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Hippocampal cell loss and neurogenesis after fetal alcohol exposure: Insights from different rodent models 胎儿酒精暴露后海马细胞损失和神经发生:来自不同啮齿动物模型的见解
Pub Date : 2010-09-24 DOI: 10.1016/j.brainresrev.2010.04.011
Joana Gil-Mohapel , Fanny Boehme , Leah Kainer , Brian R. Christie

Prenatal ethanol exposure is invariably detrimental to the developing central nervous system and the hippocampus is particularly sensitive to the teratogenic effects of ethanol. Prenatal ethanol exposure has been shown to result in hippocampal cell loss, altered neuronal morphology and impaired performance on hippocampal-dependent learning and memory tasks in rodents. The dentate gyrus (DG) of the hippocampus is one of the few brain regions where neurogenesis continues into adulthood. This process appears to have functional significance and these newly generated neurons are believed to play important functions in learning and memory. Recently, several groups have shown that adult hippocampal neurogenesis is compromised in animal models of fetal alcohol spectrum disorders (FASD). The direction and magnitude of any changes in neurogenesis, however, appear to depend on a variety of factors that include: the rodent model used; the blood alcohol concentration achieved; the developmental time point when alcohol was administered; and the frequency of ethanol exposure. In this review we will provide an overview of the different rodent models of FASD that are commonly used in this research, emphasizing each of their strengths and limitations. We will also present an up-to-date summary on the effects of prenatal/neonatal ethanol exposure on adult hippocampal neurogenesis and cell loss, highlighting some of the possible molecular mechanisms that might be involved.

产前乙醇暴露对发育中的中枢神经系统总是有害的,海马体对乙醇的致畸作用特别敏感。产前乙醇暴露已被证明会导致啮齿动物海马细胞丢失、神经元形态改变和海马依赖性学习和记忆任务的表现受损。海马的齿状回(DG)是少数几个神经发生持续到成年的大脑区域之一。这个过程似乎具有功能意义,这些新产生的神经元被认为在学习和记忆中起着重要的作用。最近,一些研究小组发现,胎儿酒精谱系障碍(FASD)的动物模型中,成年海马神经发生受到损害。然而,神经发生变化的方向和幅度似乎取决于多种因素,包括:所使用的啮齿动物模型;血液酒精浓度达到;给予酒精的发育时间点;以及接触乙醇的频率。在这篇综述中,我们将提供在本研究中常用的不同啮齿动物FASD模型的概述,强调它们各自的优势和局限性。我们还将介绍关于产前/新生儿乙醇暴露对成年海马神经发生和细胞损失影响的最新总结,强调可能涉及的一些可能的分子机制。
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引用次数: 185
Looking at the blood–brain barrier: Molecular anatomy and possible investigation approaches 观察血脑屏障:分子解剖学和可能的研究方法
Pub Date : 2010-09-24 DOI: 10.1016/j.brainresrev.2010.05.003
Filipa Lourenço Cardoso, Dora Brites, Maria Alexandra Brito

The blood–brain barrier (BBB) is a dynamic and complex interface between blood and the central nervous system that strictly controls the exchanges between the blood and brain compartments, therefore playing a key role in brain homeostasis and providing protection against many toxic compounds and pathogens. In this review, the unique properties of brain microvascular endothelial cells and intercellular junctions are examined. The specific interactions between endothelial cells and basement membrane as well as neighboring perivascular pericytes, glial cells and neurons, which altogether constitute the neurovascular unit and play an essential role in both health and function of the central nervous system, are also explored. Some relevant pathways across the endothelium, as well as mechanisms involved in the regulation of BBB permeability, and the emerging role of the BBB as a signaling interface are addressed as well. Furthermore, we summarize some of the experimental approaches that can be used to monitor BBB properties and function in a variety of conditions and have allowed recent advances in BBB knowledge. Elucidation of the molecular anatomy and dynamics of the BBB is an essential step for the development of new strategies directed to maintain or restore BBB integrity and barrier function and ultimately preserve the delicate interstitial brain environment.

