胆囊收缩素对脂多糖诱发的病态行为及外周细胞因子的影响

细胞因子在病态行为的产生中有重要的作用。八肽胆囊收缩素在前人研究中表明能够拮抗脂多糖在大鼠体内引起的细胞因子的分泌。实验目的：利用八肽胆囊收缩素的抗炎作用研究细胞因子在病态行为中的作用。实验方法：共分两个实验进行, 将大鼠分为控制组、免疫激活剂脂多糖组(200 μg/kg剂量, 腹腔注射)以及注射不同剂量的八肽胆囊收缩素的实验组(分别为20 μg/kg 、40 μg/kg 、80 μg/kg 和120 μg/kg剂量), 各实验组在注射脂多糖前半小时注射相应剂量的八肽胆囊收缩素, 药物注射两小时后进行行为实验 (糖水摄取量测验、旷场测验和高架十字迷宫测验), 然后对大鼠前炎性细胞因子包括白细胞介素-1β(IL-1β)、白细胞介素-6 (IL-6)、肿瘤坏死因子-α (TNF-α)及抗炎性细胞因子白细胞介素-10(IL-10)的血清浓度进行分析。实验结果：脂多糖诱发大鼠产生病态行为, 与控制组相比, 脂多糖组糖水摄取量降低, 旷场测验中活动性降低, 高架闭臂进入次数减少; 脂多糖诱导炎性细胞因子分泌增加, 与控制组相比, 脂多糖组前炎性细胞因子IL-1β、IL-6、TNF-α的分泌增加。在脂多糖注射前注射八肽胆囊收缩素能够抑制前炎性细胞因子IL-1β、IL-6、TNF-α的分泌, 但八肽胆囊收缩素未能改善免疫诱导的病态行为。结论：本实验结果表明仅改变外周的细胞因子浓度并不能完全改变动物的病态行为, 病态行为的产生可能与脑区的细胞因子有更大的联系。     

国外精神病态罪犯的脑机制研究述评

精神病态是一种个体表现在人际关系、情感、生活方式和反社会特质等方面的人格障碍, 与非精神病态者相比, 精神病态者更容易违反社会规则和法律, 表现出更加残忍和极端的侵犯模式, 犯罪的起始年龄更早, 犯罪活动更为广泛和多样, 累犯率非常高。国外关于精神病态罪犯脑机制的ERP研究表明精神病态罪犯注意朝向、语义和情感加工以及对错误加工的后期阶段存在缺陷。MRI和fMRI的研究表明, 大脑结构异常以及额叶-边缘系统回路活动异常与精神病态行为有关。     

大脑慢电活动研究及其进展

目前对脑电活动的研究大多局限于频率在０．５－４０Ｈｚ的活动范围内,其研究方法无明显改进,对大脑慢电活动的研究尚未受到应有的重视．对脑慢电活动的记录有两大类方法：复杂直流放大技术和脑涨落图技术．脑涨落图技术能对大脑慢电活动进行精确的定量分析,巳找出其在各种生理和病理状态下的时空精细结构,并初步揭示出慢电活动与神经化学振荡的关系,因而为在无损条件下从宏观整合角度研究大脑的复杂功能状态及其生理生化基础提供了一种有效可行的方法．     

细胞因子和抑郁症

在心理神经免疫学领域,越来越多的证据表明神经和免疫之间存在双向交流通路,免疫系统可能在一些心理精神障碍中具有重要作用。“抑郁症的细胞因子假说”认为细胞因子作为神经调质,可能在抑郁症的病因和病理过程中具有重要作用。这个假说得到了很多证据的支持。而在动物身上应用前炎性细胞因子也能够引起与人类抑郁症行为症状非常类似的“病态行为”。研究认为外周细胞因子通过信号传导进入脑内与中枢产生的细胞因子共同作用于下丘脑－垂体－肾上腺轴和5－羟色胺系统,从而导致抑郁症。细胞因子的中枢效应可以解释很多抑郁症状,“抑郁症的细胞因子假说”为探讨抑郁症状的机制和治疗抑郁症提供了一个新的视角     

高焦虑个体对负性情绪信息的注意移除发生困难

本研究目的是探讨高焦虑个体对负性情绪信息注意偏向的特点。采用了焦虑组-对照组设计和情绪stroop范式分离快效应和慢效应的方法。实验1发现,焦虑组有负性情绪信息干扰的快、慢效应,对照组只有快效应。实验2发现,词语负性情绪信息干扰的慢效应从该词之后第一个词开始,持续到第二个。焦虑组对负性情绪信息的注意移除发生困难,可能是焦虑情绪延续的原因,同时为焦虑情绪的干预提供依据。。     

