• 【在创伤性脑损伤的小鼠模型中,远程缺血条件保留了认知和运动协调。】 复制标题 收藏 收藏
    DOI:10.1097/TA.0000000000001626 复制DOI
    作者列表:Sandweiss AJ,Azim A,Ibraheem K,Largent-Milnes TM,Rhee P,Vanderah TW,Joseph B
    BACKGROUND & AIMS: INTRODUCTION:Management of traumatic brain injury (TBI) is focused on minimizing or preventing secondary brain injury. Remote ischemic conditioning (RIC) is an established treatment modality that has been shown to improve patient outcomes in different clinical settings by influencing inflammatory insults. In a clinical trial, RIC showed amelioration of SB100 and neuron-specific enolase. The aim of our study was to further elucidate the mechanisms and outcome when applying RIC in a mouse model of traumatic brain injury. METHODS:We subjected 100 male C57BL mice to a closed-skull cortical-controlled impact injury. Two hours after the TBI, the animals were allocated to either the RIC group (n = 50) or the sham group (n = 50). By clamping the exposed femoral artery, we induced RIC by six 4-minute cycles of ischemia and reperfusion. Circulating levels of S100-B, neuron-specific enolase, and glial fibrillary acidic protein were measured at multiple time points. Animals were additionally observed daily for cognition and motor coordination via novel object recognition and rotarod. Brain sections were stained and evaluated for neuronal injury at post-TBI Day 5. RESULTS:The RIC animals had a significantly higher recognition index than did sham at 24, 48, and 72 hours after intervention. Rotarod latency was higher in the RIC animals compared to the sham animals at all-time points, and statistically significant at 120 hours after intervention. The RIC group demonstrated preserved cognitive function and motor coordination compared to the sham. On hematoxylin and eosin and immunohistochemical staining of brain sections, there was less area of neuronal degeneration and astrocytosis, respectively, in the RIC group compared to the sham group. There was no significant difference in systemic neuronal markers between the RIC and sham animals. CONCLUSION:Remote ischemic conditioning 2 hours after injury preserved cognitive functions and motor coordination in a mouse model of TBI. Remote ischemic conditioning can preserve viability of neurons and astrocytes after TBI and has potential as a clinically noninvasive and relatively easy method to improve outcome after TBI. LEVEL OF EVIDENCE:Therapeutic studies, randomized controlled trial, level I.
    背景与目标:
  • 【静息心率预测缺血性卒中后早期抑郁和认知: 一项初步研究。】 复制标题 收藏 收藏
    DOI:10.1016/j.jstrokecerebrovasdis.2017.05.040 复制DOI
    作者列表:Tessier A,Sibon I,Poli M,Audiffren M,Allard M,Pfeuty M
    BACKGROUND & AIMS: BACKGROUND:Early detection of poststroke depression (PSD) and cognitive impairment (PSCI) remains challenging. It is well documented that the function of autonomic nervous system is associated with depression and cognition. However, their relationship has never been investigated in the early poststroke phase. This pilot study aimed at determining whether resting heart rate (HR) parameters measured in early poststroke phase (1) are associated with early-phase measures of depression and cognition and (2) could be used as new tools for early objective prediction of PSD or PSCI, which could be applicable to patients unable to answer usual questionnaires. METHODS:Fifty-four patients with first-ever ischemic stroke, without cardiac arrhythmia, were assessed for resting HR and heart rate variability (HRV) within the first week after stroke and for depression and cognition during the first week and at 3 months after stroke. RESULTS:Multiple regression analyses controlled for age, gender, and stroke severity revealed that higher HR, lower HRV, and higher sympathovagal balance (low-frequency/high-frequency ratio of HRV) were associated with higher severity of depressive symptoms within the first week after stroke. Furthermore, higher sympathovagal balance in early phase predicted higher severity of depressive symptoms at the 3-month follow-up, whereas higher HR and lower HRV in early phase predicted lower global cognitive functioning at the 3-month follow-up. CONCLUSIONS:Resting HR measurements obtained in early poststroke phase could serve as an objective tool, applicable to patients unable to complete questionnaires, to help in the early prediction of PSD and PSCI.
