Effects of ACE-inhibitors on learning and memory processes in rats

INTRODUCTION: Besides their well known effect on systemic blood vessels and heart, ACE inhibitors are supposed to have an effect on CNS by changing the local peptide-protein system. AIM: To study the effect of ACE-inhibitors on learning and memory processes using active and passive avoidance. MATERIAL AND METHODS: Male Wistar rats were used; the animals were divided into 4 groups of 20 animals each. Distilled water (group C), captopril 1.5 mg/kg (group E1), trandolapril 2 mg/daily (group E2), and oxiracetam 0.1 mg/kg (group E3), respectively, were given orally 60 minutes before the test. Active (shuttle box) and passive (step-through) avoidance tests with standard configuration were used. RESULTS: The experimental and control animals increased the number of avoidances during the learning session of the active avoidance test; groups C, E1 and E2 showed no change in the number of escapes and intertrial crossings; in group E3 animals both variables were decreased. In memory retention test the experimental animals increased the number of avoidances in comparison to the controls. No difference was found in the number of escapes and intertrial crossings. In passive avoidance test all animals showed prolonged latencies during the learning session. In the early and late retention test prolonged latencies were found only in the experimental animals. CONCLUSION: The ACE inhibitors captopril and trandolapril improve learning and memory in active and passive avoidance tests comparable to the effect of the nootropic drug oxiracetam.     

百草枯对发育中小鼠学习记忆能力的影响

目的 探讨百草枯对发育中小鼠学习记忆能力的影响及可能的氧化损伤机制.方法 80只健康21 日龄断奶未成熟昆明种小鼠随机分为低、中、高剂量百草枯染毒组和对照组(四蒸水),每组20只,百草枯染毒剂量分别为0.89、2.67、8.00mg/kg,经口灌胃(1次/d),连续染毒28 d.采用Morris水迷宫和避暗穿梭实验测定小鼠学习记忆能力,微孔板比色法测定血清和海马组织中丙二醛(MDA)含量、超氧化物歧化酶(SOD)活力及谷胱甘肽过氧化物酶(GSH-Px)活力.结果 Morris水迷宫实验中,各染毒组小鼠逃避潜伏期[(57.98±2.78)、(62.35±3.18)、(85.57±5.10)s]均明显高于对照组[(21.74±1.36)s],差异有统计学意义(P<0.05),并有剂量-反应关系(R=0.8629,P<0.05).避暗穿梭实验中,各染毒组小鼠主动回避潜伏期[(5.56±0.29)、(6.08±0.22)、(8.32±0.38)s]高于对照组[(3.50±0.13)s],差异有统计学意义(P<0.05),并有剂量-反应关系(R=0.9579,P<0.05).中、高剂量染毒组血清中MDA含量[(24.76±1.76)、(31.10±4.57)nmol/ml]明显高于对照组[(16.38±6.26)nmol/ml],差异有统计学意义(P<0.05);各染毒组海马组织中MDA含量[(2.26±0.18)、(2.77±0.20)、(3.37±0.39)nmol/mg Pro]明显高于对照组[(1.93±0.39)nmol/mg Pro],差异有统计学意义(P<0.05);各染毒组小鼠血清和海马组织中SOD及GSH-Px活力均低于对照组,差异有统计学意义(P<0.05).结论 百草枯可诱导的发育中小鼠海马组织氧化损伤,并导致小鼠学习记忆能力减退.