血脑屏障(BBB)是血液和中枢神经系统之间的一个动态和复杂的界面,严格控制血液和脑区间的交换,因此在大脑稳态中起关键作用,并提供对许多有毒化合物和病原体的保护。本文综述了脑微血管内皮细胞和细胞间连接的独特特性。内皮细胞与基底膜以及邻近的血管周围周细胞、胶质细胞和神经元之间的特定相互作用,共同构成神经血管单位,在中枢神经系统的健康和功能中发挥重要作用,并进行了探讨。一些相关的内皮通路,以及参与血脑屏障通透性调节的机制,以及血脑屏障作为信号接口的新作用。此外,我们总结了一些实验方法,可用于监测血脑屏障的性质和功能在各种条件下,并允许在血脑屏障知识的最新进展。阐明血脑屏障的分子解剖学和动力学是开发维持或恢复血脑屏障完整性和屏障功能的新策略的必要步骤,并最终保护微妙的脑间质环境。
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引用次数: 535
Language comprehension in the bilingual brain: fMRI and ERP support for psycholinguistic models 双语脑的语言理解:功能磁共振成像和ERP对心理语言学模型的支持
Pub Date : 2010-09-01 DOI: 10.1016/j.brainresrev.2010.03.002
Walter J.B. van Heuven , Ton Dijkstra

In this paper, we review issues in bilingual language comprehension in the light of functional magnetic resonance imaging (fMRI) and event-related brain potential (ERP) data. Next, we consider to what extent neuroimaging data are compatible with assumptions and characteristics of available psycholinguistic models of bilingual word processing, in particular the BIA+ model. We argue that this model provides a theoretical framework that is useful for interpreting both the spatial brain activation patterns observed with fMRI and the temporal brain wave patterns of ERP studies. Finally, we demonstrate that neuroimaging data stimulate the specification of hitherto only globally described components of functional psycholinguistic models.

本文从功能磁共振成像(fMRI)和事件相关脑电位(ERP)数据的角度综述了双语语言理解的相关问题。接下来,我们考虑神经成像数据在多大程度上与现有双语文字处理心理语言学模型的假设和特征兼容,特别是BIA+模型。我们认为,该模型为解释fMRI观察到的空间脑激活模式和ERP研究的时间脑电波模式提供了一个有用的理论框架。最后,我们证明,神经成像数据刺激规范迄今为止只有全球描述的功能心理语言模型的组成部分。
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引用次数: 196
Between molecules and experience: Role of early patterns of coordinated activity for the development of cortical maps and sensory abilities 在分子和经验之间:协调活动的早期模式在皮层地图和感觉能力发展中的作用
Pub Date : 2010-09-01 DOI: 10.1016/j.brainresrev.2010.03.005
Ileana L. Hanganu-Opatz

Sensory systems processing information from the environment rely on precisely formed and refined neuronal networks that build maps of sensory receptor epithelia at different subcortical and cortical levels. These sensory maps share similar principles of function and emerge according to developmental processes common in visual, somatosensory and auditory systems. Whereas molecular cues set the coarse organization of cortico-subcortical topography, its refinement is known to succeed under the influence of experience-dependent electrical activity during critical periods. However, coordinated patterns of activity synchronize the cortico-subcortical networks long before the meaningful impact of environmental inputs on sensory maps. Recent studies elucidated the cellular and network mechanisms underlying the generation of these early patterns of activity and highlighted their similarities across species. Moreover, the experience-independent activity appears to act as a functional template for the maturation of sensory networks and cortico-subcortical maps. A major goal for future research will be to analyze how this early activity interacts with the molecular cues and to determine whether it is permissive or rather supporting for the establishment of sensory topography.

处理来自环境的信息的感觉系统依赖于精确形成和完善的神经网络,这些神经网络在不同的皮层下和皮层水平上构建感觉受体上皮的图谱。这些感觉地图具有相似的功能原理,并根据视觉、体感和听觉系统共同的发育过程出现。虽然分子线索设置皮质-皮质下地形的粗糙组织,但已知其细化在关键时期依赖经验的电活动的影响下成功。然而,在环境输入对感觉地图产生有意义的影响之前,协调的活动模式就会使皮质-皮质下网络同步。最近的研究阐明了这些早期活动模式产生的细胞和网络机制,并强调了它们在物种间的相似性。此外,经验独立活动似乎是感觉网络和皮质-皮质下映射成熟的功能模板。未来研究的一个主要目标将是分析这种早期活动如何与分子线索相互作用,并确定它是允许的还是支持感官地形的建立。
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引用次数: 121
Distinct patterns of neuronal inputs and outputs of the juxtaparaventricular and suprafornical regions of the lateral hypothalamic area in the male rat 雄性大鼠下丘脑外侧区室旁旁区和皮层上区神经元输入和输出的不同模式
Pub Date : 2010-09-01 DOI: 10.1016/j.brainresrev.2010.02.002
Joel D. Hahn, Larry W. Swanson

