叠氮钠对模型大鼠学习记忆能力的影响

目的 观察叠氯钠对模型大鼠学习记忆能力及脑内胆碱乙酰基转移酶（ChAT）活性的影响,探讨线粒体缺陷损伤学习记忆功能的可能机制。方法 SD大鼠皮下埋植Alzet微泵,连续恒速给予叠氮钠共28d,给药1mg/kg&;#183;h和2mg/kg&;#183;h两个剂量组。Morris水迷宫、通道式水宫检测动物学习记忆能力。放射化学分区测定脑皮层和海马ChAT活性。结果 大鼠水迷宫游出时间及距离延长、错误次数增加。大鼠皮和海马ChAT活性降低。结论 Cox活性下降可以导致动物学习记忆能力及脑内ChAT活性下降,使乙酰胆碱Ach代谢的障碍,可能是模型大鼠学习记忆能力下降的机制之一。     

葛根素对慢性低O2高CO2大鼠学习记忆的影响

目的:探讨不同剂量葛根素对低O2高CO2大鼠学习记忆能力和脑内胆碱乙酰转移酶(cholineacetyl-transferase,ChAT)活性的影响。方法:建立慢性低O2高CO2大鼠模型,并给予大(50mg/kg)、小(25mg/kg)剂量葛根素干预。用Morris水迷宫检测学习记忆能力,用放射化学法测定大鼠皮层、海马ChAT活性。结果:慢性低O2高CO2处理后,与对照组相比,模型组大鼠平均潜伏期明显延长(P<0.01),各脑区ChAT活性均显著降低(P<0.01)。药物干预后,与模型组相比,大、小剂量组大鼠平均潜伏期缩短(P<0.05),各脑区ChAT活性均显著升高(P<0.05),而大小剂量组间差异无显著性(P>0.05)。结论:葛根素可改善慢性低O2高CO2大鼠学习记忆能力并提高其脑内ChAT活性。     

重复经颅磁刺激对血管性痴呆大鼠学习记忆功能及海马胆碱能系统的影响

目的:观察重复经颅磁刺激(rTMS)对血管性痴呆(VaD)大鼠学习记忆功能及海马胆碱能系统的影响,并探讨其可能的作用机制。方法:雄性SD大鼠54只,随机分为对照组、模型组、rTMS组,每组18只。采用两血管阻断法制作VaD模型,对照组仅分离暴露双侧颈总动脉而不结扎。rTMS组于制模成功后给予rTMS治疗,模型组模拟rTMS固定大鼠头部放置线圈但不给予脉冲磁刺激。各组在造模第30天应用Morris水迷宫试验检测学习记忆能力,测定海马内乙酰胆碱酯酶(AChE)及胆碱乙酰转移酶(ChAT)的活性,行海马CA1区胆碱酯酶阳性纤维染色及密度测定,应用免疫组化技术检测海马CA1区脑源性神经营养因子(BDNF)的表达。结果:与模型组相比,rTMS组水迷宫逃避潜伏期明显缩短(P<0.05),相同时间内在原平台象限跨越相应平台次数明显增多(P<0.05);与对照组相比,模型组及rTMS组AChE及ChAT的活性均明显降低(P<0.05);与模型组相比,rTMS组AChE及ChAT的活性均明显增加(P<0.05);rTMS组海马CA1区乙酰胆碱酯酶阳性纤维的密度及BDNF的表达均较模型组明显增强(P<0.05)。结论:rTMS能改善VaD大鼠学习记忆功能,机制可能与rTMS治疗能促进海马CA1区BDNF的表达、恢复海马胆碱能系统活性有关。     

肉苁蓉多糖对阿尔茨海默病大鼠学习记忆及脑组织胆碱能系统的影响

目的:探讨肉苁蓉多糖(CDPS)对阿尔茨海默病(AD)大鼠学习记忆能力及脑组织胆碱能系统的影响。方法:60只大鼠随机分为正常对照组、假手术组、模型组、CDPS低剂量组、CDPS中剂量组和CDPS高剂量组,每组10只,后4组采用Aβ1-40侧脑室注射制备AD大鼠模型,CDPS低剂量组、CDPS中剂量组和CDPS高剂量组在制模后分别每天以50、100、200 mg/kg CDPS灌胃,正常对照组及模型组以等量玉米油灌胃,假手术组以等量生理盐水灌胃,均灌胃28 d,进行Morris水迷宫检测,比色法测定皮质及海马乙酰胆碱酯酶(AChE)和乙酰胆碱转移酶(ChAT)。结果:CDPS可缩短AD大鼠在Morris水迷宫的潜伏期,增加大脑皮质及海马AChE的含量,提高皮质中ChAT的活性。结论:CDPS可改善AD大鼠的学习记忆能力,其机制可能与对胆碱能系统的影响有关。     