Abstract：

Objective To explore the damages of paraquat to the learning and memory ability of developing mice and explore the possible mechanism involving oxidative stress.Methods Eighty healthy Kunming mice in aged 21 days were divided into 4 groups randomly:a control group (distilled water) and three paraquat treatment groups.The doses of paraquat were 0.89,2.67 and 8mg/kg body weight,respectively.Paraquat was administered orally in doses of 0.1 ml/10 g body weight,respectively,once a day and for 28 consecutive days.The Morris water maze test and the shuttling and avoid dark box test were used to detect the learning and memory abilities of mice.The levels of MDA and the activities of SOD and GSH-PX were detected according to the commercial kits manual using a microplate reader.Results Morris water maze test showed that the escape latency of mice after paraquat treatment (57.98 ±2.78,62.35 ±3.18,85.57 ±5.10) were significantly increase compared with the control (21.74±1.36),respectively (P<0.05).There were good dose-response relationship (R=0.8629,P<0.05).The shuttling and avoid dark box test showed that initiative avoidance latency of mice after paraquat treatment (5.56 ±0.29,6.08 ±0.22,8.32 ±0.38) were significantly increase compared with the control (3.50 ±0.13),respectively (P<0.05).There were good dose-response relationship (R=0.9579,P<0.05 ).The levels of MDA in serum of mice in paraquat treatment groups (2.67 and 8mg/kg) (24.76±1.76,31.10±4.57) and in hippocampus of mice in each paraquat treatment groups were significantly increase compared with the control (serum:16.38±6.26,hippocampus:1.93±0.39) (P<0.05,respectively).The activities of SOD in serum and hippocampus of mice in each paraquat treatment groups were significantly decrease compared with the control (serum:213.25±6.78,hippocampus:197.36±6.37) (P<0.05,respectively).The activities of GSH-PX in serum and hippocampus of mice in each paraquat treatment groups were significantly decrease compared with the control (serum:583.47±11.23,hippocampus:412.38±13.16) (P<0.05,respectively).Conclusion Paraquat can induce the oxidative damage in hippocampus,and then influence the learning and memory abilities of developing mice.     

铅暴露对发育期小鼠学习记忆能力影响

目的 探讨不同铅暴露水平对发育期小鼠学习记忆能力的影响及脑一氧化氮(NO)、总一氧化氮合酶(NO S)与小鼠学习记忆能力的关系.方法 采用自由饮水(含醋酸铅)的方式对刚断乳小鼠染毒,染毒剂量为0.3,1和3g/L,每组30只.开始染铅记为第0d,分别在第7,14,21d进行血铅、小鼠Morris水迷宫试验及小鼠脑铅浓度、脑NO含量和脑总NO S活性的测定.结果 与正常对照组比较,染毒组小鼠血铅和脑铅浓度增加(P<0.05);迷宫实验中,第21d,正常组及染铅0.3,1,3g/L组平均潜伏期分别为(33.8±7.8),(73.0±12.1),(85.9±12.7),(101.3±19.7)s,各铅暴露组与对照组之间差异有统计学意义(P<0.05);正常组,0.3,1,3g/L组脑NO含量分别为(10.27±4.28),(6.07±1.95),(5.63±2.03)和(3.74±1.89)μmol/(g.prot),各铅暴露组与对照组之间的差异有统计学意义(P<0.05);正常组,0.3,1,3g/L组脑总NO S活性分别为(6.22±2.42),(4.36±1.76),(2.84±1.42)和(3.25±1.76)U/(m g.prot),各铅暴露组与对照组之间差异有统计学意义(P<0.05);第21d,小鼠脑NO含量和脑总NO S与血铅、脑铅浓度及M orris水迷宫逃避潜伏期均呈负相关(r=-0.540,P=0.000;r=-0.520,P=0.000;r=0.755,P=0.000;r=0.709,P=0.000).结论 铅暴露对发育期小鼠学习记忆能力的影响与铅暴露导致的脑NO S活性降低和NO含量减少密切相关,且影响程度与铅的暴露时间及浓度有关.     

