山参、园参、西洋参和红参的超氧化物歧化酶活性比较

目的:对山参、园参、西洋参及红参水提取物进行超氧化物歧化酶(SOD)活性比较研究,为人参药材的质量评价和临床应用提供依据。方法:采用考马斯亮蓝法测定4种参水提取物中蛋白含量,采用改良的邻苯三酚自氧化法分别测定4种参的SOD活力,采用聚丙烯酰胺凝胶电泳及NBT显色法进行4种参的酶活显示。结果:山参、园参、西洋参的SOD活力分别为109.642,16.048,7.612U.mg-1,红参SOD活力几乎为零。结论:4种参的SOD活力不同,其中山参的酶活力最高。     

PPARγ agonist pioglitazone improves scopolamine-induced memory impairment in mice

Objectives This study was conducted to evaluate the effects of exposure to pioglitazone, a peroxisome proliferator‐activated receptor agonist, on cognitive impairment induced by scopolamine, a muscarinic antagonist, in mice. Methods Pioglitazone (9 mg/kg, 18 mg/kg) was orally administered for 9 days at 30 min before intraperitoneal injection with scopolamine (0.8 mg/kg, i.p.). Cognitive function was evaluated by the passive avoidance test and the Morris water maze test on the 10th day after treatment. Changes in cholinergic system reactivity were also examined by measuring the acetylcholine, acetylcholinesterase and choline acetyltransferase in the hippocampus and cortex. Key findings Scopolamine injection induced impaired performance in the passive avoidance test and the water maze test and severe decrease of cholinergic system reactivity, as indicated by reduced acetylcholine levels, decreased choline acetyltransferase activity and increased acetylcholinesterase activity. Daily administration of pioglitazone significantly increased step‐through latency in passive avoidance test, and significantly decreased the escape latency, and increased the time spent in the platform quadrant in the Morris water maze test. Pioglitazone also protected against scopolamine‐induced cholinergic system deficit, including reduced acetylcholine levels, decreased choline acetyltransferase activity and increased acetylcholinesterase activity in the hippocampus or cortex. Conclusions Pioglitazone demonstrates a significant neuroprotective effect against scopolamine‐induced cholinergic system deficit and cognitive impairment.     

Cognition enhancement by the acetylcholine releaser DuP 996

DuP 996, 3,3,-Bis(4-pyridinylmethyl)-1-phenylindolin-2-one, a potent in vitro and in vivo releaser of acetylcholine (ACh), dopamine (DA), and serotonin (5HT) in rat brain, significantly enhanced the performance of rats and mice in several behavioral test procedures. At doses of 0.01–0.1 mg/kg s.c. DuP 996 protected against a hypoxia-induced passive avoidance deficit in rats. In active avoidance procedures, DuP 996 enhanced acquisition of responses: in rats, at doses between 0.085 and 0.85 mg/kg s.c. and 0.25 and 0.85 mg/kg p.o.; in mice, at doses between 0.85 and 2.5 mg/kg s.c. These effects occurred without any alteration of sensitivity to foot-shock. In addition, Dup 996 prevented a CO₂-induced retention deficit of a passive avoidance response when administered prior to acquisition testing. In a test for acquisition of lever pressing for food in the rat, DuP 996 increased the proportion of animals acquiring this response. Thus, DuP 996 was active in both the shock- and appetitive-motivated procedures and was shown to enhance performance levels when administered post-training as well as before training trials. These results suggest that DuP 996 may be useful in the treatment of cognition dysfunction.     

阿尔采末病胆碱能学说研究进展

中枢胆碱能系统参与调节哺乳动物的神经元兴奋性、皮质可塑性以及学习记忆过程 ,与脑认知功能密切相关。阿尔采末病 (Alzheimersdisease ,AD)是老年性痴呆的最常见原因 ,主要表现为进行性的认知功能下降。基底前脑胆碱能损伤导致的中枢胆碱能系统功能低下是AD患者认知功能障碍的基础。在AD病程中存在一个恶性循环 ,即脑内的胆碱能神经传递早期受损 ,导致神经退行性病变的易损区内Aβ的大量产生以及tau蛋白过度磷酸化 ,而Aβ又进一步削弱胆碱能神经传递的效应 ,中枢胆碱能功能障碍可能是AD患者认知功能障碍的根源     