智脑胶囊对阿尔茨海默病模型大鼠学习记忆及脑胆碱能神经递质系统的作用研究

背景尽管有许多研究涉及对实验性阿尔茨海默病( Alzheimer disease,AD)模型动物的药物干预研究,但基于既有动物行为学改变,又有典型神经病理学特征和神经生化学改变的理想的 AD动物模型所做的中药药效学研究仍属空白. 目的观察复方中药智脑胶囊对理想的实验性 AD模型大鼠学习记忆及大脑皮质和海马胆碱能神经递质的影响. 设计随机对照实验研究. 地点和材料本实验在中国科学技术大学生命科学学院及首都医学大学宣武医院神经物学实验室和安徽中医学院第一附属医院实验中心(国家中医药管理局三级实验室)完成.实验动物为清洁无菌级 Wistar大鼠,雄性,体质量 250～ 300 g ,购于安徽省医学研究所医学实验动物中心.随机分为正常组、模型组、对照组(模型+脑复康)和智脑Ⅰ 组(模型+智脑胶囊Ⅰ组)智脑Ⅱ组共 5组. 干预参加本实验的研究人员在国外文献基础上进行改进,采用β淀粉样蛋白大鼠侧脑室注射并联用转移生长因子β 1脑内注射制作出既有大鼠行为学改变(学习记忆障碍),又有典型病理学(β-淀粉样蛋白沉积斑)和神经生化学特征的实验性 AD大鼠模型,据此开展中药复方智脑胶囊对该模型大鼠学习记忆及大脑皮质和海马结构区胆碱能神经递质影响的药效学研究,在造模成功后 (通过行为学测试及病理学观察证实 ),开始给药.智脑胶囊两组分别给予大鼠智脑胶囊水溶液 2.0 g/( kg· d)、 4.0 g/( kg· d)灌胃,正常组、模型组均给予等容积的生理盐水灌胃;而对照组灌胃脑复康混悬液 100 mg/(kg· d),连续 28 d.应用水迷路法和避暗法测定实验性 AD模型大鼠空间辨别学习记忆能力(平均潜伏期)和被动回避反应(明室停留率),放射免疫法测定其大脑皮质和海马结构区乙酰胆碱( acetylcholine,Ach)含量、胆碱乙酰化酶( choline acetyltransferase,ChAT)和乙酰胆碱酯酶(acetylcholinesterase,AchE)活性. 主要观察指标①智脑胶囊对实验性 AD模型鼠学习记忆和被动回避的影响.②智脑胶囊对实验性 AD模型大鼠大脑皮质和海马 ChAT,AchE活性及乙酰胆碱含量的影响. 结果实验性 AD模型大鼠随天数后延,水迷路平均潜伏期明显增加,明室停留率显著下降 (28.7% ),模型大鼠大脑皮质和海马结构区乙酰胆碱含量降低 [(8.31± 2.14) nmol/g],ChAT活性下降 [(3.54± 0.42) nkat/L],AchE活性升高 [(0.21± 0.07) nkat/L],与对照组比较,差异有显著性意义( t=3.07～ 3.36,P均 < 0.01).智脑胶囊能缩短实验性 AD模型大鼠水迷路平均潜伏期,增加明室停留率,提高模型大鼠大脑皮质和海马结构区乙酰胆碱含量和 ChAT活性,降低 AchE活性,与模型组或脑复康对照组比较,差异有显著性意义( t=2.15～ 3.34,P< 0.05～ 0.01). 结论智脑胶囊可通过调节脑内胆碱能神经递质明显改善实验性 AD模型大鼠学习记忆能力.     

