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。     

两种水迷宫在测试拟阿尔茨海默病小鼠学习记忆能力中的比较

目的采用两种水迷宫对拟阿尔茨海默病小鼠学习记忆功能进行比较。方法将小鼠分为正常对照组、模型组及给药组。用Morris水迷宫和MS-2水迷宫自动控制仪分别测试各组小鼠的学习记忆能力。结果在Morris水迷宫测试中,模型组与对照组,给药组与模型组比较,逃避潜伏期均有显著性差异（P〈0.01）,在MS-2水迷宫自动控制仪测试中,模型组与对照组比较有明显差异（P〈0.05）,而给药组与模型组比较,游出水迷路的时间均有所减少,但没有显著性差异（P〉0.05）。结论Morris水迷宫和MS-2水迷宫自动控制仪测试方法均能反映动物学习和记忆功能,而前者能更敏感地反映出动物的学习记忆能力。因此,Morris水迷宫应为实验首选,当然在实验需要时,两种水迷宫最好结合使用,以得到客观的结果。     

三种老年痴呆动物模型行为学比较

目的老年大鼠、基底前脑损伤大鼠及注射东莨菪碱大鼠常作为老年性痴呆的动物模型,本研究对这三种模型的行为表现进行比较研究。方法采用水迷宫及旷场分析法对这三种模型及青年对照和假手术对照进行了研究。结果老年大鼠、基底前脑损伤大鼠和注射东莨菪碱大鼠的学习记忆能力显著减弱,老年大鼠对新环境的紧张程度增强;基底前脑损伤大鼠和注射东莨菪碱大鼠的空间认知能力显著下降;注射东莨菪碱大鼠的兴奋性异常增强,（Ｐ＜００５）。结论基底前脑损伤动物的行为表现最符合老年痴呆患者的早期临床症状。     

东莨菪碱慢性给药大鼠作为老龄相关记忆损害模型的探索

目的对东莨菪碱慢性给药大鼠能否作为老龄相关记忆损害模型进行探索。方法14只1月龄SD大鼠随机分为对照组和东莨菪碱模型组。东莨菪碱模型组大鼠皮下注射东莨菪碱2mg kg,2次日,正常对照组予等量生理盐水,连续21d。然后利用Morris水迷宫(MWM)参照记忆试验进行行为学测试;神经元的特殊染色及电子显微镜技术,观察大鼠海马CA1、CA3区锥体细胞数、超微结构的改变以及突触可塑性变化。结果东莨菪碱组大鼠隐匿平台搜索实验成绩有一定损害;两组大鼠空间探索次数差异无显著性(P>0.05)。两组间海马CA1、CA3区锥体细胞数差异无显著性(P>0.05)。两组大鼠锥体细胞胞体超微结构无差异,但两组大鼠CA1区神经元突触超微结构有轻微变化。结论东莨菪碱慢性给药对大鼠学习记忆能力有一定损害,但对长时记忆无明显影响;对海马神经元结构无明显损害,对神经元突触可塑性有轻微影响。此种动物模型可能不是理想的老年性痴呆或老年相关记忆损害模型。     

磁场作用对小鼠学习记忆的影响

目的 :探讨磁场作用对小鼠学习记忆能力的影响。方法 :应用水迷宫学习模型测定并对比 30分钟磁场处理组、1 5分钟磁场处理组和非磁场处理的正常对照组动物的空间学习记忆能力。结果 :水迷宫学习训练的实验表明 30分钟磁场处理组与正常对照组比较 ,动物到达水下平台的时间延长 ;游程增加 ;平均游速减慢 ,且均具有显著性差异 (p <0 .0 5)。 1 5分钟磁场处理组与正常对照组比较 ,动物到达水下平台的时间延长 ,且具有显著性差异 (p <0 .0 5) ;游程和平均速度与正常对照组相比无显著性差异 (p >0 .0 5)。结论 :磁场处理 30分钟或 1 5分钟损伤小鼠的空间学习记忆能力 ,且以 30分钟的磁场处理作用较强     

