阿尔茨海默病患者红细胞超氧化物歧化酶与载脂蛋白ε_4等位基因的相互关系

目的　探讨阿尔茨海默病 (AD)患者的外周血氧化应激与载脂蛋白 (apo)Eε4 等位基因的相互关系。方法　分别测定 2 5例散发性AD患者 (AD组 )、2 0例血管性痴呆 (VD)患者、2 2名正常人(正常组 )的红细胞超氧化物歧化酶 (SOD)、血浆一氧化氮 (NO)浓度及apoE等位基因频率。结果　AD组的SOD活性 [U /mg血红蛋白 ]为 10 80± 35 1,明显高于正常组 [(818± 330 )U],P <0 0 5 ;NO浓度的差异无显著性。根据apoEε4 等位基因进行分层后 ,不携带ε4 组间SOD活性差异有显著性 ,AD组高于正常组 (P <0 0 5 )。AD患者的SOD活性与临床痴呆分级量表 (CDR)呈显著性负相关 (r =- 0 480 ,P <0 0 5 ) ,与BLESSED痴呆量表分呈显著性负相关 (r =- 0 5 2 2 ,P <0 0 1) ,正常组的SOD活性与年龄呈显著性负相关 (r=- 0 430 ,P <0 0 5 )。结论　与痴呆严重程度有关的氧化应激可能参与AD患者的病理生理变化 ,并可能受ε4 等位基因的影响     

阿尔茨海默病患者红细胞超氧化物歧化酶与载脂蛋白ε4等位基因的相互关系

目的探讨阿尔茨海默病(AD)患者的外周血氧化应激与载脂蛋白(apo)Eε4等位基因的相互关系.方法分别测定25例散发性AD患者(AD组)、20例血管性痴呆(VD)患者、22名正常人(正常组)的红细胞超氧化物歧化酶(SOD)、血浆一氧化氮(NO)浓度及apoE等位基因频率.结果AD组的SOD活性[U/mg血红蛋白]为1080±351,明显高于正常组[(818±330)U],P＜0.05;NO浓度的差异无显著性.根据apoEε4等位基因进行分层后,不携带ε4组间SOD活性差异有显著性,AD组高于正常组(P＜0.05).AD患者的SOD活性与临床痴呆分级量表(CDR)呈显著性负相关(r=-0.480,P＜0.05),与BLESSED痴呆量表分呈显著性负相关(r=-0.522,P＜0.01),正常组的SOD活性与年龄呈显著性负相关(r=-0.430,P＜0.05).结论与痴呆严重程度有关的氧化应激可能参与AD患者的病理生理变化,并可能受ε4等位基因的影响.     

阿尔采默病和血管性痴呆死亡病例病程分析

目的 分析住院老年痴呆患者起病年龄,死亡年龄及病程。方法 对住院87例痴呆患者起病年龄,死亡年龄,病程进行统计分析,并对阿尔采默病(AD)与血管性痴呆(VD)组间及组内进行对照。结果 AD的起病年龄高于VD(P<0.01),AD的平均死亡年龄大于VD(P值<0.01),AD组的平均病程为(4.0±2.7)年,VD组的平均病程为(4.6±3.8)年,AD与VD的病程无明显差异(P>0.05),AD平均病程女性大于男性(P<0.05),男性平均(3.3±2.1)年,女性(5.3±3.1)年。结论 女性AD的生存时间明显长于男性,AD病人与VD病人存在不同的死亡影响因素。     

载脂蛋白E基因对阿尔茨海默病患者血脂代谢的影响

目的　研究载脂蛋白E(apoE)基因多态性对阿尔茨海默病 (AD)患者血脂代谢的影响。方法　采用限制性片断长度的聚合酶链反应方法对 4 8例AD患者 (AD组 ) ,2 34名非痴呆健康人 (对照组 )的apoE基因频率及基因型分布进行分析。对AD组全部样本和对照组 84名样本的血清apoE、总胆固醇 (TC)、甘油三酯 (TG)、载脂蛋白B(apoB)和载脂蛋白AI(apoAI)浓度进行定量分析 ,将AD组和对照组的血脂分为ε2 、ε3 和ε4组 ,并以ε3 基因为基线 ,分别比较ε2 和ε4基因对血脂代谢的调控作用。结果　对照组apoE基因以ε3 频率为最高 ,其ε3 / 3 基因型最常见 ,其次为ε2 / 3 和ε3 / 4型。AD组ε4基因频率 (0 2 19)明显高于对照组 (0 0 5 1) ,差异有非常显著性 (P <0 0 1)。AD组apoE为 (40± 9)mg/L、TC为 (4 4± 0 7)mmol/L、TG为 (0 99± 0 32 )mmol/L ,均明显低于对照组 [分别为 (44± 10 )mg/L ,(4 7±0 8)mmol/L ,(1 19± 0 87)mmol/L];而apoB浓度 [(0 98± 0 14 )g/L]明显高于对照组 [(0 81± 0 2 0 )g/L];差异有显著性或非常显著性 (P <0 0 5～ 0 0 1)。以ADε3 基因组血脂为基线 ,ε2 基因可以使apoE、TG浓度升高 ,使TC和apoB浓度降低。相反 ,ε4基因可以使apoE、TG浓度下降 ,使TC和apoB浓度升高。结论     