    背景与目标:
  • 【超越人类岛叶皮层的三方认知-情感-感受模型。】 复制标题 收藏 收藏
    DOI:10.1162/jocn_a_00462 复制DOI
    作者列表:Uddin LQ,Kinnison J,Pessoa L,Anderson ML
    BACKGROUND & AIMS: :Functional MRI studies report insular activations across a wide range of tasks involving affective, sensory, and motor processing, but also during tasks of high-level perception, attention, and control. Although insular cortical activations are often reported in the literature, the diverse functional roles of this region are still not well understood. We used a meta-analytic approach to analyze the coactivation profiles of insular subdivisions-dorsal anterior, ventral anterior, and posterior insula-across fMRI studies in terms of multiple task domains including emotion, memory, attention, and reasoning. We found extensive coactivation of each insular subdivision, with substantial overlap between coactivation partners for each subdivision. Functional fingerprint analyses revealed that all subdivisions cooperated with a functionally diverse set of regions. Graph-theoretical analyses revealed that the dorsal anterior insula was a highly "central" structure in the coactivation network. Furthermore, analysis of the studies that activate the insular cortex itself showed that the right dorsal anterior insula was a particularly "diverse" structure in that it was likely to be active across multiple task domains. These results highlight the nuanced functional profiles of insular subdivisions and are consistent with recent work suggesting that the dorsal anterior insula can be considered a critical functional hub in the human brain.
    背景与目标: : 功能性MRI研究报告了涉及情感,感觉和运动处理的广泛任务中的岛状激活,以及在高级感知,注意力和控制任务中的岛状激活。尽管文献中经常报道岛状皮层激活,但该区域的各种功能作用仍未得到很好的理解。我们使用荟萃分析方法分析了跨fMRI研究的岛状细分的共激活谱,包括情感,记忆,注意力和推理等多个任务域,包括背前,腹前和后岛状。我们发现每个岛状细分的共同激活广泛,每个细分的共同激活伙伴之间存在大量重叠。功能指纹分析表明,所有分区都与功能上不同的区域集合作。图理论分析表明,背前岛是共激活网络中的高度 “中心” 结构。此外,对激活岛叶皮层本身的研究的分析表明,右背前岛是一种特别 “多样化” 的结构,因为它可能在多个任务域中活跃。这些结果突显了岛状分区的细微功能特征,并且与最近的工作相一致,这表明背前岛可以被认为是人脑中的关键功能中枢。
  • 【脑血管病和淀粉样 β 负荷对皮质下血管性认知障碍受试者认知的影响。】 复制标题 收藏 收藏
    DOI:10.1016/j.neurobiolaging.2013.06.026 复制DOI
    作者列表:Park JH,Seo SW,Kim C,Kim SH,Kim GH,Kim ST,Jeon S,Lee JM,Oh SJ,Kim JS,Choe YS,Lee KH,Shin JS,Kim CH,Noh Y,Cho H,Yoon CW,Kim HJ,Ye BS,Ewers M,Weiner MW,Lee JH,Werring DJ,Na DL
    BACKGROUND & AIMS: :Cerebrovascular disease (CVD) and amyloid burden are the most frequent pathologies in subjects with cognitive impairment. However, the relationship between CVD, amyloid burden, and cognition are largely unknown. We aimed to evaluate whether CVD (lacunes, white matter hyperintensities, and microbleeds) and amyloid burden (Pittsburgh compound B [PiB] retention ratio) contribute to cognitive impairment independently or interactively. We recruited 136 patients with subcortical vascular cognitive impairment who underwent magnetic resonance imaging, PiB-positron emission tomography, and neuropsychological testing. The number of lacunes was associated with memory, frontal dysfunctions, and disease severity. The volume of white matter hyperintensities and the PiB retention ratio were associated only with memory dysfunction. There was no direct correlation between CVD markers and PiB retention ratio except that the number of lacunes was negatively correlated with the PiB retention ratio. In addition, there were no interactive effects of CVD and PiB retention ratio on cognition. Our findings suggest that CVD and amyloid burden contribute independently and not interactively to specific patterns of cognitive dysfunction in patients with subcortical vascular cognitive impairment.
