脑啡肽酶(Neprilysin)与老年痴呆

阿尔茨海默氏病(Alzheimer's disease,AD)是一种多发生在老年的中枢神经系统退行性疾病。其发病机制尚未阐明。细胞外淀粉样β蛋白(amyloidβ-protein,Aβ)沉积是AD主要病理学特征之一。体内Aβ的稳态水平取决于Aβ合成和分解活动之间的代谢平衡。几乎在所有家族性AD中,Aβ合成代谢增加被认为是引起Aβ沉积的主要原因,但在散发AD中较少证据支持Aβ生成增多的作用。因此,近年来Aβ降解减少在AD中的作用逐渐引起人们的重视。与Aβ降解有关的酶也得到了广泛的研究。Neprilysin(NEP),也称脑啡肽酶。本世纪以来,它在Aβ分解代谢中的作…     

β淀粉样蛋白在阿尔茨海默病发病中的相关性研究

阿尔茨海默病(AD)是一种常见的中枢神经系统退行性疾病,β淀粉样蛋白(Aβ)在AD的发生和发展中起着关键性作用,Aβ沉积可引起突触和线粒体结构及功能的一系列改变,研究Aβ在AD发病中的作用及相关性,对AD的治疗有指导意义。     

脑啡肽酶与金属元素关系的研究进展

脑啡肽酶(Neprilysin,NEP)属于哺乳动物膜金属肽酶家族,是一种膜结合型的金属蛋白酶.已知NEP是脑内主要的Aβ降解酶,并且被认为在AD的病理过程中起到关键作用.它可以与锌离子配位,其活性依赖于锌离子的存在,而且受到其他某些金属离子的调节.金属元素与体内有机配体所形成的配位化合物在很多生命活动中起到重要作用,本文就NEP的结构和活性与金属元素锌、铜、镉的关系作一综述.     

阿尔茨海默病中β-淀粉样蛋白清除机制的研究进展

β-淀粉样蛋白(Aβ)形成的斑块沉积是阿尔茨海默病(AD)的一个特征性病理改变。在早发型和散发型AD患者脑中均可出现Aβ清除障碍。了解Aβ清除途径的具体机制对寻找有效的AD治疗策略至关重要。本文将对Aβ细胞内降解清除途径、血脑屏障转运清除途径、脑间质液泵流清除途径及脑脊液吸收清除途径的具体机制作一综述。     

阿尔茨海默病β淀粉样蛋白清除研究

正阿尔茨海默病(Alzheimer disease,AD)是一种以进行性认知功能障碍及行为损害为特征的中枢神经系统退行性疾病,是痴呆最常见的类型,可分为家族性AD和散发性AD[1]。两种类型的AD均以β淀粉样蛋白(amyloid-β,Aβ)过度累积为特点,有学说认为AD的发生是Aβ生成与清除失衡     

免疫治疗阿尔茨海默病的研究及其意义

阿尔茨海默病(AD)是一种神经退行性疾病,其显著病理特征之一为患者脑内产生由42个氨基酸构成的β-淀粉样蛋白(β-amyloid protein,Aβ42),目前认为Aβ42的纤维化和沉积是AD发生和发展的一个主要因素.该文就以减轻脑内Aβ42的负荷、阻止和逆转Aβ42的纤维化和沉积为最终目标的免疫治疗AD的主要方法、效果以及其研究意义进行综述,为相关领域的研究者提供参考.     

Alzheimer病与免疫治疗(综述)

A1zheimer病(AD)是一种以进行性记忆障碍和智能衰退为主要临床特征的中枢神经系统退行性疾病，病因复杂．涉及多种病理机制。研究表明β淀粉样蛋白(Aβ)可能是各种原因诱发AD的共同通路，是AD形成和发展的关键因素。免疫炎症机制在AD发生发展过程中具有重要作用。因此．探索用免疫的方法治疗AD已受到广泛关注。     

α-分泌酶与阿尔茨海默病的治疗

淀粉样前体蛋白(APP)在脑内经β和γ分泌酶的作用生成β淀粉样蛋白(Aβ),也可在α和γ分泌酶的作用下从Aβ序列内部进行降解,生成sAPPα而避免Aβ的生成,sAPPα可对神经细胞产生神经营养和神经保护作用。Aβ在脑内沉积从而对细胞造成毒性作用即Aβ毒性学说被认为是阿尔茨海默病(AD)发病机制之一。目前AD的治疗策略主要集中于抑制β分泌酶和γ分泌酶的研究。新近的研究显示,一类属于解聚素和金属蛋白酶(主要指ADAM10、ADAM17和ADAM9)分子具有α分泌酶的功能,提高α分泌酶的表达可以降低Aβ,有可能在AD的治疗中具有潜在作用。     

脂质筏在阿尔茨海默病发病机制中的作用

β淀粉样蛋白(Aβ)是阿尔茨海默病(AD)的特征病理改变之一,Aβ的产生和聚集是AD发生和进展的重要因素之一.脂质筏为膜脂双层内含有特殊脂质和蛋白质的微区,具有低流动性,呈现有序液相,富含胆固醇,鞘脂和神经节苷酯GM1.细胞膜的脂质筏参与Aβ的产生及Aβ聚集形成低聚体,脂质筏及其组成成份的异常影响Aβ的产生及Ap聚集形成低聚体.以脂质筏为靶点可能为AD患者的治疗提供一种新的途径,选择性干预APP在脂质筏内的加工过程以调节Aβ的生成可能为一种有效的治疗方法.     