两品系大鼠在经典条件反射和操作式条件反射中的行为学表现

目的探讨SD、Wistar两种品系大鼠在经典条件反射和操作式条件反射中行为学表现差异,为研究脑的高级功能建立稳定的条件反射动物模型提供实验动物选择依据。方法选择8周龄的正常SD和Wistar大鼠,分别进行奖赏训练、单次操作训练、连续多次操作训练三种检测模式,研究SD、Wistar大鼠学习记忆能力。结果奖赏训练中,SD大鼠的鼻触次数显著性增多(vs.Wistar,P0.05);单次操作训练中,与SD大鼠比较,Wistar大鼠的总踏板次数(LPs)、比率(c LP/LP)显著升高(P0.05),总鼻触次数(NPs)于第5天差异有显著性,踏板潜伏期明显降低(P0.05),踏板速率则显著性的升高(P0.05)。连续多次操作训练中,Wistar大鼠鼻触次数显著性升高(P0.05),踏板次数、奖赏次数均增多,反应准确率也高于SD大鼠,但组间差异无显著性(P0.05)。结论经典条件反射阶段SD大鼠对饮水盒的探索能力强,表现出对奖赏物质较强的兴趣;而在奖赏操作条件反射阶段Wistar大鼠的表现优于SD大鼠。     

恒定磁场对小鼠空间记忆形成的影响

目的探讨不同照射时间的恒定磁场作用对小鼠空间记忆形成的影响。方法应用水迷宫学习模型测定并对比4小时恒定磁场照射组、3小时恒定磁场照射组、2小时恒定磁场照射组和无磁场照射的正常对照组动物的空间记忆能力。结果水迷宫学习训练的实验表明第一个训练日中,4小时磁场处理组动物与正常对照组比较,动物到达水下平台所需时间延长,且具有显著性差异(P<0.05);3小时磁场处理组与正常对照组比较,动物到达水下平台所需时间缩短,且具有显著性差异(P<0.05);第二个训练日中,2小时或3小时磁场处理组与正常对照组比较,动物到达水下平台所需时间延长,且均具有显著性差异(P<0.05)。第三、四、五连续3个训练日中,3组磁场处理组动物到达水下平台所需的时间与正常对照组相比较均不具有显著性差异(P>0.05)。结论一定时间的磁场处理对小鼠空间记忆的形成有促进或损伤作用,究竟是促进还是损伤有可能取决于一个作用“窗口”问题。     

香水莲花提取物对东莨菪碱诱导记忆障碍小鼠学习记忆能力的影响

探究香水莲花提取物(Nymphaea hybrid extract,NHE)对东莨菪碱诱导记忆障碍小鼠的学习记忆能力的影响。采用腹腔注射东莨菪碱建立记忆障碍模型,Morris水迷宫实验测定小鼠空间学习和记忆能力。水迷宫实验结束后,断头处死小鼠,进行生化指标的测定。结果表明,与模型组小鼠相比,NHE干预后,小鼠的逃避潜伏期明显缩短(P <0. 01),目标象限停留时间百分比和穿越平台次数增加(P <0. 05或P <0. 01),小鼠海马和皮质区的SOD和GSH-PX活力显著升高(P <0. 01或P <0. 05),MDA含量极显著降低(P <0. 01),ACh E活性显著降低(P <0. 01),ACh含量增加(P <0. 01或P <0. 05)。同时,免疫印迹结果表明,NHE能够改善东莨菪碱引起小鼠海马和皮质中ERK、CREB磷酸化水平和BDNF蛋白表达的减少。综上,香水莲花提取物可以提高东莨菪碱诱导的记忆障碍小鼠的学习记忆能力,具体机制涉及缓解大脑的氧化应激损伤,平衡胆碱能系统,激活ERK-CREB-BDNF信号通路。     

恒定磁场对小鼠空间记忆形成的影响

目的：探讨不同照射时间的恒定磁场作用对小鼠空间记忆形成的影响.方法：应用水迷宫学习模型测定并对比4小时恒定磁场照射组、3小时恒定磁场照射组、2小时恒定磁场照射组和无磁场照射的正常对照组动物的空间记忆能力.结果：水迷宫学习训练的实验表明：第一个训练日中,4小时磁场处理组动物与正常对照组比较,动物到达水下平台所需时间延长,且具有显著性差异（P〈0.05）;3小时磁场处理组与正常对照组比较,动物到达水下平台所需时间缩短,且具有显著性差异（P〈0.05）;第二个训练日中,2小时或3小时磁场处理组与正常对照组比较,动物到达水下平台所需时间延长,且均具有显著性差异（P〈0.05）.第三、四、五连续3个训练日中,3组磁场处理组动物到达水下平台所需的时间与正常对照组相比较均不具有显著性差异（P〉0.05）.结论：一定时间的磁场处理对小鼠空间记忆的形成有促进或损伤作用,究竟是促进还是损伤有可能取决于一个作用“窗口”问题.     

