编者按: 脑与认知科学研究的现状与前沿

研究和揭示大脑在生理和病理状态下的工作机制,一直是脑与认知科学的重要研究内容和目标.虽然脑与认知科学领域已经取得了一系列重要的研究成果,但仍然面临巨大的挑战.因此,各国都在加大投入,推动技术创新,开展多学科交叉、多层次的脑与认知科学研究.2013年美国启动脑科学     

Somatostatin Binding Sites in Human and Monkey Brain: Localization and Characterization

A radioiodinated analogue of somatostatin 28, 125I [Leu8,D-Trp22,Tyr25] SS-28, was used to localize and characterize somatostatin binding sites in both human and monkey brain. High-affinity binding sites (approximately 1 nM) were found in cerebral cortex. The highest binding was in cerebral cortex with intermediate binding found in hippocampus, striatum, and amygdala and low binding in hypothalamus and brainstem. There was a rough correlation between somatostatin receptor binding and concentrations of somatostatin-like immunoreactivity (SLI) in human brain. Somatostatin receptors were stable for up to 24 h in an animal model simulating human autopsy conditions and there was no correlation between postmortem interval and receptor binding in human brain. Pharmacologic characterization in human cortex showed that there was a correlation between the inhibition of receptor binding by somatostatin analogues and their known abilities to inhibit growth hormone secretion. These findings demonstrate that a highly specific membrane-associated receptor for somatostatin is present in both monkey and human brain. Examination of somatostatin receptor binding in Alzheimer's disease and Huntington's disease may improve understanding of the role of somatostatin in both these illnesses.     

Cerebral cartography and connectomics

Cerebral cartography and connectomics pursue similar goals in attempting to create maps that can inform our understanding of the structural and functional organization of the cortex. Connectome maps explicitly aim at representing the brain as a complex network, a collection of nodes and their interconnecting edges. This article reflects on some of the challenges that currently arise in the intersection of cerebral cartography and connectomics. Principal challenges concern the temporal dynamics of functional brain connectivity, the definition of areal parcellations and their hierarchical organization into large-scale networks, the extension of whole-brain connectivity to cellular-scale networks, and the mapping of structure/function relations in empirical recordings and computational models. Successfully addressing these challenges will require extensions of methods and tools from network science to the mapping and analysis of human brain connectivity data. The emerging view that the brain is more than a collection of areas, but is fundamentally operating as a complex networked system, will continue to drive the creation of ever more detailed and multi-modal network maps as tools for on-going exploration and discovery in human connectomics.     

Problems of ontogeny and phylogeny in brain-size evolution

Fundamental ambiguities in the interpretation of brain/body allometric trends can only be resolved by analyzing relationships between ontogenetic brain/body growth processes in different groups. The ambiguous concept of adult encephalization confuses at least three distinct types of transformation of a common mammalian growth curve: scalar magnification, total curve didplacement, and changes in proportions of the pre- and postnatal phases of the curve. The conservative ratio between pre- and postnatal growth phases determines the apparent linearity of comparative brain/body allometry and can be explained by assuming that embyological neurogenetic processes ultimately determine both target brain and body size—the first directly and the second indirectly via neurohormonal regulation of somatic growth. Uneven taxonomic distribution of different ontogenetic growth patterns may explain many differences in the allometric trends at different taxonomic levels of analysis. The human brain grows exactly as if it was in a giant ape body; however, because of decoupled growth in different brain regions, it regulates body growth as though it were the size of a chimpanzee brain. Human encephalization exhibits an ontogenetic transformation not found in other mammalian groups.     

Trophic factors and cell therapy to stimulate brain repair after ischaemic stroke

Brain repair involves a compendium of natural mechanisms that are activated following stroke. From a therapeutic viewpoint, reparative therapies that encourage cerebral plasticity are needed. In the last years, it has been demonstrated that modulatory treatments for brain repair such as trophic factor- and stem cell-based therapies can promote neurogenesis, gliogenesis, oligodendrogenesis, synaptogenesis and angiogenesis, all of which having a beneficial impact on infarct volume, cell death and, finally, and most importantly, on the functional recovery. However, even when promising results have been obtained in a wide range of experimental animal models and conditions these preliminary results have not yet demonstrated their clinical efficacy. Here, we focus on brain repair modulatory treatments for ischaemic stroke, that use trophic factors, drugs with trophic effects and stem cell therapy. Important and still unanswered questions for translational research ranging from experimental animal models to recent and ongoing clinical trials are reviewed here.     

