Notch信号通路在神经干细胞发生中的作用

Notch基因首先由Metz等发现,后因证实该基因功能缺失的果蝇其翅膀边缘会造成一些缺刻表型而得名.研究表明,Notch是一个高度保守的信号通路,广泛表达于无脊椎动物和哺乳动物等多个物种,在多种器官及细胞的发育过程中作为主要的仲裁信号通路决定细胞的命运,并且通过细胞间相互作用的方式精确地调节着细胞的生长、分化及凋亡[1].     

Notch信号在神经系统发育中的多效性

Notch受体介导的信号通路在神经系统发育中发挥着至关重要的作用.Notch是高度保守的信号通路,它通过受体配体的相互作用以及之后的一系列核内分子事件影响相邻细胞的分化命运.以往大量研究结果揭示Notch信号的激活维持了神经干及前体细胞特性,抑制神经元产生并促进胶质细胞生成.最近的研究进展显示Notch信号新的组成分子、新的作用模式、对成熟神经元形态与功能以及对少突胶质细胞生成髓鞘过程的调控作用.综上所述,Notch信号不仅在神经发育中扮演重要角色,还有可能在中枢神经损伤、多发性硬化等疾病的治疗中发挥自己独有的作用,彻底阐明其作用机制在未来对这些疾病新的治疗方法的建立意义重大.本文旨在综述Notch信号在神经系统发育中多方面的功能,并讨论该研究领域的最新进展.     

NOTCH2NLC基因与神经系统疾病的相关性研究进展

Notch信号通路可调控各谱系细胞及组织的分化,参与细胞的增殖、分化、凋亡,决定神经前体细胞增殖和神经元分化的时间和持续时间,其信号通路中某一关键分子突变都有可能导致一系列的神经系统疾病.NOTCH2NL作为Notch信号和神经发生的特异性修饰物,可以激活NOTCH信号通路,参与许多神经变性疾病的生理病理过程.本文就N...     

Notch信号通路在神经干细胞分化与再生的研究进展

Notch信号通路是旁抑制效应调控神经干细胞分化及再生的重要信号通路之一,Notch信号通路维持神经干细胞静态,抑制神经干细胞的分化,对调节神经再生具有重要作用。     

Notch信号通路在神经系统疾病中的研究进展

Notch信号通路调节发育中的多个细胞过程,尤其在神经系统的生长发育中起着重要作用,如调控胶质细胞再生、神经发生、神经突起形成等。因此,Notch信号的异常将导致多种神经系统疾病。本文就Notch信号通路的结构、功能、调节神经系统发育及所致神经系统疾病进行综述。     

Notch信号通路在脑胶质瘤中的研究进展

Notch信号通路通过细胞间受体及配体作用介导信号转导,在系统发育及肿瘤发生、发展等生理病理过程中发挥重要作用。Notch信号通路在脑胶质瘤方面也被广泛研究,Notch配体、受体及其下游基因在脑胶质瘤中都有不同程度的增高,且与胶质瘤级别呈一定的相关性。选择性抑制Notch信号通路,胶质瘤细胞生长受抑、凋亡增加,肿瘤动物模型存活时间延长。最近研究还发现Notch的配体之一DLL4(Deltalike-4)可以抑制肿瘤血管内皮细胞增殖,调控肿瘤血管形成,成为潜在的胶质瘤治疗靶点。     

miRNA与Notch信号通路在心脏发育中的作用

背景：miRNA具有调控细胞增殖、分化和生物体生长发育等功能。Notch信号通路在细胞增殖、分化和器官组织发育也起重要作用。miRNA与Notch信号通路分别在心脏发育中的作用及两者之间关系的研究可能会为干细胞移植治疗某些心脏疾病提供新思路。 目的：综述miRNA和Notch信号通路在心脏发育中作用研究的新进展。 方法：应用计算机在Google Scholar、PubMed数据库和ScienceDirect-Home数据库进行检索,英文检索词“miRNA,Notch signaling pathway,cardiac development,stem cells”。 结果与结论：miRNA通过调节靶基因mRNA或抑制翻译而发挥作用,具有调控细胞增殖、分化等生物学功能,在心脏的发育发挥重要作用。Notch信号通路在决定细胞分化方向和心脏正常发育起重要作用。而miRNA-1可抑制Notch信号中Dll1受体表达而促进小鼠胚胎干细胞向心肌细胞分化。深入了解miRNA或Notch信号通路在心脏发育中的机制及两者之间的联系,明确其在调控干细胞分化为心肌细胞的作用,可能会为干细胞移植治疗某些心脏疾病提供新的干预靶点。     