    背景与目标: : 脑血管疾病 (CVD) 和淀粉样蛋白负担是认知障碍患者最常见的病理。然而,CVD,淀粉样蛋白负担和认知之间的关系在很大程度上尚不清楚。我们旨在评估CVD (腔隙,白质高信号和微出血) 和淀粉样蛋白负荷 (匹兹堡化合物B [PiB] 保留比) 是否独立或交互地导致认知障碍。我们招募了136名皮质下血管性认知障碍患者,他们接受了磁共振成像,PiB-正电子发射断层扫描和神经心理学测试。腔隙的数量与记忆,额叶功能障碍和疾病严重程度有关。白质高信号的体积和PiB保留率仅与记忆功能障碍有关。CVD标记与PiB保留率之间没有直接相关性,只是腔隙数与PiB保留率呈负相关。此外,CVD和PiB保留率对认知没有交互作用。我们的发现表明,在皮质下血管性认知障碍患者中,CVD和淀粉样蛋白负担独立且非交互作用地促进了认知功能障碍的特定模式。
  • 【认知功能的快照: 在现实世界的住院环境中,为精神分裂症和其他慢性精神疾病提供有效评估认知的工具。】 复制标题 收藏 收藏
    DOI:10.1016/j.psychres.2013.07.006 复制DOI
    作者列表:Wong QJ,Miller M,Fiorito A,Ireland J
    BACKGROUND & AIMS: :Previous research has led to the development of short batteries of tests that efficiently measure the cognitive functioning of individuals with schizophrenia. To attempt to replicate previous findings, we applied an empirical test selection strategy to archival cognitive test data of two non-overlapping inpatient samples of individuals with schizophrenia or schizoaffective disorder (total N=110). We then extended previous findings by applying the empirical test selection strategy to the archival data of two non-overlapping inpatient samples of individuals with various psychiatric disorders (total N=149). For each sample, tests were selected by examining the relationships between individual test scores and averaged test scores representing global cognitive functioning while taking into account test administration times. Across patient samples, digit symbol coding tasks, verbal fluency tasks, and tests with a processing speed component (Trail Making Test Part A and Stroop) emerged as efficient and effective indicators of overall cognitive functioning. A brief cognitive assessment tool incorporating coding, fluency, and processing speed tasks would provide a valid and clinically useful snapshot of a patient's level of cognitive functioning if more comprehensive testing cannot be completed.
    背景与目标: : 先前的研究导致了短电池测试的发展,可以有效地测量精神分裂症患者的认知功能。为了尝试复制先前的发现,我们将经验测试选择策略应用于精神分裂症或分裂情感障碍患者的两个非重叠住院患者样本的存档认知测试数据 (总计N = 110)。然后,我们通过将经验测试选择策略应用于两个非重叠的住院患者样本的档案数据来扩展先前的发现。患有各种精神疾病的个体 (总计N = 149)。对于每个样本,通过检查单个测试分数与代表整体认知功能的平均测试分数之间的关系来选择测试,同时考虑测试给药时间。在患者样本中,数字符号编码任务,言语流利度任务以及具有处理速度分量的测试 (跟踪测试a部分和Stroop) 成为整体认知功能的有效指标。如果无法完成更全面的测试,则包含编码,流利度和处理速度任务的简短认知评估工具将为患者的认知功能水平提供有效且临床有用的快照。
  • 【学龄前癫痫儿童的言语、语言和认知。】 复制标题 收藏 收藏
    DOI:10.1111/j.1469-8749.2008.02060.x 复制DOI
    作者列表:Selassie GR,Viggedal G,Olsson I,Jennische M
    BACKGROUND & AIMS: :We studied expressive and receptive language, oral motor ability, attention, memory, and intelligence in 20 6-year-old children with epilepsy (14 females, six males; mean age 6y 5mo, range 6y-6y 11mo) without learning disability, cerebral palsy (CP), and/or autism, and in 30 reference children without epilepsy (18 females, 12 males; mean age 6y 5mo, range 6y-6y 11mo). Ten children had partial, six primarily generalized, and four unclassified epilepsy. Fourteen were having monotherapy and six were taking two or more antiepileptic drugs; 13 children were free from seizures 3 months before the assessment. Results show no statistically significant difference between the groups concerning Verbal IQ, expressive and receptive grammar, and receptive vocabulary. The children with epilepsy had a significantly lower Performance IQ and lower scores in tests of oral motor ability, articulation, emerging literacy, auditory attention, short-term memory, and rapid word retrieval. Parent ratings revealed no significant difference in communicative ability. Polytherapy and early onset of epilepsy influenced some results. Preschool children with epilepsy without learning disability, CP, and/or autism may have receptive verbal ability within the normal range but visuoperceptual, auditory attentional, and speech-language difficulties that could affect school achievement. Careful testing of children with epilepsy who appear to be functioning within the normal range is needed because this may reveal specific impairments that require appropriate professional input.