D-半乳糖合并Meynert基底核损毁对海马长时程增强和突触形态的影响

目的 :研究D 半乳糖合并Meynert基底核损毁Alzheimer病 (AD)大鼠模型海马突触可塑性的变化。方法 :通过0 .96 %D 半乳糖致亚急性损伤及鹅膏蕈氨酸损毁Meynert基底核建立AD动物模型 ,应用行为学测试、电生理学方法和电镜观察 ,研究AD模型大鼠海马突触形态结构和长时程增强现象 (long termpotentiation ,LTP)的变化。结果 :①AD模型大鼠在Morris水迷宫的学习记忆能力明显低于对照组 ;②AD大鼠海马CA1区突触的数密度、面密度明显减少 ;③AD模型大鼠海马齿状回产生的LTP较对照组明显降低。结论 :海马突触结构改变和功能可塑性的降低可能与AD大鼠的学习记忆能力下降有关     

Premarin improves memory, prevents scopolamine-induced amnesia and increases number of basal forebrain choline acetyltransferase positive cells in middle-aged surgically menopausal rats

Conjugated equine estrogen (CEE) is the most commonly prescribed estrogen therapy, and is the estrogen used in the Women's Health Initiative study. While in-vitro studies suggest that CEE is neuroprotective, no study has evaluated CEE's effects on a cognitive battery and brain immunohistochemistry in an animal model. The current experiment tested whether CEE impacted: I) spatial learning, reference memory, working memory and long-term retention, as well as ability to handle mnemonic delay and interference challenges; and, II) the cholinergic system, via pharmacological challenge during memory testing and ChAT-immunoreactive cell counts in the basal forebrain. Middle-aged ovariectomized (Ovx) rats received chronic cyclic injections of either Oil (vehicle), CEE-Low (10 μg), CEE-Medium (20 μg) or CEE-High (30 μg) treatment. Relative to the Oil group, all three CEE groups showed less overnight forgetting on the spatial reference memory task, and the CEE-High group had enhanced platform localization during the probe trial. All CEE groups exhibited enhanced learning on the spatial working memory task, and CEE dose-dependently protected against scopolamine-induced amnesia with every rat receiving the highest CEE dose maintaining zero errors after scopolamine challenge. CEE also increased number of ChAT-immunoreactive neurons in the vertical diagonal band of the basal forebrain. Neither the ability to remember after a delay nor interference, nor long-term retention, was influenced by the CEE regimen used in this study. These findings are similar to those reported previously for 17 β-estradiol, and suggest that CEE can provide cognitive benefits on spatial learning, reference and working memory, possibly through cholinergic mechanisms.     

Age-related alterations of Nestin-immunoreactive neurons in rat basal forebrain with aged memory deficit

Age-related and aged memory deficit changes in Nestin-immunoreactive (Nestin-IR) neurons were studied following recent evidence of distinct Nestin-IR neurons within adult rat basal forebrain. Morris water maze task assessed spatial learning capacity of 3- and 24-month rats (aged-impaired and aged-unimpaired groups). Nestin-IR neuron distributional and morphological features were investigated by immunohistochemistry and positive neuronal number calculation. Nestin-IR neuron number declined with aging, especially aged-impaired. Significant negative correlations existed between average escape latencies and Nestin-IR neuron number in medial septum-diagonal band of Broca (MS-DBB). Correlations of rostral portion [medial septum (MS) and vertical limb diagonal band (vDB)] were higher than caudal portion [horizontal limb diagonal band (hDB)]. Aged-impaired showed reduced complexity of Nestin-IR neuron dendrite arborization and dendritic length. Nestin-IR astrocyte-like cells appeared scattered among Nestin-IR neurons on some aged-impaired slices. In conclusion, aged-impaired rats showed worse cognitive spatial performance and less Nestin-IR neuronal number compared to aged-unimpaired. Nestin-IR neuronal loss and morphological changes are some pathological characteristics of rat aged basal forebrain and may be important in neurobiological mechanisms of brain aging and aged memory deficit.     