We have analyzed at high resolution the neuroanatomical connections of the juxtaparaventricular region of the lateral hypothalamic area (LHAjp); as a control and in comparison to this, we also performed a preliminary analysis of a nearby LHA region that is dorsal to the fornix, namely the LHA suprafornical region (LHAs). The connections of these LHA regions were revealed with a coinjection tract-tracing technique involving a retrograde (cholera toxin B subunit) and anterograde (Phaseolus vulgaris leucoagglutinin) tracer. The LHAjp and LHAs together connect with almost every major division of the cerebrum and cerebrospinal trunk, but their connection profiles are markedly different and distinct. In simple terms, the connections of the LHAjp indicate a possible primary role in the modulation of defensive behavior; for the LHAs, a role in the modulation of ingestive behavior is suggested. However, the relation of the LHAjp and LHAs to potential modulation of these behaviors, as indicated by their neuroanatomical connections, appears to be highly integrative as it includes each of the major functional divisions of the nervous system that together determine behavior, i.e., cognitive, state, sensory, and motor. Furthermore, although a primary role is indicated for each region with respect to a particular mode of behavior, intermode modulation of behavior is also indicated. In summary, the extrinsic connections of the LHAjp and LHAs (so far as we have described them) suggest that these regions have a profoundly integrative role in which they may participate in the orchestrated modulation of elaborate behavioral repertoires.

我们以高分辨率分析了下丘脑外侧区室旁旁区(LHAjp)的神经解剖学连接;作为对照,与此相比,我们还对穹窿背侧附近的LHA区域进行了初步分析,即LHA皮质上区(LHAs)。这些LHA区域的连接是通过一种包括逆行(霍乱毒素B亚基)和顺行(Phaseolus vulgaris白细胞凝集素)示踪剂的共注射示踪技术显示的。LHAjp和lha几乎连接到大脑和脑脊干的每一个主要分支,但它们的连接特征明显不同。简而言之,LHAjp的连接表明在防御行为的调节中可能起主要作用;对于lha,它可能在摄食行为的调节中起作用。然而,LHAjp和lha与这些行为的潜在调节之间的关系,正如它们的神经解剖学联系所表明的那样,似乎是高度整合的,因为它包括神经系统中共同决定行为的每个主要功能部门,即认知、状态、感觉和运动。此外,虽然指出了每个区域在特定行为模式方面的主要作用,但也指出了行为的模间调制。总之,LHAjp和lha的外在联系(到目前为止我们已经描述了它们)表明,这些区域具有深刻的整合作用,它们可能参与精心设计的行为谱的精心调节。
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引用次数: 109
Traumatic brain injury, major depression, and diffusion tensor imaging: Making connections 创伤性脑损伤、重度抑郁症和弥散张量成像:建立联系
Pub Date : 2010-09-01 DOI: 10.1016/j.brainresrev.2010.04.003
Jerome J. Maller , Richard H.S. Thomson , Philip M. Lewis , Stephen E. Rose , Kerstin Pannek , Paul B. Fitzgerald

It is common for depression to develop after traumatic brain injury (TBI), yet despite poorer recovery, there is a lack in our understanding of whether post-TBI brain changes involved in depression are akin to those in people with depression without TBI. Modern neuroimaging has helped recognize degrees of diffuse axonal injury (DAI) as being related to extent of TBI, but its ability to predict long-term functioning is limited and has not been considered in the context of post-TBI depression. A more recent brain imaging technique (diffusion tensor imaging; DTI) can measure the integrity of white matter by measuring the directionality or anisotropy of water molecule diffusion along the axons of nerve fibers. Aim: To review DTI results in the TBI and depression literatures to determine whether this can elucidate the etiology of the development of depression after TBI. Method: We reviewed the TBI/DTI (40 articles) and depression/DTI literatures (17 articles). No articles were found that used DTI to investigate depression post-TBI, although there were some common brain regions identified between the TBI/DTI and depression/DTI studies, including frontotemporal, corpus callosum, and structures contained within the basal ganglia. Specifically, the internal capsule was commonly reported to have significantly reduced fractional anisotropy, which agrees with deep brain stimulation studies. Conclusion: It is suggested that measuring the degree of DAI by utilizing DTI in those with or without depression post-TBI, will greatly enhance prediction of functional outcome.