莱菔硫烷对阿尔茨海默病模型小鼠学习记忆和胆碱能系统的影响

目的探讨莱菔硫烷(SFN)对阿尔茨海默病(AD)模型小鼠学习记忆和胆碱能系统的影响,为防治AD提供理论依据。方法健康成年C57BL/6J小鼠按体重随机分为3组,每组18只,雌雄各半。模型组和干预组小鼠饮用含铝水(浓度为0.4 g/100 ml),并隔日皮下注射200 mg/kg D-半乳糖,此外,干预组小鼠每日1次灌胃给予25 mg/kg SFN,模型组小鼠每日1次灌胃等量蒸馏水,同时设立溶媒对照组。每日1次观察小鼠的一般状况,并每周称重1次,90 d后采用跳台实验测定小鼠的学习记忆能力,石墨炉原子吸收光谱法测定脑组织铝含量,乙酰胆碱转移酶(ChAT)免疫组化法观察海马CA1区胆碱能神经元丢失情况,分光光度计法测定大脑皮层乙酰胆碱(Ach)含量、乙酰胆碱酯酶(AChE)和ChAT活性,Real-time PCR法检测大脑皮层ChAT mRNA的表达。结果在整个受试期间各组小鼠均未见异常表现及死亡,各组小鼠体重差异无统计学意义(P0.05)。与对照组相比,模型组小鼠学习记忆能力下降(P0.01),脑铝含量增高(P0.01),海马CA1区胆碱能神经元细胞数减少(P0.05)。与模型组相比,SFN能提高小鼠的学习记忆能力(P0.01),降低脑铝含量(P0.01),增加海马CA1区胆碱能神经细胞数(P0.05)。此外,干预组小鼠脑铝含量高于对照组(P0.01),大脑皮层ChAT mRNA水平低于对照组和模型组(P0.05);各组小鼠大脑皮层Ach含量、AChE和ChAT活性差异无统计学意义(P0.05)。结论 SFN可明显减少AD模型小鼠胆碱能神经元的丢失,提高其学习记忆能力。     

纳米硒对小鼠学习记忆和含硒酶活性的影响

目的以传统硒源亚硒酸钠为对照,探究纳米硒(Nano-Se)对小鼠学习记忆、脑组织和肝组织中两种含硒酶活性的影响。方法用两种硒源的硒分别以每只1、2、4μgSe/d的水平对小鼠进行灌胃。运用Y型迷宫试验测试小鼠的学习记忆能力;测定各组小鼠脑组织、肝脏中的谷胱甘肽过氧化物酶(GSH-Px)和脱碘酶(ID)活性。结果纳米硒(Nano-Se)三个剂量组小鼠与对照组比较,学习记忆成绩均有明显改善(P<0.01或P<0.05),脑组织和肝脏中的GSH-Px和ID活性明显升高(P<0.01或P<0.05),且均强于同剂量的亚硒酸钠组(P<0.01或P<0.05)。结论纳米硒(Nano-Se)能提高小鼠的学习记忆能力及脑和肝脏两种含硒酶活性。     

宫内接触氯化甲基汞对发育阶段小鼠学习记忆能力和海马神经元超微结构的影响

目的　研究宫内接触氯化甲基汞对发育阶段小鼠学习记忆能力及海马神经元超微结构的影响.方法　对妊娠7～10天的小鼠每天灌胃给予0和4mg kgbw氯化甲基汞。以出生6周龄仔鼠进行学习记忆能力测试及透射电镜技术观察宫内接触氯化甲基汞对发育阶段小鼠学习记忆能力及海马神经元超微结构的影响。结果　氯化甲基汞暴露组学习记忆能力显著低于对照组(P <0 . 0 5 )。超微结构显示海马神经元细胞膜结构不清,部分核膜消失,核膜皱缩,核孔不清,染色质淡染;线粒体肿胀变大、粗面内质网扩张、空泡变性,核糖体减少;轴突环出现分层;有髓神经纤维脱髓鞘、板状分离。结论　甲基汞可致小鼠学习记忆障碍和海马神经元超微结构改变;宫内接触氯化甲基汞引起海马神经元超微结构的改变与小鼠学习记忆障碍密切相关。     

姜黄素对D-半乳糖所致痴呆模型小鼠空间学习记忆的影响

目的研究姜黄素(curcumin,Cur)对D-半乳糖所致痴呆模型小鼠空间学习记忆的影响。方法选用健康雄性ICR小鼠50只随机均分为正常对照组、模型组、预处理组、同时处理组、后处理组,各组分别灌胃相应药物45 d后,采用Morris水迷宫进行行为学测试,以乙酰胆碱酯酶(acetylcholine estera,AChE),胆碱乙酰转移酶(choline acetyltransterase,ChAT)为指标,观察其对痴呆小鼠学习记忆的影响。结果不同给药方式的姜黄素均能提高小鼠学习记忆成绩,小鼠脑组织中ChAT活力升高,AChE活力降低,但预处理组和同时处理组对痴呆小鼠学习记忆影响与后处理组差异有统计学意义(P0.05)。结论姜黄素对D-半乳糖所致痴呆小鼠的学习记忆能力下降有明显保护作用,其作用机制可能与抑制AchE活力作用密切相关。     