Age-related alterations of Nestin-immunoreactive neurons in rat basal forebrain with aged memory deficit

Age-related and aged memory deficit changes in Nestin-immunoreactive (Nestin-IR) neurons were studied following recent evidence of distinct Nestin-IR neurons within adult rat basal forebrain. Morris water maze task assessed spatial learning capacity of 3- and 24-month rats (aged-impaired and aged-unimpaired groups). Nestin-IR neuron distributional and morphological features were investigated by immunohistochemistry and positive neuronal number calculation. Nestin-IR neuron number declined with aging, especially aged-impaired. Significant negative correlations existed between average escape latencies and Nestin-IR neuron number in medial septum-diagonal band of Broca (MS-DBB). Correlations of rostral portion [medial septum (MS) and vertical limb diagonal band (vDB)] were higher than caudal portion [horizontal limb diagonal band (hDB)]. Aged-impaired showed reduced complexity of Nestin-IR neuron dendrite arborization and dendritic length. Nestin-IR astrocyte-like cells appeared scattered among Nestin-IR neurons on some aged-impaired slices. In conclusion, aged-impaired rats showed worse cognitive spatial performance and less Nestin-IR neuronal number compared to aged-unimpaired. Nestin-IR neuronal loss and morphological changes are some pathological characteristics of rat aged basal forebrain and may be important in neurobiological mechanisms of brain aging and aged memory deficit.     

多靶点抗AD bis-MEP-乙二酰胺杂合物ZLA抑制神经元型AChE活性及促智作用研究

目的:探究ZLA对神经元型AChE的抑制活性及其对中枢胆碱能神经功能障碍导致的学习记忆功能减退的改善作用。方法:通过体外实验观察ZLA对神经元型AChE活性的影响;通过ex vivo实验观察ZLA体内AChE抑制活性;利用Morris水迷宫行为学实验探讨ZLA对东莨菪碱诱发的小鼠学习记忆功能障碍的改善作用。结果:ZLA明显抑制人SH-SY5Y神经元细胞和小鼠海马神经元来源的AChE活性。另外,ZLA腹腔注射后以剂量依赖性方式抑制小鼠脑内AChE活性。Morris水迷宫实验结果显示,ZLA显著改善东莨菪碱引起的学习和记忆功能障碍。结论:ZLA能够抑制神经元型AChE活性并具有促智作用。     

Continuous estrone treatment impairs spatial memory and does not impact number of basal forebrain cholinergic neurons in the surgically menopausal middle-aged rat

CEE (conjugated equine estrogens) is the most widely prescribed estrogen-only menopausal hormone therapy in the United States, and is comprised of over 50% estrone (E1) sulfate. Following CEE administration, E1 is the principal circulating estrogen. However, the cognitive and neurobiological effects of E1 in a middle-aged rodent model have not yet been evaluated. We assessed cognitive effects of continuous E1 treatment in middle-aged surgically menopausal rats using a maze battery. We also quantified number of choline acetyltransferase-immunoreactive (ChAT-IR) neurons in distinct basal forebrain regions known in earlier studies in to be impacted by the most potent naturally-circulating estrogen in rodents and women, 17β-estradiol (17β-E2), as well as CEE. On the spatial working memory delayed-match-to-sample water maze, the highest E1 dose impaired memory performance during acquisition and after delay challenge. E1 did not impact ChAT-IR neuron number in the medial septum (MS) or horizontal/vertical diagonal bands. In a comparison study, 17β-E2 increased MS ChAT-IR neuron number. Findings indicate that E1 negatively impacts spatial working memory and memory retention, and does not increase ChAT-IR neuron number in basal forebrain, as does 17β-E2. Thus, data from prior studies suggest that 17β-E2 and CEE can enhance cognition and increase number of ChAT-IR basal forebrain neurons, while here we show that E1 does not induce these effects. Findings from preclinical basic science studies can inform the design of specific combinations of estrogens that could be beneficial to the brain and cognition. Accumulating data suggest that E1 is not likely to be among these key beneficial estrogens.     