梓醇对D-半乳糖致亚急性衰老小鼠学习记忆及脑中相关抗氧化酶活性的影响

目的观察梓醇对D-半乳糖(D-gal)致亚急性衰老小鼠学习记忆及脑组织中相关抗氧化酶活性的影响。方法用D-gal皮下注射制备衰老小鼠模型,同时在前两周和后两周分别皮下注射给予梓醇(2.5 mg/kg),检测小鼠学习记忆能力和大脑皮层、海马中丙二醛(MDA)水平,超氧化物岐化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)活性。结果衰老模型组小鼠空间学习记忆能力下降,逃避潜伏期较正常对照组明显延长,脑中SOD、GSH-PX活性降低,MDA含量增高。给予梓醇预防和治疗后可以改善衰老模型小鼠的学习记忆能力,并显著提高脑中SOD、GSH-PX活性,降低MDA水平。结论梓醇可改善D-gal致衰老小鼠的学习记忆障碍,此作用可能与梓醇的抗氧化作用有关。     

Improvement of cognitive functions by the acetylcholine releaser SM 21

The effect of administration of SM 21 on memory processes was evaluated in the mouse passive avoidance and in the rat social learning tests. SM 21 (10–20 mg kg⁻¹ i.p.) prevented amnesia induced by scopolamine and dicyclomine as tested by the mouse passive avoidance test and prevented memory disruption by AF‐64A and benehexol ascertained by the rat passive avoidance test. Both SM 21 enantiomers were able to abolish dicyclomine‐induced amnesia in mice. SM 21, starting from the dose of 10 mg kg⁻¹ i.p., antagonized the memory impairment produced by mecamylamine, baclofen, and diphenhydramine in mice, as well as amnesia induced by diazepam in rats. SM 21, at doses ranging between 10 and 30 mg kg⁻¹ i.p., prevented memory reduction in mice by hypoxia in the passive avoidance test. In the social learning test, SM 21 (10 mg kg⁻¹ i.p.) injected in adult rats reduced the duration of active exploration of a familiar partner in the second session of the test. SM 21 prevented amnesia in both mice and rats comparable to that of the cholinesterase inhibitor physostigmine (0.2 mg kg⁻¹ i.p.), the M1 selective agonist AF‐102B (10 mg kg⁻¹ i.p.), and the nootropic drug piracetam (30 mg kg⁻¹ i.p.). These results demonstrated the ability of SM 21 to modulate memory functions and suggests that SM 21 could be useful in the treatment of cognitive deficits. Drug Dev. Res. 47:118–126, 1999. © 1999 Wiley‐Liss, Inc.     

尼莫地平对癫痫大鼠海马突触后致密物95表达的影响

目的探讨尼莫地平(nimodipin,NIM)对戊四氮(Pen-tylenetetrazol,PTZ)点燃癫痫大鼠空间学习记忆能力及海马突触后致密物95(postsynaptic density95,PSD-95)表达的影响。方法动物分为正常对照组、PTZ组和NIM组,采用PTZ慢性点燃癫痫模型,应用Morris水迷宫观察各组大鼠空间学习记忆能力,Western blot及反转录多聚酶链反应(RT-PCR)方法检测各组大鼠海马PSD-95蛋白和PSD-95 mRNA的表达。结果PTZ致痫组大鼠空间学习记忆能力受损,其海马PSD-95蛋白水平及PSD-95 mRNA表达较对照组明显减少(P<0·05);与PTZ组比较,NIM组大鼠空间学习记忆能力好转,其海马PSD-95蛋白水平及PSD-95 mRNA表达均升高(P<0·05)。结论PTZ点燃癫痫大鼠存在空间学习记忆受损,可能与PSD-95表达减少有关;NIM可以提高PSD-95的表达,改善癫痫大鼠的学习记忆能力。     

Early‐life exposure to low levels of permethrin exerts impairments in learning and memory with the effects on neuronal and glial population in adult male mice

Permethrin, a pyrethroid chemical, is widely used as a pesticide because of its rapid insecticidal activity. Although permethrin is considered to exert very low toxicity in mammals, the effects of early, low‐level, chronic exposure on the adult central nervous system are unclear. In this study, we investigated the effects of low‐level, chronic permethrin exposure in early life on the brain functions of adult mice, using environmentally relevant concentrations. We exposed mice to the acceptable daily intake level of permethrin (0.3 ppm) in drinking water during the prenatal and postnatal periods. We then examined the effects on the central nervous system in adult male offspring. In the permethrin group, we detected behavior that displayed incomplete adaptation to a novel environment, as well as an impairment in learning and memory. In addition, immunohistochemical analysis revealed an increase in doublecortin‐ (an immature neuron marker) positive cells in the hippocampal dentate gyrus in the permethrin exposure group compared with the control group. Additionally, in the permethrin exposure group there was a decrease in astrocyte number in the hilus of the dentate gyrus, and remaining astrocytes were often irregularly shaped. These results suggest that exposure to permethrin at low levels in early life affects the formation of the neural circuit base and behavior after maturation. Therefore, in the central nervous system of male mice, low‐level, chronic permethrin exposure during the prenatal and postnatal periods has effects that were not expected based on the known effects of permethrin exposure in mature animals.     