全氟辛烷磺酸亚慢性暴露对小鼠学习记忆及海马神经元的影响

目的 探讨全氟辛烷磺酸(perfluorooctane sulphonate,PFOs)暴露对小鼠的学习记忆能力及海马神经元的影响.方法 将32只健康清洁级8周龄雄性ICR小鼠按体重随机分为4组,分别为对照(含2％吐温-80的生理盐水)组和5、20、40 mg/kg PFOS暴露组,每组8只.采用腹腔注射方式进行染毒,染毒容量为10 ml/kg,每周3次,连续染毒6周.采用Morris水迷宫实验检测小鼠空间学习、记忆能力,并进行海马神经元形态学的定量分析.结果 训练第1天20 mg/kgPFOS暴露组小鼠的逃避潜伏期长于对照组(P＜0.05),而40 mg/kg PFOS暴露组小鼠训练第1、2天和第5天的逃避潜伏期均较对照组延长(P＜0.05,P＜0.01).与对照组相比,5、20 mg/kg PFOS暴露组小鼠海马CA1和CA3区神经元密度、细胞面积和核黑度差异无统计学意义(P＞0.05);而40 mg/kg PFOS暴露组小鼠海马CA1区神经元密度下降,胞面积减小,核黑度值增大,且CA3区神经元密度也下降,差异均有统计学意义(P＜0.01).结论 一定剂量的PFOS暴露可使小鼠学习记忆能力减弱,可能与海马区神经元损伤有关.     

Nardostachys jatamansi improves learning and memory in mice

Cure of cognitive disorders such as amnesia, attention deficit, and Alzheimer's disease is still far from being realized in the field of medicine. Nootropic agents such as piracetam, aniracetam, and choline esterase inhibitors like donepezil are being used for improving memory, mood, and behavior, but the resulting side effects associated with these agents have made their applicability limited. In Ayurveda, the roots of Nardostachys jatamansi have been clinically employed for their anti-ischemic, antioxidant, anticonvulsant, and neuroprotective activities. The present study was undertaken to assess the potential of N. jatmansi as a memory enhancer. The elevated plus maze and the passive avoidance paradigm were employed to evaluate learning and memory parameters. Three doses (50, 100, and 200 mg/kg, p.o.) of an ethanolic extract of N. jatamansi were administered for 8 successive days to both young and aged mice. The 200 mg/kg dose of N. jatmansi ethanolic extract significantly improved learning and memory in young mice and also reversed the amnesia induced by diazepam (1 mg/kg, i.p.) and scopolamine (0.4 mg/kg, i.p.). Furthermore, it also reversed aging-induced amnesia due to natural aging of mice. As scopolamine-induced amnesia was reversed, it is possible that the memory improvement may be because of facilitation of cholinergic transmission in the brain. Hence, N. jatmansi might prove to be a useful memory restorative agent in the treatment of dementia seen in elderly persons. The underlying mechanism of action can be attributed to its antioxidant property.     

妊娠压力与铅联合暴露对大鼠子代空间学习记忆的影响

目的 探讨妊娠压力与铅联合暴露对大鼠子代早期空间学习记忆能力的影响.方法 运用数字表法随机将32只Sprague-Dawley孕鼠分为空白对照组(NS/C),铅暴露组(NS/L),压力暴露组(S/C),联合暴露组(S/L),每组8只.NS/L、S/L自由饮用0.2%醋酸铅溶液,S/C、S/L给予束缚压力.子代于30 d龄进行Morris水迷宫测试,并检测海马组织铅含量及水迷宫实验前、后血清肾上腺酮.结果 S/L雄、雌性仔鼠在原平台所在象限停留时间分别为(16.08 ±3.41)s、(15.72 ±3.33)s,显著短于NS/L(25.42±4.76)s、(24.55±4.43)s和S/C(20.96±3.45)s、(20.65±2.98)s,妊娠压力与铅对仔鼠在原平台所在象限停留时间的影响存在交互作用(F=5.478,P<0.05);妊娠压力与铅对仔鼠应激后血清肾上腺酮水平的影响存在交互作用.NS/L、S/L仔鼠海马铅含量分别为(0.4378 ±0.1041)μg/g、(0.4679 ±0.1243)μg/g,差异无统计学意义(F=0.298,P0.05).结论 (1)妊娠压力与铅对大鼠子代学习记忆的损害可能具有叠加作用.(2)妊娠压力与铅对仔鼠下丘脑.垂体-肾上腺轴的影响可能具有叠加作用.该作用可能是二者对子代学习记忆叠加损害的原因之一.(3)联合暴露未显著增加铅在子代海马中的蓄积.     