创伤性脑损伤(TBI)后出现抑郁症是很常见的,尽管恢复较差,但我们对创伤性脑损伤后与抑郁症相关的大脑变化是否与未患TBI的抑郁症相似尚缺乏了解。现代神经影像学已经帮助识别弥漫性轴索损伤(DAI)的程度与TBI的程度有关,但其预测长期功能的能力有限,尚未考虑在TBI后抑郁的背景下。一种较新的脑成像技术(弥散张量成像;DTI可以通过测量水分子沿神经纤维轴突扩散的方向性或各向异性来测量白质的完整性。目的:回顾DTI结果在脑外伤和抑郁症的文献,以确定这是否可以阐明脑外伤后抑郁症发展的病因。方法:回顾TBI/DTI(40篇)和抑郁症/DTI(17篇)相关文献。虽然在TBI/DTI和抑郁/DTI研究中发现了一些共同的大脑区域,包括额颞叶、胼胝体和基底神经节内的结构,但没有发现使用DTI来研究脑外伤后抑郁的文章。具体来说,通常报道的内囊具有显著降低的分数各向异性,这与深部脑刺激研究一致。结论:应用DTI测量脑外伤后伴有或不伴有抑郁的患者DAI程度,可大大提高功能预后的预测。
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引用次数: 99
Free colour illustrations in the online version of articles 免费彩色插图在文章的在线版本
Pub Date : 2010-09-01 DOI: 10.1016/S0165-0173(10)00060-3
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引用次数: 0
Targets and consequences of protein SUMOylation in neurons 神经元中SUMOylation蛋白的目标和后果
Pub Date : 2010-09-01 DOI: 10.1016/j.brainresrev.2010.04.002
Kevin A. Wilkinson, Yasuko Nakamura, Jeremy M. Henley

The post-translational modification of proteins is critical for the spatial and temporal regulation of signalling cascades. This is especially important in the CNS where the processes affecting differentiation, growth, targeting and communication between neurones are highly complex and very tightly regulated. In recent years it has emerged that modification of proteins by members of the SUMO (small ubiquitin-related modifier) family of proteins play key roles in neuronal function. SUMOylation involves the covalent conjugation of a member of the SUMO family to lysine residues in target proteins. Multiple nuclear and perinuclear SUMOylation targets have been reported to be involved in nuclear organisation and transcriptional regulation. In addition, a growing number of extranuclear SUMO substrates have been identified that can have important acute effects on neuronal function. The SUMOylation of both intra- and extranuclear proteins have been implicated in a diverse array of processes that have far-reaching implications for neuronal function and pathophysiology. Here we review the current understanding of the targets and consequences of protein SUMOylation in the brain and examine its established and potential involvement in a wide range of neurological and neurodegenerative diseases.

蛋白质的翻译后修饰对于信号级联的空间和时间调节至关重要。这在中枢神经系统中尤为重要,因为中枢神经系统中影响神经元分化、生长、靶向和交流的过程非常复杂,并且受到严格的调控。近年来,人们发现SUMO(小泛素相关修饰因子)蛋白家族成员对蛋白质的修饰在神经元功能中起着关键作用。SUMO酰基化涉及SUMO家族成员与靶蛋白赖氨酸残基的共价偶联。据报道,多个核和核周SUMOylation靶点参与核组织和转录调控。此外,越来越多的核外SUMO底物已经被确定,可以对神经元功能有重要的急性影响。核内蛋白和核外蛋白的sumo化与一系列不同的过程有关,这些过程对神经元功能和病理生理具有深远的影响。在这里,我们回顾了目前对大脑中蛋白质SUMOylation的目标和后果的理解,并研究了它在广泛的神经和神经退行性疾病中的既定和潜在参与。
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引用次数: 133
Genetic influences on cognitive functions in the elderly: A selective review of twin studies 遗传对老年人认知功能的影响:对双胞胎研究的选择性回顾
Pub Date : 2010-09-01 DOI: 10.1016/j.brainresrev.2010.02.001
Teresa Lee , Julie D. Henry , Julian N. Trollor , Perminder S. Sachdev