阿尔茨海默病和血管性痴呆患者脑脊液中乙酰胆碱和胆碱检测及其临床意义

目的　探讨阿尔茨海默病 (AD)和血管性痴呆 (VD)患者脑脊液 (CSF)中乙酰胆碱 (ACh)和胆碱 (Ch)含量的异同以及它们与认知障碍的关系。方法　采用简易精神状态量表 (MMSE)对 2 2例AD、2 2例VD和 2 0名对照进行认知功能评分 ,利用高效液相色谱 电化学检测方法 (HPLC ECD)进行CSF的ACh和Ch检测 ,而后进行比较和分析。结果　AD组患者CSF的ACh含量 [(10 .7± 5 .1)nmol/L]低于对照组 [(34 .5± 9.0 )nmol/L](P =0 .0 0 1) ,与MMSE评分呈正相关。VD组患者CSF的ACh含量 [(16 .8± 7.4)nmol/L]也低于对照组 (P =0 .0 0 1) ,与MMSE评分呈正相关。AD组的CSF中Ch含量与对照组相比 [分别为 (6 2 7.6± 145 .1)nmol/L和 (716 .0± 15 9.4)nmol/L],差异无显著意义 ,与MMSE不呈相关关系。VD组患者CSF的Ch含量 [(887.4± 187.4)nmol/L]高于对照组 (P =0 .0 0 2 )和AD组患者 (P =0 .0 0 1)。结论　 (1)ACh的降低与认知障碍呈正相关 ,提示ACh是与记忆有关的重要神经递质 ;(2 )VD的ACh降低提示有与AD类似的发病机制 ;(3)AD患者ACh显著降低和VD患者胆碱显著增高有助于两者之间的鉴别 ;(4 )应用胆碱酯酶抑制剂来提高脑内ACh水平 ,不仅适用于AD ,也适用于VD。     

载脂蛋白E基因多态性与血管性痴呆的相关性研究

目的 探讨载脂蛋白E(apolipoproteinE,apoE)基因多态性与血管性痴呆(vascular Dementia,VD)的相关性。方法 应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术,检测35例VD患者、36例脑梗死(cerebral Infarction,CI)患者以及40名健康人的apoE基因型,同时检测其血脂及载脂蛋白的含量。结果 VD组和CI组患者ε4频率均升高(P<0.01),ε3频率均降低(P<0.05),而两组患者间各等位基因频率差异无统计学意义(P>0.05);apoEε4等位基因携带者总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、apoB水平均较apoEε2、ε3携带者高(P<0.05)。结论 apoE基因多态性与血管性痴呆的发病有关,ε4基因可能为该病的危险因子,且可能与其在脑梗死中的作用机制相似。     

载脂蛋白E基因多态性与Alzheimer病和血管性痴呆的关系

目的 探讨载脂蛋白E(ApoE)基因多态性与Alzheimer病(AD)和血管性痴呆(VD)的关系.方法 用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测79例AD患者(AD组)、85例VD患者(VD组)及156名健康老年人(正常对照组)ApoE基因型和等位基因频率.结果 ApoEε3/ε4基因型及ε4等位基因频率AD组分别为25.3%及17.7%,VD组分别为25.9%及20.5%,正常对照组分别为10.9%及5.7%;AD组及VD组ApoEε3/ε4基因型及ε4等位基因频率显著高于正常对照组(均P＜0.01).结论 ApoEε4等位基因可能是AD和VD共同的危险因素.     