    背景与目标: : 我们研究了20名6岁癫痫儿童 (14名女性,6名男性; 平均年龄6y 5mo,范围6y-6y 11mo) 的表达和接受语言,口腔运动能力,注意力,记忆力和智力,无学习障碍,脑瘫 (CP) 和/或自闭症,在30例无癫痫的参考儿童中 (女性18例,男性12例; 平均年龄6y 5mo,范围6y-6y 11mo)。10名儿童患有部分癫痫,6名主要是全身性癫痫和4名未分类癫痫。14例接受单药治疗,6例服用两种或多种抗癫痫药物; 13名儿童在评估前3个月没有癫痫发作。结果显示,在言语智商,表达和接受语法以及接受词汇方面,两组之间没有统计学上的显着差异。癫痫患儿的智商明显较低,在口腔运动能力,清晰度,新兴识字能力,听觉注意力,短期记忆和快速单词检索方面的得分较低。父母评分显示沟通能力没有显着差异。多治疗和癫痫的早期发作影响了一些结果。没有学习障碍,CP和/或自闭症的患有癫痫的学龄前儿童的言语能力可能在正常范围内,但视觉,听觉注意和言语障碍可能会影响学业成绩。需要对似乎在正常范围内起作用的癫痫儿童进行仔细测试,因为这可能会发现需要适当专业投入的特定损伤。
  • 【临床推理的综合模型: 认知和元认知的双过程理论。】 复制标题 收藏 收藏
    DOI:10.1111/j.1365-2753.2012.01900.x 复制DOI
    作者列表:Marcum JA
    BACKGROUND & AIMS: RATIONALE AND AIM:Clinical reasoning is an important component for providing quality medical care. The aim of the present paper is to develop a model of clinical reasoning that integrates both the non-analytic and analytic processes of cognition, along with metacognition. METHOD:The dual-process theory of cognition (system 1 non-analytic and system 2 analytic processes) and the metacognition theory are used to develop an integrated model of clinical reasoning. RESULTS:In the proposed model, clinical reasoning begins with system 1 processes in which the clinician assesses a patient's presenting symptoms, as well as other clinical evidence, to arrive at a differential diagnosis. Additional clinical evidence, if necessary, is acquired and analysed utilizing system 2 processes to assess the differential diagnosis, until a clinical decision is made diagnosing the patient's illness and then how best to proceed therapeutically. Importantly, the outcome of these processes feeds back, in terms of metacognition's monitoring function, either to reinforce or to alter cognitive processes, which, in turn, enhances synergistically the clinician's ability to reason quickly and accurately in future consultations. CONCLUSIONS:The proposed integrated model has distinct advantages over other models proposed in the literature for explicating clinical reasoning. Moreover, it has important implications for addressing the paradoxical relationship between experience and expertise, as well as for designing a curriculum to teach clinical reasoning skills.
    背景与目标:
  • 【茴拉西坦认知增强药对酪氨酸和l-色氨酸的荧光猝灭的荧光荧光研究: 使用Stern-Volmer和双对数图的猝灭机理。】 复制标题 收藏 收藏
    DOI:10.1002/bio.3778 复制DOI
    作者列表:Hassan SAE,Ahmed SAE,Helmy AH,Youssef NF
    BACKGROUND & AIMS: :A novel approach on fluorescence quenching of tyrosine and l-tryptophan is presented for spectrofluorimetric determination of aniracetam in drug substances and products. The quenching mechanism was investigated using Stern-Volmer plots and ultraviolet spectra figures of quencher-fluorophore mixtures. Binding constant and stoichiometry were calculated using double-log plots. The spectrofluorimetric method was optimized for the experimental conditions affecting fluorescence quenching including fluorophore concentration, diluent, and reaction time. Moreover, the pH-rate profile of aniracetam was studied using simple kinetics and found to be stable within the pH range 5-8. Fluorescence quenching of tyrosine and l-tryptophan were observed on addition of aniracetam in aqueous medium at pH 5.5-6.5. Aniracetam quenched the fluorescence of tyrosine and l-tryptophan in the concentration range 1-20 μg/ml and 0.3-20 μg/ml, respectively, with binomial relationships between quenching values (ΔF) and aniracetam concentration. Limits of detection were found to be 0.10 μg/ml for tyrosine-aniracetam and 0.14 μg/ml for l-tryptophan-aniracetam. Method validation was performed as per ICH guidelines and demonstrated that the developed spectrofluorimetric method was accurate, precise, specific, and suitable for analysis of aniracetam in routine quality control laboratories. All experimental materials and solvents used are eco-friendly, indicating that the cited spectrofluorimetric procedure is an excellent green method.