In this review, we examined the published reports on the heritability of cognitive functioning in old age. Twenty-four papers from five study centers, comprising of participants with a mean age of 65 years and above were examined. The comparability of findings from different studies was compromised by the use of different measures for the same cognitive domain, and with large scale twin studies in cognitive aging limited to a few Scandinavian countries. While the results from cross-sectional samples appear to lend support for the notion that heritability of cognitive functions decreases in the elderly, the findings are best considered inconclusive. Longitudinal reports show little evidence for genetic effects, but an increase in unique environmental influences on the rate of cognitive change as age increases. In relation to the two prominent theories of cognitive aging, the genetic influence on processing speed as a major contributor to cognitive aging has been indicated in three reports, whereas the genetic relationship between executive functions and other cognitive functions has not been explored. Only two studies have focused on sex difference and did not find sex-specific genetic influence in cognitive abilities. This review indicates that there are complex relationships between heritability, environmental influence, and cognitive functions in the elderly. It highlights the need for more research, with consistent and appropriate cognitive measures, with data obtained from larger and more geographically and culturally diverse twin samples.

在这篇综述中,我们检查了已发表的关于老年认知功能遗传性的报告。来自五个研究中心的24篇论文,包括平均年龄在65岁及以上的参与者。不同研究结果的可比性受到对同一认知领域使用不同测量方法的影响,并且在认知衰老方面的大规模双胞胎研究仅限于少数斯堪的纳维亚国家。虽然来自横断面样本的结果似乎支持认知功能的遗传性在老年人中下降的观点,但这些发现最好被认为是不确定的。纵向报告显示遗传影响的证据很少,但随着年龄的增长,独特的环境影响对认知变化率的影响有所增加。在认知衰老的两大理论中,遗传对处理速度的影响是认知衰老的主要因素,已有三篇报道指出,而执行功能与其他认知功能之间的遗传关系尚未得到探讨。只有两项研究关注性别差异,并没有发现性别特异性基因对认知能力的影响。这一综述表明,遗传力、环境影响和老年人认知功能之间存在复杂的关系。它强调需要进行更多的研究,采用一致和适当的认知措施,并从更大、更地理和文化多样化的双胞胎样本中获得数据。
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引用次数: 66
Electrophysiological measures as potential biomarkers in Huntington's disease: Review and future directions 电生理测量作为亨廷顿病的潜在生物标志物:综述和未来方向
Pub Date : 2010-09-01 DOI: 10.1016/j.brainresrev.2010.03.004
Lan Nguyen , John L. Bradshaw , Julie C. Stout , Rodney J. Croft , Nellie Georgiou-Karistianis

Neuroimaging is fundamental to identifying quantifiable and objective biomarkers in symptomatic and pre-diagnostic Huntington's disease (HD). However, the challenge remains to find reliable biomarkers with high sensitivity and specificity that can be used to track the functional decline over time and test efficacy of therapeutic intervention. While many recent studies have focused on neuroimaging techniques based on brain hemodynamic activity, comparatively fewer have utilized electroencephalography (EEG) and event-related potentials (ERPs). This review aims to summarise and integrate key electroencephalographical findings from the last two decades in symptomatic and pre-diagnostic HD, in context with recent neuroimaging data, and to use this information to identify promising candidate markers for future research and clinical consideration.

神经影像学是识别症状和诊断前亨廷顿舞蹈病(HD)可量化和客观生物标志物的基础。然而,挑战仍然是找到可靠的生物标志物,具有高灵敏度和特异性,可用于跟踪功能衰退随着时间的推移和测试治疗干预的有效性。虽然最近的许多研究都集中在基于脑血流动力学活动的神经成像技术上,但相对较少使用脑电图(EEG)和事件相关电位(ERPs)。本综述旨在总结和整合过去二十年来在症状性和诊断前HD中的关键脑电图发现,并结合最近的神经影像学数据,并利用这些信息确定有希望的候选标记物,用于未来的研究和临床考虑。
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引用次数: 49
期刊
Brain Research Reviews
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