知觉与行为的分离在视错觉研究中的验证

知觉与行为的分离是指人的视觉对物体的知觉与对行为的控制属于两个不同的系统。最早人们从临床病例中发现存在知觉与行为的分离,以后Aglioti等利用铁钦纳错觉实验证实正常人中也存在这一分离现象。一些研究者将两者的分离看作是两个不同视觉皮层通路（腹侧知觉系统和背侧视觉运动系统）的结果。围绕这一分离现象的实验和假说引发了不少的争论。该文回顾了十年来利用错觉实验所做的众多验证性研究,分析了支持和否定分离现象存在的各类证据,对一些重要结果和观点进行了总结,并由此提出了自己的看法。     

文化差异视角下个体合作行为的产生、影响机制建构及认知神经基础

合作行为是指个体或群体之间为了实现共同的目标和利益而进行的协同行为或意向。本文基于行为-认知-大脑的三重映射关系,对合作行为的文化差异性进行了深入阐释,并在此基础上构建了文化影响合作行为的社会认知中介模型;未来研究可从实证视角对合作行为文化差异的社会认知内容、认知神经机制等方面进行验证、挖掘和改善。     

太极拳技能学习早期大脑功能的动态变化：基于运动表象的fMRI研究

为了解太极拳技能学习早期大脑功能的动态变化特点,本研究共招募29名太极拳零基础被试(19名实验组被试,10名对照组被试),采用多时点纵向追踪设计,借助于功能磁共振成像技术,采集技能学习早期不同时点被试完成运动表象任务时的行为和脑功能数据。结果发现：(1)太极拳技能学习早期,技能水平表现出先慢后快的变化特征,运动表象质量也具有变好的趋势;(2)随着太极拳技能水平的提高,运动表象任务诱发的左侧颞上回和左侧楔前叶的激活显著增强,且同样表现出先慢后快的变化特征;(3)相关检验发现,左侧颞上回和左侧楔前叶的激活与运动表象质量以及太极拳技能水平具有中等程度的相关。研究表明,太极拳技能学习早期,左侧颞上回和左侧楔前叶会伴随着太极拳技能水平的提高而发生改变,太极拳技能学习有助于优化与序列动作学习有关的脑区功能。     

做梦的人多健康长寿

人的睡眠分快波睡和慢波睡眠两个阶段,而梦一般发生在快波睡眠阶段。人在一夜的睡眠中,从无意识的沉睡进入奇妙的梦幻,一般有2-6次。在做梦的这个阶段,眼球在闭着的眼皮下转动,这个人脑虽说是相对的静的,其实它是处在活动状态的,这是可从脑电波中测出快速紊乱的电波,其强度有时竟能超过白天活动的强度。但脑内有一种神经中心,它的职能就是在人做梦时抑制肌肉活动,使梦中的行为不会超出精神范围而变成行为。     

内源性睡眠肽的探论

本世纪五十年代发现睡眠包括两种类型的事实业已得到公认。这两类睡眠是慢波睡眠(SWS)和快波睡眠(FWS),通常前者还可称作非快眼动睡眠(NREMS)或同步睡眠,后者还可称作快眼动睡眠(REMS)或异相睡眠(PS)。成年人的慢波睡眠又包括4个分期。慢波1期的EEG特点是α波降低并呈现若干θ波;慢波2期在θ活动的背景上呈现σ梭形波“K-复合体”波;慢波3和4期的特征是高振幅的δ波,差异是4期的δ波指数较3期更高。快波睡眠的EEG特征与觉醒时相似。两类睡眠是哺乳类普遍具有的特征。     

Subregion-specific dendritic spine abnormalities in the hippocampus of Fmr1 KO mice

Fragile X syndrome (FXS) is the most common inherited form of mental retardation and is caused by the lack of fragile X mental retardation protein (FMRP). In the brain, spine abnormalities have been reported in both patients with FXS and Fmr1 knockout mice. This altered spine morphology has been linked to disturbed synaptic transmission related to altered signaling in the excitatory metabotropic glutamate receptor 5 (mGluR5) pathway. We investigated hippocampal protrusion morphology in adult Fmr1 knockout mice. Our results show a hippocampal CA1-specific altered protrusion phenotype, which was absent in the CA3 region of the hippocampus. This suggests a subregion-specific function of FMRP in synaptic plasticity in the brain.     