微泵恒速灌注叠氮钠致痴呆大鼠脑内胆碱及单胺类神经递质含量改变

目的 观察线粒体呼吸链复合体IV(线粒体细胞色素C氧化酶)抑制剂叠氮钠对大鼠脑内胆碱及单胺类神经递质的影响，探讨线粒体缺陷导致学习记忆障碍的可能机制。方法 SD大鼠皮下埋植Alzet微泵，连续恒速给予叠氮钠共30天，分为1mg／kg／h和2mg／kg／h两个剂量组。取脑，分区测定皮层和海马胆碱乙酰基转移酶(放射化学法)及乙酰胆碱酯酶(羟胺比色法)的活性，高效液相色谱法测定纹状体内单胺类神经递质及其代谢产物含量。结果 模型大鼠皮层和海马胆碱乙酰基转移酶活性降低，海马区乙酰胆碱酯酶活性升高，皮层和海马胆碱乙酰基转移酶与乙酰胆碱酯酶活性的比值明显降低。纹状体内单胺类神经递质及其代谢产物含量各组间无明显差异。结论 线粒体细胞色素C氧化酶活性的抑制可以导致动物脑内胆碱乙酰基转移酶及乙酰胆碱酯酶活性的异常，是模型大鼠学习记忆能力障碍的基础。微泵恒速灌注叠氮钠仅损伤大鼠脑内胆碱能神经系统，对脑内单胺类神经递质无影响，可作为拟痴呆模型，应用于发病机理及药理学等方面的研究。     

丰富环境对颅脑外伤大鼠学习记忆及海马神经元凋亡的影响

目的:研究丰富环境对颅脑外伤大鼠学习记忆能力及海马神经元凋亡的影响。方法:32只SD大鼠采用自由落体法建立颅脑外伤模型,排除差异后纳入研究,分为丰富环境组和对照组。在造模后11天开始进行连续4天水迷宫检测大鼠学习记忆能力,之后取脑观察海马区神经元形态及使用TUNEL法检测海马区神经元凋亡水平。结果:在水迷宫检测第4天丰富环境组大鼠学习记忆能力较对照组大鼠明显改善,差异有显著性意义(P0.05)。形态学检测发现丰富环境组大鼠海马区神经元凋亡水平较对照组明显减少,差异有显著性意义(P0.05)。结论:丰富环境可明显改善颅脑外伤大鼠学习记忆能力,其机制可能与减少海马区神经元凋亡,提高神经元存活水平相关。     

智脑胶囊对阿尔茨海默病模型大鼠学习记忆及脑胆碱能神经递质系统的作用研究

背景：尽管有许多研究涉及对实验性阿尔茨海默病(Alzheimer disease，AD)模型动物的药物干预研究，但基于既有动物行为学改变，又有典型神经病理学特征和神经生化学改变的理想的AD动物模型所做的中药药效学研究仍属空白。目的：观察复方中药智脑胶囊对理想的实验性AD模型大鼠学习记忆及大脑皮质和海马胆碱能神经递质的影响。设计：随机对照实验研究。地点和材料：本实验在中国科学技术大学生命科学学院及首都医学大学宣武医院神经物学实验室和安徽中医学院第一附属医院实验中心(国家中医药管理局三级实验室)完成。实验动物为清洁无菌级Wistar大鼠，雄性，体质量250～300g，购于安徽省医学研究所医学实验动物中心。随机分为正常组、模型组、对照组(模型十脑复康)和智脑Ⅰ组(模型+智脑胶囊Ⅰ组)智脑Ⅱ组共5组。干预：参加本实验的研究人员在国外文献基础上进行改进，采用13淀粉样蛋白大鼠侧脑室注射并联用转移生长因子β1脑内注射制作出既有大鼠行为学改变(学习记忆障碍)，又有典型病理学(β-淀粉样蛋白沉积斑)和神经生化学特征的实验性AD大鼠模型，据此开展中药复方智脑胶囊对该模型大鼠学习记忆及大脑皮质和海马结构区胆碱能神经递质影响的药效学研究，在造模成功后(通过行为学测试及病理学观察证实)，开始给药。智脑胶囊两组分别给予大鼠智脑胶囊水溶液2．0g／(kg&;#183;d)、4．0g／(kg&;#183;d)灌胃，正常组、模型组均给予等容积的生理盐水灌胃；而对照组灌胃脑复康混悬液100mg／(kg&;#183;d)，连续28d。应用水迷路法和避暗法测定实验性AD模型大鼠空间辨别学习记忆能力(平均潜伏期)和被动回避反应(明室停留率)，放射免疫法测定其大脑皮质和海马结构区乙酰胆碱(acetylcholine，Ach)含量、胆碱乙酰化酶(choline acetyltransferase，CHAT)和乙酰胆碱酯酶(acetylcholinesterase，AchE)活性。主要观察指标：①智脑胶囊对实验性AD模型鼠学习记忆和被动回避的影响。②智脑胶囊对实验性AD模型大鼠大脑皮质和海马ChAT，AchE活性及乙酰胆碱含量的影响。结果：实验性AD模型大鼠随天数后延，水迷路平均潜伏期明显增加，明室停留率显著下降(28．7％)，模型大鼠大脑皮质和海马结构区乙酰胆碱含量降低[(8．31&;#177;2．14)nmol／g]，ChAT活性下降[(3．54&;#177;0．42)nkat／L]，AchE活性升高[(0．21&;#177;0．07)nkat／L]，与对照组比较，差异有显著性意义(t=3．07～3．36，P均&;lt;0．01)。智脑胶囊能缩短实验性AD模型大鼠水迷路平均潜伏期，增加明室停留率，提高模型大鼠大脑皮质和海马结构区乙酰胆碱含量和ChAT活性，降低AchE活性，与模型组或脑复康对照组比较，差异有显著性意义(t=2．15～3．34，P&;lt;0．05～0．01)。结论：智脑胶囊可通过调节脑内胆碱能神经递质明显改善实验性AD模型大鼠学习记忆能力。     