维生素E和N-乙酰半胱氨酸对甲醛所致小鼠学习记忆能力改变的影响

目的探讨维生素E(VitE)和N-乙酰半胱氨酸(NAC)两种抗氧化剂对甲醛(FA)所致小鼠学习记忆能力损伤的保护作用。方法将34只清洁级ICR小鼠随机分为对照组(生理氯化钠,n=8)、FA组(15 mg/kg,n=9)、FA(15mg/kg) NAC(100 mg/kg)组(n=9)、FA(15 mg/kg) VitE(100 mg/kg)组(n=8)。每日给药1次,连续7 d。第8天开始用六臂放射状水迷宫检测小鼠的学习记忆能力,连续检测7 d。并检测谷胱甘肽(GSH)、丙二醛(MDA)。结果FA组小鼠早期兴奋后期则静卧少动,其余各组小鼠无此现象。体重增长在各组小鼠间比较,差异无统计学意义(P>0.05)。经重复测量资料方差分析,发现FA组小鼠学习期和记忆期潜伏时间延长,差异有统计学意义(F=5.479和2.953,P<0.01);但学习期和记忆期的小鼠错误次数差异无统计学意义(P>0.05);FA组的GSH含量高于对照组,差异有统计学意义(P<0.05)。两个干预组的MDA低于FA组,但差异无统计学意义(P>0.05)。结论抗氧化剂对FA致小鼠学习记忆能力损伤有保护作用。     

Effect of Monascus-fermented products on learning and memory in the SAMP8 mice

The purpose of this study was to evaluate the impact of Monascus-fermented products (MP) as regards certain changes in behavior for SAMP8 mice. Both male and female SAMP8 mice were fed a 0.03% MP diet from 3 mo of age to 11 mo of age. The results indicated that the grading score of passive avoidance behavior was significantly lower in the MP diet groups than in the control diet groups in both male and female SAMP8 mice (p < 0.05). The MP diet-augmented test-animal body weight, feed intake and feed efficiency did not differ significantly from the corresponding values for control mice. The MP diet-fed mouse group revealed significantly improved learning and memory as revealed by average escape-response testing score when comparing with control mice (p < 0.05). Further, the level of serum triglyceride and total cholesterol for the MP-fed group were shown to be significantly lower than for the control group of SAMP8 mice at 11 mo of age. The test mice fed an MP diet appeared to be significantly lower in aging score than the control group (p < 0.05). The MP diet-fed mouse group revealed significantly improved total antioxidation of liver. Subsequent to supplementation of SAMP8 mice diets with MP for a period of 8 mo, these MP-fed mice revealed significantly lower lipofuscin-cell numbers within the hippocampus (p < 0.05). The results suggest that dietary supplementation with MP might improve both learning and memory behaviour, and retard the aging process for SAMP8 mice.     