A lzheimer病患者血清IL-2、sIL-2R水平的研究

目的 :Alzheimer病 (AD)是由多种病因引起的涉及多种病理机制和出现多种病理表现的多因素性疾病。近年来研究发现 AD患者血清中细胞因子水平增高以及皮质、海马内神经炎性斑数量增加 ,表明免疫炎症机制在 AD的发生、发展中起重要作用。本研究拟通过对 AD患者血清 IL - 2、 s IL - 2 R水平的检测 ,来探讨其在 AD慢性炎症病理过程中的作用。方法 :采用双抗体酶联免疫吸附试验 (EL ISA) ,检测 10例 AD患者血清 IL 2及 s IL 2 R水平 ,并与血管性痴呆 (VD)组及正常对照组做了比较。结果 :AD组血清中 IL- 2水平为 35 2± 33.4pg/ ml,明显高于 VD组 (2 83.6± 6 2 .9pg/ ml)和正常对照组 (2 5 8.5± 49.1pg/ ml) ,差异显著 (P<0 .0 0 5 ) ;AD组 s IL - 2 R水平为 81± 37.3pmol/ L ,明显高于VD组 (5 4.1± 30 .9pmol/ L )和正常对照组 (48.3± 18.3pmol/ L ) ,差异显著 (P<0 .0 5 )。结论 :说明 AD患者脑内免疫细胞被激活 ,IL- 2、s IL- 2 R参与了 AD的慢性炎症改变过程。血清 IL- 2和 s IL- 2 R可作为检测 AD外周血的免疫标记物。     

经影像学支持的阿尔茨海默病与血管性痴呆的临床比较研究

目的研究阿尔茨海默病(AD)和血管性痴呆(VD)的临床特征,寻找鉴别诊断的有效方法.方法共125例AD患者和97例VD患者,包括北京协和医院的门诊痴呆患者171例和流行病学调查中受访的痴呆患者51例,AD患者均有头颅MRI资料,VD患者都有头颅MRI或CT资料.按照美国精神医学会的<精神障碍诊断和统计手册>第四版(DSM-Ⅳ)标准诊断痴呆,很可能AD采用美国神经病学、语言障碍和卒中-老年性痴呆和相关疾病学会(NINCDS-ADRDA)标准,很可能VD采用美国国立神经病与卒中研究所/瑞士神经科学国际协会(NINDS-AIREN)标准.比较AD和VD患者在认知功能、行为症状、日常活动能力和影像学方面的差异,采用Logistic二元多重回归模型确定鉴别诊断的有效指标.结果不同痴呆阶段的AD和VD患者具有不同的临床特征,两者间的鉴别指标随痴呆进展而变化轻度AD患者学习能力较VD患者减退明显(Fuld物体记忆储存分分别为6.3±2.4、8.0±1.7,P=0.040),鉴别中度AD和VD患者的有效指标是注意力(数字广度测验倒背分分别为2.2±1.4、1.0±1.2,P=0.004)和综合语言能力(简易智能状态检查法综合语言能力分分别为6.3±1.1、5.3±1.7,P=0.001),重度AD患者以短时记忆减退(Fuld物体记忆总分分别为3.1±1.7、6.0±4.3,P=0.046)为著.轻中度AD患者在理财和打电话上逊于VD患者,VD患者则在与肢体活动有关的日常活动中表现退步(均P<0.05).重度VD患者的日常生活活动能力总分明显低于同阶段AD患者(49.3±14.8,62.4±14.9,P=0.032).重复收敛行为是鉴别中重度AD和VD患者的有效指标(均P<0.05).结论 AD和VD具有不同的临床特征.两者的差别是由各自的病变性质、部位和病理生理机制所决定的.     

男性痴呆患者血清性激素的变化

目的:观察阿尔茨海默病(AD)和血管性痴呆(VD)男性患者血清性激素及促性腺激素的变化。方法:老年男性共114人,其中AD 3 2例;VD 3 0例;无痴呆正常老年人5 2名。采用化学发光法测定血中黄体生成素(LH )、促卵泡成熟素(FSH)、雌二醇(E2 )、催乳素(PRL)、睾酮(T)的含量,并计算E2 /T的比值。结果:AD组及VD组患者血清T水平较正常对照组低,差别有显著意义(P <0 .0 5 ,P <0 .0 1)。VD组患者血清E2 /T较正常对照组显著升高;也较AD组明显升高(P <0 .0 1,P <0 .0 5 )。AD、VD组患者血清E2 、LH、FSH、PRL与正常对照组比较,差别均无显著意义(P >0 .0 5 )。结论:老年男性AD及VD患者血清T水平降低。     

Development of the projection from the nucleus of the brachium of the inferior colliculus to the superior colliculus in the ferret