Brain interleukin-1 is involved in spatial memory and passive avoidance conditioning

Within the brain, the inflammatory cytokine interleukin-1 (IL-1) mediates illness-associated neural, neuroendocrine, and behavioral responses; however, its role in normal neurobehavioral processes is not clear. To examine the role of IL-1 signaling in memory, we infused Long-Evans rats intracerebroventricularly with IL-1beta (10 ng/rat), IL-1 receptor antagonist (IL-1ra, 100 microg/rat), or saline immediately following a learning task and tested memory functioning 1-8 days later. In the Morris water maze (MWM), IL-1ra caused memory impairment in the hippocampus-dependent, spatial version, whereas IL-1beta had no effect. Neither IL-1beta nor IL-1ra influenced the hippocampus-independent, nonspatial version of the MWM. In the passive avoidance response, which also depends on hippocampal functioning, IL-1ra caused memory impairment, and IL-1beta caused memory improvement. These results suggest that IL-1 signaling within the hippocampus plays a critical role in learning and memory processes.     

Genetic approaches to understanding brain development: holoprosencephaly as a model

Holoprosencephaly (HPE) is the most common major developmental defect of the forebrain in humans. Clinical expression is variable, ranging from a small brain with a single cerebral ventricle and cyclopia to clinically unaffected carriers in familial HPE. Significant etiologic heterogeneity exists in HPE and includes both genetic and environmental causes. Defects in the cell signaling pathway involving the Sonic Hedgehog (SHH) gene, as well as defects in the cholesterol biosynthesis have been shown to cause HPE in humans. More recently, HPE genes from additional signaling pathways have been identified. These discoveries and current genetic approaches serve as a paradigm for studying normal and abnormal brain morphogenesis. MRDD Research Reviews 6:15-21, 2000.     

神经生长因子对大鼠脑缺血再灌注后TGF-β1和IL-1β表达的影响及临床意义

探讨神经生长因子（NGF）的脑保护作用及临床意义。采用大鼠脑缺血再灌注（MCAO）模型,选取健康成年SD大鼠55只,随机分为假手术组（n=5）、对照组（n=30）,NGF组（n=10）和生理盐水对照组（n=10）进行造模,应用免疫组化方法检测TGF-β1和IL-1β的表达。可见NGF组神经功能障碍明显减轻,TGF-β1...     

Neurophysiological preconditions of syntax acquisition

Although the neural network for language processing in the adult brain is well specified, the neural underpinning of language acquisition is still underdetermined. Here, we define the milestones of syntax acquisition and discuss the possible neurophysiological preconditions thereof. Early language learning seems to be based on the bilateral temporal cortices. Subsequent syntax acquisition apparently primarily recruits a neural network involving the left frontal cortex and the temporal cortex connected by a ventrally located fiber system. The late developing ability to comprehend syntactically complex sentences appears to require a neural network that connects Broca’s area to the left posterior temporal cortex via a dorsally located fiber pathway. Thus, acquisition of syntax requires the maturation of fiber bundles connecting the classical language-relevant brain regions.     

Neuroimmune stress responses: reciprocal connections between the hypothalamus and the brainstem

Hypothalamic nuclei, particularly the paraventricular nuclei (PVN), are important brain sites responsible for eliciting stress responses following a systemic immune challenge. The activation of PVN cells by a systemic immune challenge is critically dependent on the integrity of inputs from brainstem cells situated in the nucleus tractus solitarius (NTS) and ventrolateral medulla (VLM). Interestingly, a descending pathway from the PVN to the brainstem, recruited by systemic immune challenge, might also exist. It is well documented that PVN neurons innervate the NTS and VLM and recent evidence from our laboratory shows that lesions of the PVN reduce brainstem cell responses elicited by a systemic bolus of the proinflammatory cytokine interleukin-1beta (IL-1beta). Although a number of different PVN divisions are candidates for the source of inputs to the brainstem, we have demonstrated that the majority of descending PVN projections recruited by systemic IL-1beta arise from cell bodies localized in the medial and lateral parvocellular PVN. These findings suggest that central nervous system responses to an immune challenge are likely to involve complex reciprocal connections between the PVN and the brainstem, whereby brainstem cell populations could essentially act as integratory sites for descending and ascending immune signals. For instance, these brainstem pathways may have significant implications not only for the regulation of central hypothalamic and extra-hypothalamic targets but also the autonomic nervous system.     