    背景与目标: : 提出了一种用于酪氨酸和l-色氨酸荧光猝灭的新方法,用于分光光度法测定药物和产品中的阿尼西坦。使用Stern-Volmer图和猝灭剂-荧光团混合物的紫外光谱图研究了猝灭机理。使用双对数图计算结合常数和化学计量。针对影响荧光猝灭的实验条件 (包括荧光团浓度,稀释剂和反应时间) 进行了优化。此外,使用简单的动力学研究了阿尼西坦的pH速率分布,发现在5-8的pH范围内稳定。在pH 5.5-6.5的水介质中加入茴拉西坦后,观察到酪氨酸和l-色氨酸的荧光猝灭。茴拉西坦分别在1-20μg/ml和0.3-20 μ g/ml的浓度范围内猝灭酪氨酸和l-色氨酸的荧光,猝灭值 (Δ f) 与茴拉西坦浓度之间具有二项式关系。发现酪氨酸-茴拉西坦的检出限为0.10 μ g/ml,l-色氨酸-茴拉西坦的检出限为0.14 μ g/ml。方法验证根据ICH指南进行,并证明所开发的荧光光谱法是准确,精确,特异性的,并且适用于常规质量控制实验室中的阿尼西坦分析。使用的所有实验材料和溶剂都是环保的,这表明所引用的荧光光谱法是一种出色的绿色方法。
  • 9 The native language of social cognition. 复制标题 收藏 收藏

    【社会认知的母语。】 复制标题 收藏 收藏
    DOI:10.1073/pnas.0705345104 复制DOI
    作者列表:Kinzler KD,Dupoux E,Spelke ES
    BACKGROUND & AIMS: :What leads humans to divide the social world into groups, preferring their own group and disfavoring others? Experiments with infants and young children suggest these tendencies are based on predispositions that emerge early in life and depend, in part, on natural language. Young infants prefer to look at a person who previously spoke their native language. Older infants preferentially accept toys from native-language speakers, and preschool children preferentially select native-language speakers as friends. Variations in accent are sufficient to evoke these social preferences, which are observed in infants before they produce or comprehend speech and are exhibited by children even when they comprehend the foreign-accented speech. Early-developing preferences for native-language speakers may serve as a foundation for later-developing preferences and conflicts among social groups.
    背景与目标: : 是什么导致人类将社会世界划分为群体,偏爱自己的群体而不利于他人?对婴儿和幼儿的实验表明,这些趋势是基于生命早期出现的倾向,部分依赖于自然语言。年幼的婴儿更喜欢看以前说母语的人。年龄较大的婴儿优先接受母语人士的玩具,学龄前儿童优先选择母语人士作为朋友。口音的变化足以唤起这些社会偏好,这些偏好是在婴儿产生或理解语音之前观察到的,即使他们理解了外来口音的语音,儿童也会表现出这种偏好。早期发展对母语人士的偏好可能是后来发展的偏好和社会群体之间冲突的基础。
  • 【成人认知的生物学相关性: 美国的中年 (MIDUS)。】 复制标题 收藏 收藏
    DOI:10.1016/j.neurobiolaging.2013.07.028 复制DOI
    作者列表:Karlamangla AS,Miller-Martinez D,Lachman ME,Tun PA,Koretz BK,Seeman TE
    BACKGROUND & AIMS: :Multiple biological processes are related to cognitive impairment in older adults, but their combined impact on cognition in midlife is not known. Using an array of measurements across key regulatory physiological systems and a state-of-the-art cognition battery that is sensitive to early changes, in a large, national sample of middle-aged and older adults, we examined the associations of individual biological systems and a combined, multi-system index, allostatic load, with cognitive performance. Allostatic load was strongly inversely associated with performance in both episodic memory and executive function. Of 7 biological systems, only the cardiovascular system was associated inversely with both; inflammation was associated inversely with episodic memory only, and glucose metabolism with executive function only. The associations of allostatic load with cognition were not different by age, suggesting that the implications of high allostatic load on cognitive functioning are not restricted to older adults. Findings suggest that a multi-system score, like allostatic load, may assist in the early identification of adults at increased risk for cognitive impairment.