Notch信号通路与肿瘤血管新生

在无脊椎动物及几乎所有脊椎动物体内,Notch信号通路在细胞分化、发育中发挥关键作用.该通路在进化过程中高度保守,主要功能包括调控细胞间相互作用、维持造血干细胞的自我更新、调节血管新生等.近年的研究发现:Notch信号通路在肿瘤的血管新生过程中也发挥重要作用,与肿瘤生长密切相关.本文就Notch信号通路与血管新生,特别是肿瘤血管新生的关系的研究进展进行综述.     

Notch信号通路在神经系统肿瘤中的研究进展

Notch信号通路（NotchSignalingPathway）在决定细胞生命（包括增殖、分化以及凋亡）过程中发挥着重要作用,其功能异常可以导致细胞恶变和肿瘤形成。同时,针对Notch通路的分子靶向治疗的研究正成为目前肿瘤研究的热点之一。近年来研究表明,Notch信号通路与多种神经系统肿瘤包括垂体腺瘤的发生密切相关。现对Notch信号通路在神经系统肿瘤中的研究进展作一综述。     

Notch信号通路与脑肿瘤

Notch信号通路是一个既简单而又复杂的信号通路,且在多个物种中表达。Notch信号对于细胞的生长发育具有广泛的多样化的影响,可促进或抑制细胞增殖、分化和凋亡。Notch信号通路也与其他关键性的癌通路有较多的相互作用,与一些人类肿瘤的发生发展相关。对于不同的肿瘤,Notch信号既具有促癌作用,也具有抑癌作用。另外,Notch信号对于同一肿瘤的不同级别或不同发展阶段所起的作用也可能不同。经研究表明Notch信号在一些脑肿瘤(脑胶质瘤、髄母细胞瘤、神经母细胞瘤、脑膜瘤)中异常表达,且与这些脑肿瘤的发生发展相关,为脑肿瘤的治疗提供了一个新的有希望的治疗靶点。     

Denervation study of synapses of organ of corti of old world monkeys

Fine structural characteristics of synapses in the spiral organ of Corti were examined, with reference to differences between inner and outer haircell systems, and to location of neurons of origin of efferent axons. Surgical interruption of crossed olivocochlear bundle, of vestibular nerve, of facial nerve, and excision of superior cervical ganglia were used to determine the pathways of efferent axons. Interruption of the vestibular nerve near the brainstem results in degeneration of all efferent terminals on outer hair cells. Mid-line lesions at, and caudal to, the facial colliculus result in degeneration of about half of these efferent terminals. Efferent synaptic bulbs to the inner hair-cell system are small, of the order of one micron, and form type 2 junctions with afferent dendrites. They tend to have more large dense-core vesicles (about 80 nm) than the large efferent terminals of the outer hair-cell system, and appear to be the terminals of axons in the habenula perforata, which exhibit varicosities laden with large dense core vesicles. The varicosities are unaffected by excision of the superior cervical ganglia. So far as our material can reveal, it appears that the varicosities in the habenula perforata do not survive vestibular root interruption, nor do the efferent processes in the internal spiral bundle or at the base of inner hair cells. Most interestingly, the afferent processes of the inner hair-cell system, as identified for example by their relation to pre-synaptic bodies in the inner hair cells, are subject to a trans-synaptic reaction after severance of the vestibular root. They undergo a dramatic cytological transformation, characterized by increase of volume, engorgement with microtubules, microfilaments, microvesicles of various sizes, and clusters of lysosomes. Thus, both the efferent and afferent terminals of the inner hair-cell system show marked cytological differences from the corresponding terminals of the outer hair cell system.     