Contribution of acetylcholine to visual cortex plasticity

Acetylcholine is involved in a variety of brain functions. In the visual cortex, the pattern of cholinergic innervation varies considerably across different mammalian species and across different cortical layers within the same species. The physiological effects of acetylcholine in the visual cortex display complex responses, which are likely due to cholinergic receptor subtype composition in cytoplasm membrane as well as interaction with other transmitter systems within the local neural circuitry. The functional role of acetylcholine in visual cortex is believed to improve the signal-to-noise ratio of cortical neurons during visual information processing. Available evidence suggests that acetylcholine is also involved in experience-dependent visual cortex plasticity. At the level of synaptic transmission, activation of muscarinic receptors has been shown to play a permissive role in visual cortex plasticity. Among the muscarinic receptor subtypes, the M(1) receptor seems to make a predominant contribution towards modifications of neural circuitry. The signal transduction cascade of the cholinergic pathway may act synergistically with that of the NMDA receptor pathway, whose activation is a prerequisite for cortical plasticity.     

神经颗粒素与脑老化、疾病及应激关系

神经颗粒素是一种神经元特异性、Ca2＋敏感性的鈣调蛋白（CaM）结合蛋白,是蛋白激酶C的突触后底物,与信号传导和长时程增强（LTP）有关。这是一种新发现的脑特异性蛋白质。主要分布在前脑和海马,在皮质、海马CA1-CA3区、齿状回、纹状体和杏仁核中高表达。在大脑发育的不同阶段,神经颗粒素在脑内的含量和分布区域会发生变化,其生物学作用受到国内外学者的关注。近年来国外学者开始对神经颗粒素与脑老化、疾病及应激关系进行考查。该文将着重介绍对神经颗粒素在脑老化、疾病和应激过程中所扮演的角色的研究工作及其新发现,目的是对脑与行为关系的理解及有关的脑机制的研究提供一个新的视点。     

Ursolic acid attenuates lipopolysaccharide-induced cognitive deficits in mouse brain through suppressing p38/NF-κB mediated inflammatory pathways

Evidence indicates that systemic administration of lipopolysaccharide (LPS) induces brain inflammation, ultimately resulting in cognitive deficits. Ursolic acid (UA), a plant-derived pentacyclic triterpenoid, is well known to possess multiple biological functions, including antioxidant, anti-tumor and anti-inflammatory activities. In the present study, we assessed the protective effect of UA against the LPS-induced cognitive deficits in mice. We found that UA significantly improved cognitive deficits of LPS-treated mice in open field, step-through passive avoidance and Morris water maze tasks. One potential mechanism of this action was attributed to the decreased production of pro-inflammatory markers including COX-2, iNOS, TNF-α, IL-1β, IL-2 and IL-6 in LPS-treated mouse brain. Mechanistically, UA markedly inhibited LPS-induced IκBα phosphorylation and degradation, NF-κB p65 nuclear translocation and p38 activation in mouse brain, but did not affect the activation of TLR4, MyD88, ERK, JNK and Akt. Taken together, these results suggest that UA may be useful for mitigating inflammation-associated brain disorders by inhibiting pro-inflammatory factors production, at least in part, through blocking the p38/NF-κB signaling pathways.     

Cytokine stress responses depend on lateralization in mice

In mice, lateralization as assessed by paw preference represents a behavioral trait linked to immune reactivity and stress susceptibility. Right-pawed mice are more reactive to stress than left-pawed animals when brain metabolism, activation of the corticoid axis, and depression of lymphoproliferation are studied. Since stress responses include cytokine production, we address the possibility that lateralization influences the production of cytokines--especially interleukin (IL)-1--responsible for depression of lymphoproliferation and activation of the corticoid axis. Increased plasma IL-1 level that may be considered as a stress marker, was observed in right- but not in left-pawed mice submitted to a 4 h-restraint. Likewise, plasma levels were greater in right- than in left-pawed animals 2 h after the administration of a low dose of lipopolysaccharides (LPS). By contrast, there was no lateralization effect in restraint-induced plasma level of IL-6 or in the LPS-induced increase in plasma IL-10. Prazosin, an alpha1/alpha2 adrenoreceptor antagonist, drastically increased plasma IL-10 induced by LPS, reduced plasma levels of IL-1 and abolished the effect of lateralization observed after LPS alone. This suggests that alpha-adrenergic modulation of IL-1 production depends on lateralization through mechanisms that need further investigation.