纳米氧化铝急性染毒对小鼠学习记忆能力的影响

目的 探讨不同粒径的纳米氧化铝(nano-Al2O3)急性染毒对小鼠学习记忆能力的影响.方法 选取90只健康成年ICR小鼠,每组18只,分为溶剂对照组(生理盐水)、13 nm Al2O3组、50 nm Al2O3组和10 μm Al2O3组.用灌胃法进行急性染毒,染毒剂量均为5 g/kg,染毒后观察期分别为3、7和14 d.第14天观察期结束后用Morris水迷宫对小鼠进行学习记忆能力检测.处死小鼠,取脑,测脑体比,分离皮质,检测炎症因子和氧化应激水平.结果 与溶剂对照组相比,各染毒组小鼠体重及脑体比差异均无统计学意义;水迷宫结果显示,13 nm Al2O3组与其余各组相比,学习记忆能力显著下降,差异有统计学意义(P＜0.05);炎症因子结果显示:与溶剂对照组相比,炎症因子[首先在第3天肿瘤坏死因子-α(TNF-α)、第7天白介素1-β(IL-1β)]显著升高,各组差异均有统计学意义(P＜0.05),且有随粒径减小含量显著增加的趋势(P＜0.05);但在第14天时,各组恢复到溶剂对照组水平.氧化应激结果显示,与溶剂对照组相比,各组的丙二醛(MDA)含量在第3天没有显著差异,从第7天开始显著增加,到第14天达到最高水平,差异有统计学意义(P＜0.05);且有随粒径减小含量显著增加的趋势(P＜0.05).与溶剂对照组相比,各组超氧化物歧化酶(SOD)活力从第3天开始随时间延长逐渐降低,到第14天观察期结束降到最低水平,差异有统计学意义(P＜0.05);且有随粒径减小其活力显著降低的趋势(P＜0.05).结论 纳米氧化铝可以降低小鼠的学习记忆能力,炎症因子是这一过程中的早期事件,而氧化应激水平的升高可能是学习记忆能力下降的主要原因之一.     

出生后早期接触速灭威对小鼠空间学习记忆能力的影响

目的观察出生后早期有限次数速灭威染毒对ICR小鼠青春期和成年早期神经行为和空间学习记忆能力的影响以及自主活动能力、感觉运动能力和焦虑情绪是否影响空间学习记忆能力,并探明其影响的发生时间。方法小鼠出生后随机分为5组,即速灭威高、中、低剂量组（5 mg/kg、0.5 mg/kg、0.05 mg/kg,）,溶剂对照组（DMSO）和生理盐水对照组（NS）,于出生后第3、5、7、9、11、13天进行腹腔注射染毒。观察一般生理发育情况,并选用成组的神经行为学实验在青春期（～PND60）和成年早期（～PND90）进行测试。结果青春期小鼠平衡木得分与染毒剂量呈负相关关系（rs=-0.418,P〈0.05）;青春期和成年早期的洞板实验和旷场实验中各指标在同期各组间均无统计学意义;青春期Morris水迷宫空间探索实验中,定位航行结束后和次日的两次穿越平台位置次数与染毒剂量之间均呈负相关关系（rs分别为-0.361和-0.277,P〈0.05）;成年早期Morris水迷宫空间探索实验中,第四象限时间百分比与染毒剂量之间呈负相关关系（rs=-0.390,P〈0.05）;主成分分析发现,反映空间学习记忆能力与自主活动能力、感觉运动能力及焦虑情绪的指标出现在不同的主成分中。结论出生后早期有限次数接触速灭威可能在青春期时已经开始影响到小鼠的空间记忆能力,这可能是成年后空间学习记忆能力损害的重要线索。     

水飞蓟宾对快速老化小鼠学习记忆影响

目的探讨水飞蓟宾对快速老化小鼠（SAMP8）学习记忆及氧化应激因子表达影响。方法以SAMP8小鼠为模型,采用新物体辨别、Y迷宫及Morris水迷宫进行学习记忆能力评价,酶联免疫实验检测氧化应激相关指标。结果与对照组比较,模型组小鼠优先指数（0.45±0.07）、自发交替反应率[（0.58±0.06）%]明显下降,逃避潜伏期[（50.62±11.24）s]明显延长（P<0.01）,小鼠海马组织中谷胱甘肽（GSH）、超氧化物歧化酶（SOD）水平[分别为（21.13±6.17）mg/mL、（15.21±0.09）μg/mL]降低,丙二醛含量[（4.02±0.12）nmol/mL]升高（P<0.05）;与模型组比较,水飞蓟宾200 mg/kg组小鼠优先指数（0.68±0.09）、自发交替反应率[（0.70±0.09）%]升高,逃避潜伏期[（23.45±11.94）s]明显缩短（P<0.01）,小鼠海马组织中GSH、SOD水平[分别为（42.37±12.08）mg/mL、（32.24±0.24）μg/mL]升高,丙二醛含量[（2.54±0.21）nmol/mL]明显降低（P<0.05）。结论水飞蓟宾可改善快速老化小鼠学习记忆障碍,其机制可能与提高小鼠抗氧化应激能力有关。     