参乌胶囊对拟杭廷顿病模型大鼠学习记忆能力的干预作用

背景参乌胶囊是由首都医科大学宣武医院药理研究室自行研制用于治疗老年痴呆的纯中药制剂,对多种拟痴呆模型动物的学习记忆能力有很好的改善作用. 目的观察拟杭廷顿病( Huntington disease,HD)模型大鼠学习记忆能力改变及参乌胶囊对其的干预作用,探讨其可能的作用机制. 设计随机对照的实验研究. 地点和材料实验地点 首都医科大学宣武医院药物研究中心.雄性 SD大鼠 60只,随机分为正常对照组 ,3-硝基丙酸( 3-nitropropionic acid , 3-NPA)模型组 ,参乌胶囊小剂量、中剂量和大剂量组,氟哌啶醇组.每组 10只.在实验进行中,正常对照组死亡 1只, 3-NPA模型组和参乌胶囊小剂量组各死亡 2只,氟哌啶醇组死亡 3只,考虑死亡原因为吸入性窒息. 干预 3-NPA模型组用 3-NPA 20 mg/kg对 SD大鼠隔日腹腔注射 1次,共 20 d,建立拟 HD大鼠模型.造模的同时,参乌胶囊小剂量 (0.45 g/kg)组,中剂量 (0.9 g/kg)和大剂量 (1.8 g/kg)组大鼠给予参乌胶囊连续灌胃 25 d.氟哌啶醇组自造模当日起给予氟哌啶醇,起始剂量为 100 μ g/( kg· d),隔日递增 ,直至 1 000 μ g/( kg· d). 主要观察指标大鼠在 Morris水迷宫中的游出时间和距离;在避暗实验中的潜伏期和错误次数;海马处胆碱乙酰基转移酶活性;大鼠海马 CA4区胶质细胞源性神经生长因子的细胞数量及细胞面积. 结果 Morris水迷宫实验中, HD模型大鼠游出时间和距离明显延长,参乌胶囊小和中剂量组较 3-NPA模型组游出时间分别缩短 24.01%和 32.64%,游出距离显著缩短.避暗实验中, 3-NPA模型大鼠较正常对照组动物进入暗箱的潜伏期显著缩短,参乌胶囊中、大剂量组较 3-NPA模型组动物进入暗箱的潜伏期明显延长.海马处, 3-NPA模型组大鼠较正常对照组 ChAT活性明显降低,参乌胶囊大剂量组和氟哌啶醇组较 3-NPA模型组动物 ChAT活性显著性增高( P< 0.01〉.海马 CA4区, 3-NPA模型组动物 GDNF阳性细胞的表达减少,阳性细胞总面积减少.而参乌胶囊中剂量组对于此区 GDNF阳性细胞的表达明显具增强作用. 结论拟杭廷顿病模型大鼠存在明显的学习记忆障碍,参乌胶囊可明显改善模型动物的学习记忆能力.     