Astrocytes in injury states rapidly produce anti-inflammatory factors and attenuate microglial inflammatory responses

Microglia are known to be a primary inflammatory cell type in the brain. However, microglial inflammatory responses are attenuated in the injured brain compared to those in cultured pure microglia. In the present study, we found that astrocytes challenged by oxygen-glucose deprivation (OGD) or H(2) O(2) released soluble factor(s) and attenuated microglial inflammatory responses. Conditioned medium prepared from astrocytes treated with OGD (OGD-ACM) or H(2) O(2) (H(2) O(2) -ACM) significantly reduced the levels of interferon-γ (IFN-γ)-induced microglial inflammatory mediators, including inducible nitric oxide synthase, at both the mRNA and protein levels. The anti-inflammatory effect of astrocytes appeared very rapidly (within 5min), but was not closely correlated with the extent of astrocyte damage. Both OGD-ACM and H(2) O(2) -ACM inhibited STAT nuclear signaling, as evidenced by a reduction in both STAT-1/3 binding to the IFN-γ-activated site and IFN-γ-activated site promoter activity. However, both phosphorylation and nuclear translocation of STAT-1/3 was unchanged in IFN-γ-treated microglia. The active component(s) in OGD-ACM were smaller than 3kDa, and displayed anti-inflammatory effects independent of protein synthesis. These results suggest that, in the injured brain, astrocytes may act as a controller to rapidly suppress microglial activation.     

PTD-BDNF融合基因克隆、表达和纯化

构建含蛋白转导结构域(PTD)与脑源性神经营养因子(BDNF)融合基因的质粒,并在大肠肝菌中表达。用PCR扩增PTD-BDNF融合基因,经DNA测序无误后插入表达质粒pJW2构建质粒pJPB,转化大肠杆菌并进行PTD-BDNF蛋白的诱导表达和纯化。结果DNA序列分析表明构建含有PTD-BDTF融合基因的质粒与设计相同,PTD-BDNF融合蛋白在大肠杆菌中获得表达并进一步纯化。     

Effects of domestication on brain structure and behavior in mammals

The domestication of mammals has led to a reduction of brain size in general. There are, however, species-specific differences concerning the degree of mass decrease. Certain parts of the brains are also involved to different degrees but altogether rather unique effects are characteristic for domesticated mammals at different evolutionary levels. These changes in brain size and proportions are compared with behavioral changes due to domestication. They are valued as a result of artificial selection according to human demands, and thus, in zoological terms, they are interpreted as intraspecific adaptations to the special «ecological niche» of domestication.     

Influence of acclimation and determination temperature on the oxygen consumption of the brain in two species of anurans

1. 1. The effects of sudden changes by increasing or decreasing the measurement temperature on the oxygen consumption of the brains of Bufo arenarum and Leptodactylus ocellatus were determined.

2. 2. The experiments were carried at in vitro at temperatures which range from 4 to 37°C. The brain was oxygenated and stabilized for 20 min at each of the temperatures to which it was subjected before oxygen consumption measurements were made.

3. 3. A theoretical curve representing the variation of oxygen consumption with temperature was calculated according to the following exponential relationship; for Leptodactylus ocellatus y = 0.408 × 1.07^x and for Bufo arenarum y = 0.389 × 1.065^x.

4. 4. These results were compared with the brain oxygen consumption of animals acclimated to different temperatures, whose oxygen consumption was measured at a fixed temperature. Only Leptodactylus ocellatus had a significantly lower oxygen consumption in a high range of temperatures, indicating thermal compensation, probably to save metabolic reserves.

5. 5. No deterioration of the brain tissue was observed, as several passages from high to low temperatures in the range of 20°–30°C, showed a reversible oxygen consumption in acclimated and non-acclimated Bufo arenarum and Leptodactylus ocellatus.

