsMale Wistar rats were randomly divided into control, scopolamine and scopolamine plus glucosamine groups. All injections were given in 5 consecutive days and 30 min after each injection, the rats were tested in the Morris water maze test. Escape latency and path length to reach the hidden platform were subjected to analysis of variance [ANOVA].ResultsThe rats treated with scopolamine showed increased escape latency and path length to reach the hidden platform compared to control group (P < 0.001). Both escape latency and traveled path length to reach the hidden platform in glucosamine treated animals (1 and 2 g/kg) were significantly lower (P < 0.05 to P < 0.001) than in the scopolamine group.ConclusionThe results of this study showed that the glucosamine can inhibit scopolamine-induced impairments of spatial learning and memory in rats. Glucosamine might offer a promise in either the prevention or the treatment of neurodegenerative diseases such as Alzheimer's disease.     

宫内缺氧对新生小鼠额叶皮质神经元内nNOS表达及对成年小鼠学习记忆能力的影响

为探讨孕鼠宫内缺氧对新生小鼠发育时期额叶皮质神经元内nNOS表达及对成年小鼠学习记忆能力的影响,本研究采用Tapanainen建立的缺氧模型致胎龄13、15、17d小鼠宫内缺氧,然后采用Nissl染色观察新生鼠发育时期P1、P7、P14、P28、P90额叶皮质内神经元的数量和形态变化;免疫组织化学染色方法观察新生鼠发育时期P1、P7、P14、P28、P90脑组织内nNOS阳性神经元的表达;Morris水迷宫实验检测P90小鼠的学习和记忆能力。结果显示:与正常组比较,宫内缺氧组小鼠额叶皮质神经元数量明显减少,额叶皮质神经元内nNOS的表达明显减弱。宫内缺氧组小鼠逃避潜伏期延长及穿环次数明显减少。以上结果提示宫内缺氧可导致新生鼠额叶皮质神经元数量明显减少及nNOS的表达也明显减弱,并引起成年小鼠学习记忆能力降低。     

Effects of treadmill running on spatial learning and memory in streptozotocin-induced diabetic rats

Previous studies have shown an association between diabetes mellitus and impairments in learning and memory. These deficits were partially reversed by the use of insulin. Due to the fact that exercise has positive effects on many physiological systems, including the central nervous system, the present study, evaluated the effects of treadmill running on spatial learning and memory in streptozotocin (STZ)-induced diabetic rats. The exercise program was treadmill running at 17 meters per minute (m/min) at 0° inclination for 40 minutes per day (min/day), 7 days/week, for 12 weeks. Experimental groups were: the control-rest, the control-exercise, the diabetes-rest and the diabetes-exercise. Spatial learning and memory was investigated by Morris water maze test in the rats after 12 weeks of diabetes induction and the exercise period. Our data showed that spatial learning and memory was significantly impaired in the diabetes-rest group with respect to the control-rest group. However, there were no differences between the other groups. The present results suggest that spatial learning and memory is affected under diabetic conditions and that treadmill running prevents these effects. The data correspond to the possibility that treadmill running is helpful in the prevention and alleviation of the cognitive decline in diabetes mellitus.     

虾青素提高血管性痴呆小鼠学习记忆能力

目的 探讨腹腔给药虾青素对于血管性痴呆(VaD)小鼠学习记忆能力的影响及其作用机制.方法 采用双侧颈总动脉夹闭法建立小鼠VaD模型后随机分成假手术组、模型组、虾青素低剂量组及虾青素高剂量组,分别给予相应形式的药物治疗.Morris水迷宫观察各组小鼠的学习记忆及空间探索能力,尼氏染色、免疫组织化学染色、Western b...     

Ghrelin对小鼠空间记忆和海马神经元突触及生长激素促分泌素受体表达的影响

目的 探讨Ghrelin对正常小鼠空间学习记忆能力和海马神经元突触及生长激素促分泌素受体（GHS-R）表达的影响。方法 8周龄小鼠 20只,随机分为实验组和对照组,分别腹腔注射Ghrelin和等量生理盐水,通过水迷宫实验检测小鼠的空间学习记忆能力,免疫组织化学实验检测海马Ghrelin受体GHS-R表达,并通过电子显微镜观察海马突触的超微结构变化。结果 水迷宫隐匿平台实验中,第2、3、4天,实验组小鼠的逃避潜伏期与对照组相比明显缩短（P <0.05）,跨越平台次数明显增加(P <0.05）,海马CA3和齿状回区GHS-R免疫阳性产物表达明显增强（P <0.05）,神经元突触数量明显增加（P <0.05）。结论 Ghrelin可能通过结合GHS-R,增加海马神经元突触数量,显著改善小鼠的空间学习记忆能力。