低剂量索曼对大鼠空间记忆及脑乙酰胆碱酯酶活力的影响

目的研究慢性低剂量索曼(soman)染毒对大鼠空间学习记忆及脑组织胆碱酯酶(AChE)活力的影响,初步探讨慢性低剂量神经毒剂中毒的神经机制,为生化战争、武器消减意外事故和恐怖袭击情况下低剂量索曼中毒的临床预防和治疗提供理论依据。方法以皮下注射索曼(2～40μg/kg,s.c,sig×14)为大鼠染毒模型,采用Morris水迷宫试验进行行为检测,比色法测脑组织AChE活力。结果Morris水迷宫试验中,10μg/kg组和40μg/kg组大鼠逃避潜伏期分别为(9.1±2.1)s和(15.6±3.1)s,明显长于对照组(3.3±0.5)s(F=30.042,P<0.05);撤除平台后跨越原平台位置次数分别为(6.0±1.58)和(5.0±1.41),与对照组(11.2±1.5)相比明显减少;在原平台象限游泳时间百分比分别为(37.8±3.1)%和(34.0±2.6)%,明显低于对照组(52.6±3.6)%(P<0.01)。索曼组大鼠海马和前额叶皮质胆碱酯酶活力均明显低于对照组(F=107.054,51.858,P<0.01),且胆碱酯酶活力的降低呈剂量依赖性。10μg/kg组和40μg/kg组大鼠海马和前额叶皮质AChE活力抑制率均达30%以上。结论2μg/(kg·d)小剂量索曼慢性染毒对大鼠空间学习记忆能力无显著影响;10μg/(kg·d)和40μg/(kg·d)低剂量慢性索曼染毒降低大鼠空间学习记忆能力,这可能与乙酰胆碱过度堆积引起神经中枢胆碱能系统功能紊乱     

Effects of a novel cognitive enhancer, spiro[imidazo-[1,2-a]pyridine-3,2-indan]-2(3H)-one (ZSET1446), on learning impairments induced by amyloid-beta1-40 in the rat

We have previously shown that intracerebroventricular (i.c.v.) infusion of amyloid-beta (Abeta)1-40 produces oxidative stress and cholinergic dysfunction, as well as learning and memory deficits, in rats. In the present study, effects of a newly synthesized azaindolizinone derivative, spiro[imidazo[1,2-a]pyridine-3,2-indan]-2(3H)-one (ZSET1446), were assessed in rats with learning deficits induced by Abeta1-40 or scopolamine. The i.c.v. infusion of Abeta1-40 caused impairments in spontaneous alternation behavior in a Y-maze task, spatial reference and short-term memory in a water-maze task, and retention of passive-avoidance learning. Abeta1-40-infused rats also showed reduction in choline acetyltransferase (ChAT) activity in the medial septum and hippocampus, but not in the basal forebrain and cortex, and a decrease in glutathione S-transferase (GST)-like immunoreactivity in the cortex. Nicotine-stimulated acetylcholine (ACh) release in Abeta1-40-infused rats was lower than that in vehicle-infused rats. Oral administration of ZSET1446 at the dose range of 0.01 to 1 mg/kg ameliorated Abeta1-40-induced learning impairment in Y-maze, water-maze, and passive-avoidance tasks. ZSET1446 reversed the decrease of ChAT activity in the medial septum and hippocampus, GST-like immunoreactivity in the cortex, and nicotine-stimulated ACh release of Abeta1-40-treated rats to the levels of vehicle-infused control rats. Furthermore, 0.001 to 0.1 mg/kg ZSET1446 showed ameliorative effects on learning impairments caused by scopolamine in a passive-avoidance task. These results suggest that ZSET1446 may be a potential candidate for development as a therapeutic agent to manage cognitive impairment associated with conditions such as Alzheimer's disease.     