Neurons in the deeper layers of the superior colliculus (SC) have spatially tuned receptive fields that are arranged to form a map of auditory space. The spatial tuning of these neurons emerges gradually in an experience-dependent manner after the onset of hearing, but the relative contributions of peripheral and central factors in this process of maturation are unknown. We have studied the postnatal development of the projection to the ferret SC from the nucleus of the brachium of the inferior colliculus (nBIC), its main source of auditory input, to determine whether the emergence of auditory map topography can be attributed to anatomical rewiring of this projection. The pattern of retrograde labeling produced by injections of fluorescent microspheres in the SC on postnatal day (P) 0 and just after the age of hearing onset (P29), showed that the nBIC-SC projection is topographically organized in the rostrocaudal axis, along which sound azimuth is represented, from birth. Injections of biotinylated dextran amine-fluorescein into the nBIC at different ages (P30, 60, and 90) labeled axons with numerous terminals and en passant boutons throughout the deeper layers of the SC. This labeling covered the entire mediolateral extent of the SC, but, in keeping with the pattern of retrograde labeling following microsphere injections in the SC, was more restricted rostrocaudally. No systematic changes were observed with age. The stability of the nBIC-SC projection over this period suggests that developmental changes in auditory spatial tuning involve other processes, rather than a gross refinement of the projection from the nBIC.     

Mechanisms of the suppression of the nociceptive reflex of the opening of the mouth during stimulation of the structures of the limbic brain

The comparative effectiveness of the inhibitory influence of tetanic stimulation of hypothalamus, amygdala and limbic cortex on EMG-response of m. digastricus evoked by electrical stimulation of tooth pulp nociceptive afferents was studied in cats anesthetized with a mixture of chloralose and nembutal. It was found that inhibition of the EMG-component of the jaw-opening reflex is most pronounced in case of stimulation of medial and lateral region of the hypothalamus, the inhibitory effect of central and medial nuclei of the amygdala is less pronounced and the effect of the limbic cortex is the weakest. It was shown that the mechanism of the antinociceptive effect of tetanic stimulation of the hypothalamus is not related to the concomitant increase of the blood pressure. After stabilization of the blood pressure the suppressive effect of the hypothalamus remains without changes, that points out to a direct, primary, not baro-afferent mechanism of the inhibition of the activity of nociceptive neurons of the trigeminal sensory nuclei. Noradrenaline, injected intravenously, induced a large increase of the blood pressure accompanied by a pronounced inhibition of the pain reflex. Angiotensin causes the same degree of blood pressure elevation without changes in the amplitude of the EMG-response of the pain reflex. Hypothalamic and noradrenergic mechanisms for control of pain sensitivity are discussed.     

The organization of the connections between the cortex and the claustrum in the monkey

The distribution of labelled cells and of extracellular granules in the claustrum has been studied after injections of horseradish peroxidase in several areas of the neocortex. The frontal and parietal lobes are related to the anterior and posterior halves respectively of the claustrum, and the occipital and temporal cortex to the posterior and inferior margins. Parts of the claustrum related to areas of the cortex in the frontal lobe overlap considerably in the antero-posterior dimension with parts related to widely separated but interconnected areas of the parieto-temporal cortex. Areas of cortex within one lobe which are interconnected are related to parts of the claustrum which overlap in the dorsoventral dimension.     

Sexual pheromones and the evolution of the reward system of the brain: the chemosensory function of the amygdala

The amygdala of all tetrapod vertebrates receives direct projections from the main and accessory olfactory bulbs, and the strong similarities in the organization of these projections suggest that they have undergone a very conservative evolution. However, current ideas about the function of the amygdala do not pay sufficient attention to its chemosensory role, but only view it as the core of the emotional brain. In this study, we propose that both roles of the amygdala are intimately linked since the amygdala is actually involved in mediating emotional responses to chemical signals. The amygdala is the only structure in the brain receiving pheromonal information directly from the accessory olfactory bulbs and we have shown in mice that males emit sexual pheromones that are innately attractive for females. In fact, sexual pheromones can be used as unconditioned stimuli to induce a conditioned attraction to previously neutral odorants as well as a conditioned place preference. Therefore, sexual pheromones should be regarded as natural reinforcers. Behavioural and pharmacological studies (reviewed here) have shown that the females' innate preference for sexual pheromones is not affected by lesions of the dopaminergic cells of the ventral tegmental area, and that the systemic administration of dopamine antagonists do not alter neither the attraction nor the reinforcing effects of these pheromones. Anatomical studies have shown that the vomeronasal amygdala gives rise to important projections to the olfactory tubercle and the islands of Calleja, suggesting that these amygdalo-striatal pathways might be involved in the reinforcing value of sexual pheromones.