三氯化铝对大鼠学习记忆的影响

目的　研究三氯化铝对学习记忆及脑神经细胞数和海马颗粒空泡变性 (GVD)的影响。方法　将 14 4只大鼠分为腹腔注射AlCl3 剂量组和生理盐水对照组 ,于染铝 4、 8、 12周时分别进行跳台实验 ,第二天处死动物 ,取各脑区标本进行光镜观察。结果　大鼠跳台实验表明 ,与对照组比较 ,各时间剂量组大鼠主动回避次数显著下降 ,被动逃避延迟时间显著延长 (P <0 0 1)。 15 0mg/kg 4周及 5 0mg/kg 12周组就有大脑顶叶锥体层锥体细胞、海马锥体细胞和小脑浦肯野细胞数显著减少 (P <0 0 1)。 5 0mg/kg 8周组、 15 0mg/kg及 2 5 0mg/kg 4周组的GVD细胞数显著增加(P <0 0 1) ,且各剂量组细胞GVD阳性率与铝剂量有显著相关性。结论　证实了铝对大鼠学习记忆的影响 ,提示该毒性与铝导致神经细胞数减少和海马GVD细胞增加有关     

Effects of age and dietary restriction on animal model SAMP8 mice with learning and memory impairments

This study was to investigate a hypothesis that dietary restriction (DR) suppresses learning and memory impairments in dementia animal model SAMP8 mice. Four-week-old female SAMP8 mice were fed either ad libitum (AL) or fed restricted (40% of the food consumed by AL). Results showed that acetylcholine (ACh) levels in hippocampus at aged 12 months of age were 12% higher in DR than that of AL group. Dopamine (DA) and norepinephrine (NE) levels in cerebellum at 8 and 12 months of age were significantly higher (26~94% and 34~43%, respectively) in DR group than those in AL group. Serotonin (5-HT) levels in cerebellum at aged 12 months of age were markedly increased (~53%) in DR group. Homovanillic acid (HVA) and 5-hydroxyindole acetic acid (5-HIAA) levels in cerebellum at 8 and 12 months of age were significantly increased (28~41% and 24~64%, respectively) in DR group compared with AL group. In addition, neurotransmitter-related enzymes, choline acetyltransferase (ChAT) and acetylchoinesterase (AChE) activities at 8 and 12 months of age were elevated (6~8% and 5~7%, respectively) in DR group. Monoamine oxidase-B (MAO-B) that catalyzes oxidative deamination in brain were suppressed by 7~10% in DR group. At aged 12 months of age, the generation of basal and induced reactive oxygen species (ROS) in brain significantly decreased by 20% in DR group compared with AL group. These results suggest that inhibitory effect of oxidative stress by DR may play a pivotal role in attenuating the age-related changes observed in dementia animal model SAMP8.     

牛磺酸对高碘仔鼠脑发育和学习能力的影响

目的：探讨牛磺酸对高碘仔鼠脑发育和智力的影响。方法：将动物随机分为3组：适碘组、高碘组、高碘＋0．6％牛磺酸组（简称牛磺酸组）,各组亲代小鼠饲养3个月后雌雄交配,测定各组30日龄仔鼠的学习记忆能力及脑组织相关生化指标。结果：高碘组30日龄仔鼠脑蛋白质和DNA含量下降,牛磺酸组与适碘组差异无显性：高碘组30日龄仔鼠脑海马组织乙酰胆碱酯酶活性比适碘组和牛磺酸组明显升高,乙酸胆碱含量下降。与适碘组相比,牛碘酸组乙酰胆碱酯酶活性无统计学差异,而乙酰胆碱含量上升。结论：牛磺酸能拮抗高碘所致的发育障碍。