    背景与目标: : 多种生物学过程与老年人的认知障碍有关,但尚不清楚它们对中年认知的综合影响。使用一系列关键调节生理系统的测量和对早期变化敏感的最先进的认知电池,在一个大型的,中老年人的国家样本中,我们检查了个体生物系统和组合的多系统指数的关联,静态负荷,具有认知性能。静态负荷与情景记忆和执行功能的性能呈负相关。在7个生物系统中,只有心血管系统与两者成反比; 炎症仅与情节记忆成反比,而葡萄糖代谢仅与执行功能成反比。异种负荷与认知的关联在年龄上没有差异,这表明高异种负荷对认知功能的影响不仅限于老年人。研究结果表明,多系统评分 (如同种异体负荷) 可能有助于早期识别认知障碍风险增加的成年人。
  • 【前额叶神经元向顶叶神经元传递信号,反映认知的执行控制。】 复制标题 收藏 收藏
    DOI:10.1038/nn.3509 复制DOI
    作者列表:Crowe DA,Goodwin SJ,Blackman RK,Sakellaridi S,Sponheim SR,MacDonald AW 3rd,Chafee MV
    BACKGROUND & AIMS: :Prefrontal cortex influences behavior largely through its connections with other association cortices; however, the nature of the information conveyed by prefrontal output signals and what effect these signals have on computations performed by target structures is largely unknown. To address these questions, we simultaneously recorded the activity of neurons in prefrontal and posterior parietal cortices of monkeys performing a rule-based spatial categorization task. Parietal cortex receives direct prefrontal input, and parietal neurons, like their prefrontal counterparts, exhibit signals that reflect rule-based cognitive processing in this task. By analyzing rapid fluctuations in the cognitive information encoded by activity in the two areas, we obtained evidence that signals reflecting rule-dependent categories were selectively transmitted in a top-down direction from prefrontal to parietal neurons, suggesting that prefrontal output is important for the executive control of distributed cognitive processing.
    背景与目标: : 前额叶皮层主要通过与其他关联皮层的连接来影响行为; 但是,前额叶输出信号传达的信息的性质以及这些信号对目标结构执行的计算有何影响在很大程度上是未知的。为了解决这些问题,我们同时记录了执行基于规则的空间分类任务的猴子的前额叶和后顶叶皮层中神经元的活动。顶叶皮层接收直接的前额叶输入,并且顶叶神经元像前额叶神经元一样,在此任务中表现出反映基于规则的认知处理的信号。通过分析这两个区域活动编码的认知信息的快速波动,我们获得了反映规则依赖类别的信号从前额叶神经元到顶叶神经元有选择地沿自上而下的方向传输的证据,这表明前额叶输出对于分布式认知处理的执行控制很重要。
  • 【来自间充质干细胞的外泌体2 ',3'-CNP促进海马CA1神经发生/神经发生,并有助于挽救受损大脑的认知/学习缺陷。】 复制标题 收藏 收藏
    DOI:10.1002/sctm.19-0174 复制DOI
    作者列表:Chen SY,Lin MC,Tsai JS,He PL,Luo WT,Chiu IM,Herschman HR,Li HJ
    BACKGROUND & AIMS: :Mesenchymal stem cells (MSCs) have been used in clinical studies to treat neurological diseases and damage. However, implanted MSCs do not achieve their regenerative effects by differentiating into and replacing neural cells. Instead, MSC secretome components mediate the regenerative effects of MSCs. MSC-derived extracellular vesicles (EVs)/exosomes carry cargo responsible for rescuing brain damage. We previously showed that EP4 antagonist-induced MSC EVs/exosomes have enhanced regenerative potential to rescue hippocampal damage, compared with EVs/exosomes from untreated MSCs. Here we show that EP4 antagonist-induced MSC EVs/exosomes promote neurosphere formation in vitro and increase neurogenesis and neuritogenesis in damaged hippocampi; basal MSC EVs/exosomes do not contribute to these regenerative effects. 2',3'-Cyclic nucleotide 3'-phosphodiesterase (CNP) levels in EP4 antagonist-induced MSC EVs/exosomes are 20-fold higher than CNP levels in basal MSC EVs/exosomes. Decreasing elevated exosomal CNP levels in EP4 antagonist-induced MSC EVs/exosomes reduced the efficacy of these EVs/exosomes in promoting β3-tubulin polymerization and in converting toxic 2',3'-cAMP into neuroprotective adenosine. CNP-depleted EP4 antagonist-induced MSC EVs/exosomes lost the ability to promote neurogenesis and neuritogenesis in damaged hippocampi. Systemic administration of EV/exosomes from EP4 -antagonist derived MSC EVs/exosomes repaired cognition, learning, and memory deficiencies in mice caused by hippocampal damage. In contrast, CNP-depleted EP4 antagonist-induced MSC EVs/exosomes failed to repair this damage. Exosomal CNP contributes to the ability of EP4 antagonist-elicited MSC EVs/exosomes to promote neurogenesis and neuritogenesis in damaged hippocampi and recovery of cognition, memory, and learning. This experimental approach should be generally applicable to identifying the role of EV/exosomal components in eliciting a variety of biological responses.