类叶升麻苷对东莨菪碱所致记忆获得性障碍的改善作用

目的　观察类叶升麻苷对小鼠学习记忆能力的影响。方法　用东莨菪碱致小鼠记忆获得性障碍模型 ,以行为学实验 (跳台法、水迷路法 )、大脑皮层和纹状体乙酰胆碱酯酶活性和M受体的最大结合力为指标观察类叶升麻苷的作用。结果　在东莨菪碱致小鼠记忆障碍模型中 ,类叶升麻苷可延长跳台实验的平台停留期 ,并显著减少错误次数 ;在水迷路实验中可提高正确反应百分率 ;并能拮抗东莨菪碱所引起的大脑皮层乙酰胆碱酯酶的增高及皮层、纹状体M受体最大结合力的降低。结论　类叶升麻苷对东莨菪碱所引起的小鼠学习记忆能力障碍有改善作用 ,其作用机制可能与抑制乙酰胆碱酯酶活性和激动M受体的作用有关     

中枢认知功能有关基因

中枢学习记忆功能障碍是衰老及老年性痴呆病人的典型特征之一。大量研究初步表明中枢学习记忆的生理和病理过程受基因调控,已发现多种基因及其产物与中枢学习记忆的生理及病理过程有密切的关系。即刻早期基因家族作为“第三信使”参与调节神经细胞内信号转导而与学习记忆密切相关,其中ｃ ｆｏｓ的表达与学习记忆功能的变化具有密切关系。神经细胞粘附分子、ｅｐｅｎｄｙｍｉｎ及ＧＡＰ ４３基因参与和影响突触的可塑性与重建及细胞间粘附连接。ＣＲＥＢ能激活与学习记忆密切相关的基因,在长时记忆（ＬＴＭ）过程中起重要作用。此外,ｂｃｌ ２、ＩＣＥ、ｐ５３、及ｈｓｐ等基因参与了神经元的信号转导及凋亡等过程,与学习记忆过程也有一定的联系。因此,寻找和研究学习记忆功能有关基因对从基因水平阐明中枢学习记忆功能的调控机制具有重要意义。     

Effect of chronic treatment of carvedilol on oxidative stress in an intracerebroventricular streptozotocin induced model of dementia in rats

Objectives Oxidative stress is emerging as an important issue in the pathogenesis of dementia. This study was conducted to investigate the possible neuroprotective effects of carvedilol against streptozotocin induced behavioural alterations and oxidative damage in rats. Methods An intracerbroventricular cannula was implanted in the lateral ventricles of male Wistar rats. Various behavioural (locomotor activity, Morris water maze task) and biochemical parameters (lipid peroxidation, nitrate concentration, catalase, acetylcholinesterase, reduced glutathione and protein) were assessed. Key findings Intracerebroventricular administration of streptozotocin caused a significant memory deficit as evaluated in the Morris water maze task paradigms, and caused marked oxidative damage as indicated by significant increases in malondialdehyde and nitrite levels, and depletion of superoxide dismutase, catalase and reduced glutathione levels. It also caused a significant increase in acetylcholinesterase activity. Chronic administration of carvedilol (1 and 2 mg/kg, i.p.) for a period of 25 days starting 4 days before streptozotocin administration resulted in an improvement in memory retention, and attenuation of oxidative damage and acetylcholinesterase activity. Conclusions This study demonstrates the effectiveness of carvedilol in preventing cognitive deficits as well as the oxidative stress caused by intracerbroventicular administration of streptozotocin in rats. Carvedilol may have potential in the treatment of neurodegenerative diseases.     

当归芍药散对脑缺血再灌注所致记忆损伤模型小鼠的影响

目的：观察当归芍药散（DSS）对脑缺血再灌注所致记忆损伤模型的影响。方法：建立小鼠脑缺血再灌注损伤模型,采用避暗实验小鼠记忆功能,并观察DSS对其影响,同时测定小鼠脑内Ca-ATP酶活性、NO含量,蛋白质含量及脑指数、胸腺指数、脾脏指数等。结果：DSS可明显延长脑缺血再灌注损伤模型小鼠避暗潜伏期,明显抑制模型小鼠脑内Ca-ATP酶活性、脑指数及蛋白质含量的降低,明显降低脑内升高的NO含量,对脑缺血再灌所致小鼠脾脏萎缩有显著恢复作用。结论：DSS可能通过升高蛋白质含量、抑制脑萎缩、减轻钙离子超载等环节改善脑缺血再灌注损伤所致小鼠记忆障碍。     