盐酸多奈哌齐对低灌注大鼠中枢胆碱能系统的影响

目的 观察盐酸多奈哌齐对于慢性低灌注大鼠额叶皮质及海马区胆碱酯酶浓度和胆碱酯酶阳性纤维密度的影响，并探讨其意义。方法 雄性SD大鼠112只，分为正常组、模型组、盐水治疗组和盐酸多奈哌齐治疗组。后3组均行双侧颈总动脉结扎，盐酸多奈哌齐治疗组大鼠术后采用盐酸多奈哌齐灌胃，剂量为每日3mg／kg体重；盐水治疗组采用相同剂量的生理盐水灌胃，连续治疗6周后进行水迷宫实验，并测定各组大鼠的胆碱酯酶水平及胆碱酯酶阳性纤维密度。结果 模型组大鼠与正常组大鼠相比，水迷宫完成时间显著延长，错误次数显著增多，胆碱酯酶浓度及胆碱酯酶阳性纤维密度也显著下降：盐酸多奈哌齐治疗组大鼠胆碱酯酶浓度及胆碱酯酶阳性纤维密度较模型组进一步下降，但水迷宫试验结果却较模型组大鼠有显著改善。结论 慢性低灌注能显著影响大鼠的认知功能，其原因可能与低灌注大鼠胆碱能系统受损有关；盐酸多奈哌齐对慢性低灌注所造成的认知功能损害有一定的防治作用，这一作用可能与其抑制胆碱酯酶，从而使脑组织中乙酰胆碱浓度升高有关。     

Behavioral and neurochemical changes in rats dosed repeatedly with diisopropylfluorophosphate

Behavioral effects of organophosphates (OPs) typically decrease with repeated exposure, despite persistence of OP-induced inhibition of acetylcholinesterase (AChE) and downregulation of muscarinic acetylcholine (ACh) receptors. To characterize this tolerance phenomenon, rats were trained to perform an appetitive operant task which allowed daily quantification of working memory (accuracy of delayed matching-to-position), reference memory (accuracy of visual discrimination) and motor function (choice response latencies and inter-response times during delay). Daily s.c. injections of 0.2 mg/kg of diisopropylfluorophosphate (DFP) caused no visible cholinergic signs, did not affect body weight or visual discrimination, but progressively impaired matching accuracy and lengthened response latencies and interresponse times. These effects recovered in seven of eight treated rats after termination of DFP treatment. Resumption of daily DFP at 0.1 mg/kg caused smaller impairments of both matching accuracy and response latency. After 21 injections of 0.2 mg/kg/day of DFP, rats were subsensitive to the hypothermia induced by acute oxotremorine (0.2 mg/kg i.p.), as expected after OP-induced downregulation of muscarinic ACh receptors. Evidence for supersensitivity to scopolamine (0.03 and 0.056 mg/kg i.p.) in DFP-treated rats was mixed, with additive effects predominating on both the cognitive and motor aspects of the task. After 18 days of 0.1 mg/kg of DFP, AChE was inhibited 50 to 75% and muscarinic ACh receptor density was reduced 15 to 20% in hippocampus and frontal cortex. Progressive declines in AChE activity in hippocampus and frontal cortex across 15 daily doses with DFP at 0.1 and 0.2 mg/kg were observed in other rats; quinuclidinyl benzilate binding was significantly reduced in hippocampus after 15 doses at both levels of DFP. These results indicate that animals showing a definitive sign of tolerance to OP administration (subsensitivity to a cholinergic agonist) were also functionally impaired on both the mnemonic and motoric demands of a working memory task. The nature of this impairment suggests further that it results from compensatory changes in the central nervous system, e.g., muscarinic receptor downregulation, considered to produce "tolerance" to OPs in exposed animals.     

Effects of prenatal nicotine exposure on development of central and peripheral cholinergic neurotransmitter systems. Evidence for cholinergic trophic influences in developing brain