    背景与目标: : 间充质干细胞 (MSCs) 已被用于治疗神经系统疾病和损伤的临床研究。然而,植入的MSCs不能通过分化和替代神经细胞来实现其再生效果。相反,MSC分泌组成分介导了MSC的再生效应。MSC衍生的细胞外囊泡 (EVs)/外泌体携带负责抢救脑损伤的货物。我们先前表明,与未经治疗的MSCs/exosomes相比,EP4拮抗剂诱导的MSC EVs/exosomes具有增强的再生潜力来挽救海马损伤。在这里,我们显示EP4拮抗剂诱导的MSC EVs/外泌体在体外促进神经球形成,并增加受损海马的神经发生和神经发生; 基础MSC EVs/外泌体对这些再生作用没有贡献。EP4拮抗剂诱导的MSC EVs/外泌体中的2 ',3'-环核苷酸3 '-磷酸二酯酶 (CNP) 水平比基础MSC EVs/外泌体中的CNP水平高20倍。降低EP4拮抗剂诱导的MSC EVs/exosome中的exosome CNP水平升高会降低这些EVs/exosome在促进 β3-微管蛋白聚合和将有毒的2 ',3'-cAMP转化为神经保护性腺苷方面的功效。CNP耗尽的EP4拮抗剂诱导的MSC EVs/外泌体失去了促进受损海马神经发生和神经发生的能力。从EP4拮抗剂衍生的MSC EVs/exosomes全身施用EV/exosomes可修复由海马损伤引起的小鼠的认知,学习和记忆缺陷。相反,CNP耗尽的EP4拮抗剂诱导的MSC EVs/外泌体无法修复这种损伤。外泌体CNP有助于EP4拮抗剂引发的MSC EVs/外泌体促进受损海马神经发生和神经发生以及认知,记忆和学习恢复的能力。这种实验方法通常应适用于确定EV/外源体成分在引起各种生物学反应中的作用。
  • 【下丘脑-垂体肿瘤患者的社会认知。】 复制标题 收藏 收藏
    DOI:10.3389/fonc.2020.01014 复制DOI
    作者列表:Özyurt J,Mehren A,Boekhoff S,Müller HL,Thiel CM
    BACKGROUND & AIMS: :Objectives: The current study aimed to investigate whether childhood-onset craniopharyngioma patients are impaired in social-cognitive skills, and whether individual differences in task performance are modulated by the neurohormone oxytocin. Study design: We tested 31 adamantinomatous craniopharyngioma patients with and without hypothalamic lesions and 35 age- and gender-matched healthy controls. To test for between-group differences in social-cognitive skills, we experimentally assessed participants' abilities to interpret social signs or dispositions and to understand others' thoughts, feelings, and intentions. Associations between fasting oxytocin saliva concentrations and task performance were analyzed across the whole group of participants. Results: Compared to controls, patients with hypothalamic lesions were significantly less able to identify the correct emotional content of vocal expressions and to understand others' mental states. Judgements of trustworthiness were not different between patients and controls. There were no correlations between the primary measures of task performance and fasting oxytocin saliva concentrations. Conclusions: This is the first study to show that craniopharyngioma patients with hypothalamic lesions are impaired in some aspects of social cognition, which are of high relevance for everyday social interactions. These deficits suggest a disruption of the normal functionality of hypothalamic-fronto-limbic networks and/or additional areas of the social brain, which are at particular risk by hypothalamic location of the tumor and its treatment.