Effect of combination of extracts of ginseng and ginkgo biloba on acetylcholine in amyloid beta-protein-treated rats determined by an improved HPLC

AIM: To determine the concentration of acetylcholine (ACh) in amyloid beta-protein (Abeta) treated rats and offer a method determining ACh as well. METHODS: A 1-month combination of extrats of ginseng and ginkgo biloba (Naoweikang) ig administration to rats was performed daily after bilateral injection of Abeta(1-40) (4 g/L, 1 microL for each side) into hippocampus. After decollation, homogenizing, and centrifuging and extracting, a high pressure liquid chromatographic (HPLC) method using electrochemical detection (ECD) combined with two immobilized enzyme reactors was used to determine ACh in rat whole brain. RESULTS: With a mobile phase consisting of disodium hydrogen orthophosphate, tetramethylammonium chloride (TMACl), octanesulfonic acid sodium salt (OSA) and "Reagent MB" at a final pH of 8.0, ACh was determined while removing the interfering choline in less than 10 min at a flow rate of 0.35 mL/min on a platinum (Pt) working electrode at a potential of +300 mV vs a solid-state palladium (Pd) reference electrode. Linear regression analysis of peak area vs concentration demonstrated linearity in the 28.01 to 1400.06 microg/L injection range. The r-value was 0.9978. The limit of detection (LOD) is 0.28 ng on column. ACh in whole brain decreased by 20.34 % (from 162.1+/-32.7 to 134.7+/-14.0 microg/L, P<0.05) after bilateral injection of Abeta into rat hippocampus. After Naoweikang administration (31 and 15.5 mg/kg, respectively), ACh increased by 19.97 % (from 134.7+/-14.0 to 161.6+/-26.2 microg/L, P<0.05) and 18.56 % (from 134.7+/-14.0 to 159.7+/-22.9 microg/L, P<0.05), respectively. CONCLUSION: Naoweikang significantly increased the level of ACh in whole brain of Abeta treated rats. And a sensitive, selective and reliable method for routinely determining ACh in rat whole brain was established in this study.     

天冰调督胶囊改善癫痫大鼠学习、记忆及对海马ChAT、AchE表达的影响

目的探讨天冰调督胶囊对癫痫认知学习记忆改变的影响.方法Sprague-Dawley大鼠腹腔注射印防己毒素(1.5 mg·kg-1·d-1)连续30d,制作反复发作癫痫模型,点燃模型随机分为模型组、天冰调督胶囊低、高(1.2,4.8 g·kg-1)剂量组、吡拉西坦组、丙戊酸钠和吡拉西坦组,各组均qd灌胃给药,连续给药28 d,以Morris水迷宫观察各组大鼠的空间学习记忆能力、免疫组织化学方法观察海马ChAT、AchE的表达变化.结果经过30 d点燃癫痫大鼠再观察治疗28 d,与正常组相比,模型组大鼠空间记忆能力明显降低(P＜0.01),海马CA1区胆碱乙酰转移酶(ChAT)免疫反应阳性数量显著减少,CA2区乙酰胆碱酯酶(AchE)免疫反应阳性数量增多(P＜0.05);天冰调督胶囊观察组学习记忆指标以及ChAT、AchE的表达,与模型组相比有不同程度改善(P＜0.05,P＜0.01).结论天冰调督胶囊可在一定程度上改善反复发作后癫痫大鼠的学习记忆能力.     

An investigation of the range of cognitive impairments induced by scopolamine 0·6 mg s.c

The present study was conducted to determine the degree to which impairments in attention accompany the memory deficits produced by scopolamine. Eighteen healthy young volunteers received scopolamine 0·6 mg subcutaneously on three experimental sessions and placebo on three others. On each session, prior to, and 60 min after injection, the subjects underwent an automated computerized battery of 11 cognitive tasks. The study was run double-blind and the order of treatment conditions over successive visits was counterbalanced between subjects. Scopolamine produced marked and significant decrements on all major aspects of performance from the battery. The drug lowered the efficiency of the detection and processing of information in tests of visual vigilance, rapid information processing, choice reaction, letter cancellation and logical reasoning. These effects were accompanied by a lowering of critical flicker-fusion frequency and subjective alertness. Memory was also impaired on tests of immediate recall, delayed recall, recognition and memory scanning. These findings confirm and extend previous work, demonstrating that scopolamine impairs the selection and evaluation of environmental information, as well as reducing the likelihood of information being subsequently recalled or recognized. Whether the former effects contribute to the latter is not known, but this must be considered a possibility. This potential role of processing deficits in memory loss associated with cholinergic blockade is briefly considered in relation to the cholinergic hypothesis of geriatric memory loss.