孤独症谱系障碍的遗传基础与神经机制

孤独症谱系障碍(autism spectrum disorder,ASD)是一种神经精神障碍,主要表现为社会交往障碍、交流障碍以及局限性的兴趣和重复刻板的行为模式三个主要核心症状．本文介绍了ASD的遗传基础和神经机制的最新研究进展．ASD具有较高的遗传率,且ASD个体的5-羟色胺和睾丸激素都较高．神经影像学研究发现,ASD个体的杏仁核、扣带回、梭状回、镜像神经元和前额叶等大脑区域在结构和功能上都与正常发育个体存在差异,但在个别区域激活模式的差异方向上仍存在不一致的地方．此外,功能连接的研究结果也证实了ASD个体连接不良的假设．未来的研究应该更多地着眼于如何利用这些基础研究成果为临床上提出有效的治疗和训练方式．     

Comparative study between 4-aminobutyrate-2-oxoglutarate aminotransferase (GABA-T) from rat forebrain and cerebellum

In this study differences in the biochemical properties of 4-aminobutyric acid aminotransferase (GABA-T) from forebrain and cerebellum were detected. These differences may be related to: a) the characteristics of the catalytic site, b) the substrate affinities and c) their pyridoxal-phosphate requirements which suggests that PLP could be a physiological regulator of these forms of brain GABA-T.     

发展性阅读障碍的脑机制——来自脑成像研究的证据

发展性阅读障碍是一种特殊的学习障碍,发展性阅读障碍的脑机制一直是研究者们关心的一个重要问题．随着脑成像技术的应用,人们在发展性阅读障碍的脑机制研究方面取得了重大进展．脑结构研究发现,发展性阅读障碍者在颞-顶叶、颞-枕叶、额下回、小脑等区域都存在一定的脑结构异常,这些脑结构异常要么表现在某个脑区的结构上,要么表现某个脑区结构的左右不对称性上．脑功能研究发现,发展性阅读障碍者出现脑结构异常的区域也大多表现出脑功能的异常．脑功能连接的研究发现,发展性阅读障碍者脑功能连接的异常不仅涉及到同侧脑区前后部分的连接,还涉及双侧脑区相应部分的连接．另外,中文发展性阅读障碍的研究发现了与拼音文字发展性阅读障碍不同的脑机制．这些研究成果为进一步揭示发展性阅读障碍的脑机制以及拓展中文发展性阅读障碍的研究提供了借鉴．     

Regional and Subcellular Calmodulin Content of Rat Brain

Calmodulin contents of cortex, cerebellum, striatum, diencephalon, and medulla + pons and of subcellular fractions of each region were determined by radioimmunoassay. The diencephalon had the highest level of calmodulin (48.87 +/- 4.56 micrograms/mg protein), whereas medulla + pons had the lowest level (8.01 +/- 0.84 micrograms/mg protein). In all brain regions, the mitochondrial fraction was richest in calmodulin (from 71 to 227 micrograms/mg protein) whereas other areas contained from 6 to 66 micrograms/mg protein.     

Administration of Myo-inositol Plus Ethanolamine Elevates Phosphatidylethanolamine Plasmalogen in the Rat Cerebellum

Plasmalogens are ether-linked phospholipids highly abundant in nervous tissue. Previously we demonstrated that acute administration of myo-inositol (myo-Ins) + [2-¹³C] ethanolamine ([2-¹³C]Etn) significantly elevated phosphatidylethanolamine plasmalogen (PlsEtn) in rat whole brain. Current experiments investigated the effects of acute myo-Ins+[2-¹³C]Etn administration on [PlsEtn] and the biosynthesis of new Etn lipids using NMR spectroscopy in rat cerebral cortex, hippocampus, brainstem, midbrain and cerebellum. Treated rats received a single dose of myo-Ins+[2-¹³C]Etn and controls received saline rather than myo-Ins. Data reveal that the cerebellum is the brain region most affected by treatment, which resulted in a 22% increase in [PlsEtn] and 89% increase in newly synthesized Etn lipids relative to controls (P 0.05). Furthermore, the cerebellar PlsEtn/phosphatidylethanolamine ratio and molar percentage of PlsEtn were significantly elevated by 12% and 8%, respectively (P 0.05). These data suggest that myo-Ins influences Etn lipid metabolism in brain, particularly in the cerebellum where there is a stimulation in the biosynthesis of new Etn lipids with a preference towards PlsEtn.     