Mechanism of action of tubocurarine on nicotinic cholinoreceptors of neurons of the sympathetic ganglia of rats

Tubocurarine (Tc) effect on membrane currents elicited by acetylcholine (ACh) was studied in isolated superior cervical ganglion neurons of rat using patch-clamp method in the whole-cell recording mode. The "use-dependent" block of ACh current by Tc was revealed in the experiments with ACh applications, indicating that Tc blocked the channels opened by ACh. Mean lifetime of Tc-open channel complex, tau, was found to be 9.8 +/- 0.5 s (n = 7) at -50 mV and 20-24 degrees C. tau exponentially increased with membrane hyperpolarization (e-fold change in tau corresponded to the membrane potential shift by 61 mV). Inhibition of the ACh-induced current by Tc (3-30 microM/1) was completely abolished by membrane depolarization to the level of 80-100 mV. Inhibition of ACh-induced current was augmented at increased ACh doses. It is concluded that the open channel block produced by Tc is likely to be the only mechanism for Tc action on nicotinic acetylcholine receptors in superior cervical ganglion neurons of rat.     

The effect of age of onset of PD on risk of dementia

Background Dementia occurs in the majority of patients with Parkinson’s disease (PD). Late onset of PD has been reported to be associated with a higher risk for dementia. However, age at onset (AAO) and age at baseline assessment are often correlated. The aim of this study was to explore whether AAO of PD symptoms is a risk factor for dementia independent of the general effect of age. Methods Two community-based studies of PD in New York (n = 281) and Rogaland county, Norway (n = 227) and two population-based groups of healthy elderly from New York (n = 180) and Odense, Denmark (n = 2414) were followed prospectively for 3–4 years and assessed for dementia according to DSM-IIIR. All PD and control cases underwent neurological examination and were followed with neurological and neuropsychological assessments. We used Cox proportional hazards regression based on three different time scales to explore the effect of AAO of PD on risk of dementia, adjusting for age at baseline and other demographic and clinical variables. Findings In both PD groups and in the pooled analyses, there was a significant effect of age at baseline assessment on the time to develop dementia, but there was no effect of AAO independent of age itself. Consistent with these results, there was no increased relative effect of age on the time to develop dementia in PD cases compared with controls. Interpretation This study shows that it is the general effect of age, rather than AAO that is associated with incident dementia in subjects with PD. Received in revised form: 22 December 2005     

Limits of deinstitutionalization--perspectives of relatives of psychiatric patients

After a hopeful beginning, the social process of the reintegration of those with severe mental illness has come to a standstill. I am led to wonder whether "the community" really wants to live together with people suffering from severe mental illness, and if so, how closely? As long as the medical treatment of mental illness provided by the general practitioners is fundamentally deficient, as they are not able to prescribe the necessary interventions--such as out-patient psychiatric nursing, and service providers in the out-patient sector are content with offering increasingly intensive forms of care for the less seriously ill at the cost of the Social Welfare System--the reintegration of those with serious mental illness remains an illusion--which is mainly to the benefit of providers of residential care in homes and hostels.     

Sense of coherence as a predictor of subjective state of health: results of 4 years of follow-up of adults

A number of cross-sectional population studies have shown that a strong sense of coherence (SOC) is associated with various aspects of good perceived health. The association does not seem to be entirely attributable to underlying associations of SOC with other variables, such as age or level of education. OBJECTIVE: The aim of the study reported here was to determine whether SOC predicted subjective state of health. METHODS: The study was carried out as a two-way panel mail survey of 1976 individuals with 4 years interval for two collections of data. The statistical method used was multivariate cumulative logistic modeling. Age, initial subjective state of health, initial occupational training level, and initial degree of social integration were included as potential explanatory variables. RESULTS: A strong SOC predicted good health in women and men. CONCLUSIONS: SOC can be interpreted as an autonomous internal resource contributing to a favorable development of subjective state of health. SOC data should, however, be regarded as complementary to and not a substitute for information already known to be associated with increased risk of future ill health.