MicroRNAs与阿尔茨海默病的研究进展

<正>阿尔茨海默病(Alzheimer’s disease,AD)是一种起病隐匿的进行性发展的神经系统退行性疾病。AD的发病机制目前尚不十分清楚,其典型的神经病理学改变是:β-淀粉样蛋白(amyloidβ,Aβ)沉积、过度磷酸化的微管相关蛋白tau及神经元的损伤和缺失等。microRNAs(miRNAs)是在真核生物中发现的一类内源性的具有调控功能的非编码RNA,可以指导沉默复合体降解靶信使核糖核酸(Messenger RNA,mR-     

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.     

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.     

A projection to the striatum from the medial subdivision of the posterior group of the thalamus in the cat

Injections of wheat germ agglutinin-conjugated horseradish peroxidase in the lateral part of the caudate nucleus or the putamen of the cat result in retrograde thalamic cell-labeling in the rostral extension of the medial subdivision of the posterior group (POM). Autoradiography after [³H]amino acid injection of POM reveals a dense and discontinuous distribution of axons in the lateral half of the caudate and putamen concentrated at their middle rostrocaudal levels. This newly discovered thalamostriatal projection of POM may account for somatosensory activity observed in striatal cells.     

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.     

Evidence for the collateral innervation of the esophagus and the heart from neurons in the compact formation of the nucleus ambiguus of the rat

We investigated whether the heart receives collateral projections from the neurons which innervate the esophagus with a retrograde double-labeling method using two fluorescent tracers. Following injections of True Blue (TB) into the esophagus and Diamidino Yellow (DY) into the heart, about 21.9% of the labeled esophageal motoneurons in the compact formation of the nucleus ambiguus (AmC) were retrogradely double labeled. No single-labeled cardiac motoneurons were found in the AmC. The present results provide anatomical substrates for the esophagocardiac reflex.     

Role of the paraventricular nucleus in the projection from the nucleus of the solitary tract to the olfactory bulb

Electrophysiological experiments were performed on anesthetized rats to determine the effects of lesions of the paraventricular nucleus on the amplitude of evoked potentials recorded in the periglomerular layer of the olfactory bulb after nucleus of the solitary tract electrical stimulation. Lesions of the paraventricular nucleus enhance the amplitude of both the positive and negative components of the evoked potential in the olfactory bulb. The pathway from the paraventricular nucleus to the olfactory bulb seems to exert a suppressive influence over the projection from the nucleus of the solitary tract to the olfactory bulb under these conditions.     

On the origin of the serotonergic input to the intermediate lobe of the rat pituitary

Single stimulations of the vagina and cervix were performed between proestrus and the first day of diestrus with a stimulator designed to grade the intravaginal penetration of a rod. The percent incidence of pseudopregnancy after this stimulation was exponentially related to the extent of intravaginal penetration and was also affected by the stage of the cycle at which the stimulation was performed. At 10.00 h on proestrus, an exponential increase in the incidence of pseudopregnancy was observed with shallow penetrations, while an exponential decrease was found when deeper penetrations were applied. Such negative exponential correlation had disappeared at 22.00 h on proestrus. At that time, also, some responses were elicited by very shallow penetrations (17 mm) and all the animals responded to penetrations of 20 mm or more. Sensitivity to cervicovaginal stimulation at 10.00 h on estrus was lower than that at 22.00 h on proestrus and it was even lower at 10.00 h on the first day of diestrus. The response to 18 mm of penetration was studied every 3 h between 10.00 h on proestrus and 10.00 h on estrus, and then every 12 h until 10.00 h on the first day of diestrus. This stimulation was usually ineffective to induce pseudopregnancy, except for a brief period encompassing the night between proestrus and estrus, when a peak in the incidence of responses was reached. This peak sensitivity could be advanced following the s.c. administration of 250 and 500 ng of LH-RH at 11.00 h on proestrus. Other doses were ineffective. The peptide (500 ng) was unable to induce pseudopregnancy in rats that received no cervicovaginal stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

On the development of the stratification of the inner plexiform layer in the chick retina

This study investigated the development of the subdivision of the chick inner plexiform layer (IPL). The approach included an immunohistological analysis of the temporal and spatial expressions of choline acetyltransferase, of the neural-glial-related and neural-glial cell adhesion molecules (NrCAM and NgCAM, respectively) and axonin-1, and of inwardly rectifying potassium (Kir) channels in 5- to 19-day-old (E5-E19) embryos. Ultrastructural investigations evaluated whether synaptogenesis accompanies the onset of differentiation of the IPL. We found that the differentiation of the IPL started at E9. Distinct cholinergic strata appeared, NrCAM immunoreactivity showed a poorly defined stratification, and Kir3.2 was expressed in the IPL and in the inner nuclear layer. From E10 until late E14, NgCAM- and axonin-1-immunoreactive strata emerged in an alternating sequence from the outer to the inner IPL. During this period, the NrCAM pattern sharpened, and eventually five bands of weaker and stronger immunoreactivity were found. Conventional synapses formed at the beginning of E9, and stratification of the IPL also began on the same day at the same location. Synaptogenesis and stratification followed a gradient from the central to the peripheral retina. The topographic course of differentiation of the IPL generally corresponded to the course of maturation of ganglion and amacrine cells. Synaptogenesis and the expression of G-protein-gated Kir3.2 channels accompanied the onset of stratification. These events coincide with the occurrence of robust and rhythmic spontaneous neuronal activity. The subsequent differentiation of the IPL seemed to be orchestrated by several mechanisms.