    背景与目标: : 目的: 本研究旨在调查儿童发病的颅咽管瘤患者的社交认知能力是否受损,以及神经激素催产素是否调节了任务表现的个体差异。研究设计: 我们测试了31例有和没有下丘脑病变的金刚烷瘤性颅咽管瘤患者以及35例年龄和性别相匹配的健康对照。为了测试社交认知技能的组间差异,我们通过实验评估了参与者解释社交标志或性格以及理解他人的想法,感受和意图的能力。在整个参与者组中分析了空腹催产素唾液浓度与任务表现之间的关联。结果: 与对照组相比,下丘脑病变患者识别声音表达的正确情绪内容和理解他人心理状态的能力明显降低。患者和对照组之间对可信度的判断没有差异。任务表现的主要指标与空腹催产素唾液浓度之间没有相关性。结论: 这是第一项表明患有下丘脑病变的颅咽管瘤患者在社交认知的某些方面受到损害的研究,这与日常社交互动具有很高的相关性。这些缺陷表明下丘脑-额边缘网络的正常功能和/或社交大脑的其他区域受到破坏,这些区域因下丘脑肿瘤的位置及其治疗而特别危险。
  • 【护士健康研究中的轮班工作和认知。】 复制标题 收藏 收藏
    DOI:10.1093/aje/kwt214 复制DOI
    作者列表:Devore EE,Grodstein F,Schernhammer ES
    BACKGROUND & AIMS: :Rotating night-shift work, which can disrupt circadian rhythm, may adversely affect long-term health. Experimental studies indicate that circadian rhythm disruption might specifically accelerate brain aging; thus, we prospectively examined shift-work history at midlife as associated with cognitive function among older women in the Nurses' Health Study. Women reported their history of rotating night-shift work in 1988 and participated in telephone-based cognitive interviews between 1995 and 2001; interviews included 6 cognitive tests that were subsequently repeated 3 times, at 2-year intervals. We focused on shift work through midlife (here, ages 58-68 years) because cognitive decline is thought to begin during this period. Using multivariable-adjusted linear regression, we evaluated mean differences in both "average cognitive status" at older age (averaging cognitive scores from all 4 interviews) and rates of cognitive decline over time across categories of shift-work duration at midlife (none, 1-9, 10-19, or ≥20 years). There was little association between shift work and average cognition in later life or between shift work and cognitive decline. Overall, this study does not clearly support the hypothesis that shift-work history in midlife has long-term effects on cognition in older adults.
    背景与目标: : 夜班工作会破坏昼夜节律,可能会对长期健康产生不利影响。实验研究表明,昼夜节律破坏可能会特别加速大脑衰老; 因此,我们在护士健康研究中前瞻性地研究了中年时的轮班工作史与老年妇女的认知功能有关。妇女报告了其夜班1988年的历史,并1995年和2001年参加了基于电话的认知访谈; 访谈包括6项认知测试,随后每隔2年重复3次。我们专注于中年 (这里是58-68岁) 的轮班工作,因为认知能力下降被认为是在此期间开始的。使用多变量调整线性回归,我们评估了老年人 “平均认知状态” (所有4次访谈的平均认知得分) 和中年轮班工作时间类别随时间推移认知下降的平均差异 (无,1-9,10-19,或 ≥ 20年)。轮班工作与以后生活中的平均认知之间或轮班工作与认知下降之间几乎没有关联。总的来说,这项研究没有明确支持这样的假设,即中年的轮班工作史对老年人的认知有长期影响。
  • 【大脑和认知的终生可塑性: 从问题到证据再到背部。】 复制标题 收藏 收藏
    DOI:10.1016/j.neubiorev.2013.10.003 复制DOI
    作者列表:Raz N,Lindenberger U
    BACKGROUND & AIMS: :Experience-related changes induced by modification of environment, physical exercise, or cognitive training affect brain structure and function. Research on brain plasticity and its relationship to experiential changes gathers momentum and attracts significant public interest. This collection of papers is based on presentation at the First International Conference on Life-Span Plasticity of Brain and Behavior: A Cognitive Neuroscience Perspective that took place in Detroit, MI, on October 12-14, 2011. The conference honored Margret M. and Paul B. Baltes, the pioneers of life-span developmental psychology who initiated some of the first studies on experience- and training-related changes in cognition across the life span.
    背景与目标: : 环境改变,体育锻炼或认知训练引起的与经验相关的变化会影响大脑的结构和功能。大脑可塑性及其与经验变化的关系的研究聚集了动力,并引起了公众的极大兴趣。这些论文集基于在密歇根州底特律举行的第一届关于大脑和行为的寿命可塑性国际会议上的演讲: 认知神经科学的观点2011年10月12至14日。会议表彰了终身发展心理学的先驱Margret M.和Paul B. Baltes,他们发起了一些有关终生与经验和培训相关的认知变化的首批研究。

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