四逆散对疲劳大鼠学习记忆及脑内GABA_B1 表达的影响

目的:探讨四逆散对疲劳大鼠学习记忆及脑内GABA_B1受体的影响。方法:应用游泳训练和睡眠剥夺方法复制疲劳动物模型,运用Y-迷宫检测各组大鼠的学习记忆能力,采用免疫组化方法检测大鼠脑内GABA_B1受体阳性反应物的变化。结果:模型组与正常组相比,大鼠Y-迷宫正确反应率明显下降,错误反应率明显升高,大鼠脑内GABA_B1的阳性反应物数目明显增多;中药治疗组与模型组相比,正确反应率明显升高,错误反应次数明显下降,脑内GABA_B1受体的阳性反应物数目明显减少。结论:四逆散对疲劳大鼠学习记忆能力的下降具有改善作用。     

Neurotensin Regulation of Endogenous Acetylcholine Release from Rat Cerebral Cortex: Effect of Quinolinic Acid Lesions of the Basal Forebrain

The effects of neurotensin (NT) on endogenous acetylcholine (ACh) release from basal forebrain, frontal cortex, and parietal cortex slices were tested. The results show that NT differentially regulates evoked ACh release from frontal and parietal cortex slices without altering either spontaneous or evoked ACh release from basal forebrain slices. In the frontal cortex, NT significantly inhibited evoked ACh release by a tetrodotoxin (TTX)-insensitive mechanism, suggesting an action directly on cholinergic terminals. In the parietal cortex, NT enhanced evoked ACh release by a TTX-sensitive mechanism, suggesting an action of NT on the cholinergic neuron or in close proximity to the cholinergic neuron. The effects of NT on ACh release were confined to evoked ACh release; that is, spontaneous ACh release was not affected. NT did not affect spontaneous or potassium-evoked ACh release from occipital cortex slices. The second set of experiments tested the effects of quinolinic acid (QUIN) lesions of the basal forebrain cell bodies on the NT-induced regulation of evoked ACh release in the cerebral cortex. QUIN lesions of basal forebrain cell bodies caused decreases in choline acetyltransferase activity (27 and 28%), spontaneous ACh release (14 and 21%), and evoked ACh release (38 and 44%) in frontal and parietal cortex, respectively. In addition, 11 days following QUIN lesions of basal forebrain cell bodies, the action of NT to regulate evoked ACh release in frontal cortex or parietal cortex was no longer observed. The results suggest that in the rat frontal and parietal cortex, NT differentially regulates the activity of cholinergic neurons by decreasing and increasing evoked ACh release, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

钩藤散浸膏对小鼠记忆障碍模型的影响

目的观察钩藤散浸膏的益智作用。方法小鼠随机均分为6组,3个实验组每天灌胃高、中、低剂量的钩藤散浸膏,模型对照组与正常对照组每天灌胃蒸馏水(0.2 mL/10 g),阳性对照组每天给与茴拉西坦溶液(三乐喜,0.2 g生药/kg.bw),连续给药3周后,除正常对照组外,用东莨菪碱、亚硝酸钠、40%乙醇分别复制小鼠记忆获得障碍、记忆巩固障碍、记忆再现障碍模型,用Y型迷宫法测定小鼠训练和测试成绩。结果三种模型实验组的训练、测试成绩都显著好于模型对照组(P<0.01),记忆再现障碍模型的实验组测试成绩明显高于正常对照组(P<0.01)。结论钩藤散浸膏对各模型小鼠的记忆障碍皆有明显的改善作用,说明钩藤散浸膏有一定的益智作用。     

四逆散对疲劳大鼠学习记忆及脑内GABA_B1表达的影响

目的：探讨四逆散对疲劳大鼠学习记忆及脑内GABA_B1受体的影响。方法：应用游泳训练和睡眠剥夺方法复制疲劳动物模型,运用Y-迷宫检测各组大鼠的学习记忆能力,采用免疫组化方法检测大鼠脑内GABA_B1受体阳性反应物的变化。结果：模型组与正常组相比,大鼠Y-迷宫正确反应率明显下降,错误反应率明显升高,大鼠脑内GABA_B1的阳性反应物数目明显增多;中药治疗组与模型组相比,正确反应率明显升高,错误反应次数明显下降,脑内GABA_B1受体的阳性反应物数目明显减少。结论：四逆散对疲劳大鼠学习记忆能力的下降具有改善作用。