Blood-brain barrier modeling with co-cultured neural progenitor cell-derived astrocytes and neurons

In vitro blood-brain barrier (BBB) models often consist of brain microvascular endothelial cells (BMECs) that are co-cultured with other cells of the neurovascular unit, such as astrocytes and neurons, to enhance BBB properties. Obtaining primary astrocytes and neurons for co-culture models can be laborious, while yield and heterogeneity of primary isolations can also be limiting. Neural progenitor cells (NPCs), because of their self-renewal capacity and ability to reproducibly differentiate into tunable mixtures of neurons and astrocytes, represent a facile, readily scalable alternative. To this end, differentiated rat NPCs were co-cultured with rat BMECs and shown to induce BBB properties such as elevated trans-endothelial electrical resistance, improved tight junction continuity, polarized p-glycoprotein efflux, and low passive permeability at levels indistinguishable from those induced by primary rat astrocyte co-culture. An NPC differentiation time of 12 days, with the presence of 10% fetal bovine serum, was found to be crucial for generating NPC-derived progeny capable of inducing the optimal response. This approach could also be extended to human NPC-derived astrocytes and neurons which similarly regulated BBB induction. The distribution of rat or human NPC-derived progeny under these conditions was found to be a roughly 3 : 1 mixture of astrocytes to neurons with varying degrees of cellular maturity. BMEC gene expression analysis was conducted using a BBB gene panel, and it was determined that 23 of 26 genes were similarly regulated by either differentiated rat NPC or rat astrocyte co-culture while three genes were differentially altered by the rat NPC-derived progeny. Taken together, these results demonstrate that NPCs are an attractive alternative to primary neural cells for use in BBB co-culture models.     

Selenium and selenoproteins in the brain and brain diseases

Over the past three decades, selenium has been intensively investigated as an antioxidant trace element. It is widely distributed throughout the body, but is particularly well maintained in the brain, even upon prolonged dietary selenium deficiency. Changes in selenium concentration in blood and brain have been reported in Alzheimer's disease and brain tumors. The functions of selenium are believed to be carried out by selenoproteins, in which selenium is specifically incorporated as the amino acid, selenocysteine. Several selenoproteins are expressed in brain, but many questions remain about their roles in neuronal function. Glutathione peroxidase has been localized in glial cells, and its expression is increased surrounding the damaged area in Parkinson's disease and occlusive cerebrovascular disease, consistent with its protective role against oxidative damage. Selenoprotein P has been reported to possess antioxidant activities and the ability to promote neuronal cell survival. Recent studies in cell culture and gene knockout models support a function for selenoprotein P in delivery of selenium to the brain. mRNAs for other selenoproteins, including selenoprotein W, thioredoxin reductases, 15-kDa selenoprotein and type 2 iodothyronine deiodinase, are also detected in the brain. Future research directions will surely unravel the important functions of this class of proteins in the brain.     

Permeable Endothelium and the Interstitial Space of Brain

1. Fenestrated vessels can be reversibly induced in brain by agents that stimulate urokinase production. This plasminogen activator, like vascular endothelial growth factor and metalloproteinases, is secreted by tumor cells and may account for induction of fenestrated vessels. Why only some of the brain's barrier vessels are converted to fenestrated vessels is unknown.2. The structures responsible for the filtering of solutes by fenestrated vessels may be the same as those of continuous, less permeable vessels: the glycocalyx on the surfaces of the endothelial cells and the subendothelial basal lamina.3. Solutes leaving the cerebral ventricles immediately enter the interstitial clefts between the cells lining the ventricles. A fraction of a variety of solutes, injected into CSF compartments, is retained by subendothelial basal lamina, from which the solutes may be released in a regulated way.4. The brain's CSF and interstitial clefts are the conduits for nonsynaptic volume transmission of diffusible signals, e.g., ions, neurotransmitters, and hormones. This type of transmission could be abetted by a parallel, cell-to-cell volume transmission mediated by gap junctions between astrocytes bordering CSF compartments and parenchymal astrocytes.5. The width and contents of the interstitial clefts in fetal brain permit cell migration and outgrowth of neurites. The contents of the narrower and different interstitial clefts of mature brain permit solute convection but must be enzymatically degraded in order for cells to migrate through it.     

脑机接口：现状，问题与展望

本文综述现有脑机接口技术的最新发展,并讨论这些脑机接口技术的局限和存在的问题,如高估人类个体大脑的功能、对大脑信息存储方式缺乏了解等.基于大脑信息存储的"二维码"模型,我们认为目前的脑机接口技术方案仅适用于一些简单的应用场景,如了解受测者的情绪变化、生命活动的状态,以及控制体外器械等,而无法通过脑机接口技术获取脑内诸如记忆与思考等信息的精准细节.我们也提出,向大脑输入信息的脑机接口技术有较大的发展空间,比如发展具有多种调控效果、物理和生化技术结合的深脑刺激装置,有可能广泛应用于抑郁症、癫痫等脑疾病的治疗,以及应用于短期脑力的增强.本文对于目前的脑机接口研究领域具有一定的警示和启发意义.