The development of cholinergic systems in brain regions was evaluated biochemically in developing control rats and rats whose mothers received nicotine via continuous minipump infusion during gestational days 4 to 20. The cerebral cortex displayed a unique maturational pattern of choline acetyltransferase (ChAT) activity and high-affinity synaptosomal [3H]choline uptake capabilities, characterized by increases in the concentration of these components and a postnatal spike of neuronal activity as assessed with the uptake/ChAT ratio; the peak of activity coincided with the time at which neurogenesis declines and synaptogenesis rises. Evaluation of the same markers in midbrain + brainstem indicated rises in uptake which were relatively unselective, primarily reflecting tissue growth and no postnatal peak of uptake/ChAT; cerebellum likewise showed primarily tissue growth-related changes in ChAT rather than increases in its specific concentration. Prenatal exposure to nicotine had a marked adverse effect on developmental patterns of ChAT, uptake and uptake/ChAT only in cerebral cortex, the region previously shown to exhibit major abnormalities caused by this drug and other treatments with cholinomimetic effects. ChAT was unaffected in peripheral projections to the adrenal. Nicotine may thus selectively disrupt central nervous system development by stimulating nicotinic receptors which are present in fetal brain, prematurely eliciting the events ordinarily triggered postnatally by cholinergic projections.     

游泳训练对大鼠空间学习记忆能力与海马、前额叶皮质环磷酸腺苷、环磷酸鸟苷水平的影响

目的：探讨8周游泳训练对大鼠空间学习记忆能力的影响与环磷酸腺苷（cAMP）、环磷酸鸟苷（cGMP）信号传导途径的关系。方法：以大鼠为实验对象,采用Morris水迷宫法,研究8周游泳训练对大鼠空间学习记忆能力的作用;采用放射免疫法测定研究8周游泳训练对大鼠海马、前额叶皮质中cGMP、cAMP含量的影响。结果：①Morris水迷宫的测试表明,8周游泳训练后,大鼠的空间记忆能力有一定提高。②与安静组相比,8周游泳训练使大鼠海马cAMP水平非常显著性增加（P<0.01）,cAMP/cGMP比值显著性增高（P<0.05）,同时,前额叶皮质cAMP与cAMP/cGMP比值显著性增高（P<0.05）。结论：8周的游泳训练在提高大鼠空间学习记忆能力的同时伴有海马、前额叶皮质cAMP含量与cAMP/cGMP比值的变化,从而部分揭示了运动促进学习记忆能力提高的可能机制。     

血管性痴呆的动物模型、神经病理及其胆碱能机制

目的建立血管性痴呆(VD)的动物模型,并探讨VD认知障碍的发病机制。方法建立老龄大鼠VD模型,进行数字减影血管造影(DSA)检查、穿梭箱试验、神经病理检查和胆碱乙酰转移酶(ChAT)免疫组化测定。结果慢性脑血流灌注不足2月后出现明显的认知功能障碍,缺血4月后更明显;海马CA1区ChAT免疫反应阳性神经元分布及其数量较对照组显著减少,且与学习记忆障碍呈正相关。结论多发性脑梗死、进行性的皮层和海马神经元退变以及白质损害是VD的病理基础;额叶皮层和海马胆碱能神经元的损伤可能是认知功能受损害的形态学基础。     

Time-dependent effects of haloperidol and ziprasidone on nerve growth factor, cholinergic neurons, and spatial learning in rats

In this rodent study, we evaluated the effects of different time periods (7, 14, 45, and 90 days) of oral treatment with haloperidol (HAL; 2.0 mg/kg/day) or ziprasidone (ZIP; 12.0 mg/kg/day) on nerve growth factor (NGF) and choline acetyltransferase (ChAT) levels in the hippocampus, and we subsequently assessed water maze task performance, prepulse inhibition (PPI) of the auditory gating response, and several NGF-related proteins and cholinergic markers after 90 days of treatment. Seven and 14 days of treatment with either HAL or ZIP resulted in a notable increase in NGF and ChAT immunoreactivity in the dentate gyrus (DG), CA1, and CA3 areas of the hippocampus. After 45 days, NGF and ChAT immunoreactivity had abated to control levels in ZIP-treated animals, but it was markedly reduced in HAL-treated subjects. After 90 days of treatment, NGF and ChAT levels were substantially lower than controls in both antipsychotic groups. Furthermore, after 90 days of treatment and a drug-free washout period, water maze performance (but not PPI) was impaired in both antipsychotic groups, although the decrement was greater in the HAL group. Several NGF-related and cholinergic proteins were diminished in the brains of subjects treated with either neuroleptic as well. These data support the premise that, although ZIP (given chronically) seems somewhat superior to HAL due to less pronounced behavioral effects and a more delayed appearance of neurochemical deficits, both antipsychotics produce time-dependent deleterious effects on NGF, cholinergic markers (i.e., important neurobiological substrates of memory), and cognitive function.