ACE与体外循环后心肌损伤的关系

观察体外循环后血管紧张素转换酶（ACE）及心肌标志物的变化,探讨ACE与心肌损伤之间的关系。20例择期CPB心脏手术患者分别于术前（T1）、CPB60rain（T2）、CPB后30min（T3）、4h（T4）、24h（T5）及48h（T6）各时间点测定静脉血中下列各指标的水平：ACE、肌钙蛋白I（cTnI）、肌红蛋白（...     

Purple sweet potato color repairs d-galactose-induced spatial learning and memory impairment by regulating the expression of synaptic proteins

Purple sweet potato color (PSPC), a class of naturally occurring anthocyanins used to color food (E163), has been reported to possess a variety of biological activities, including anti-oxidant, anti-tumor, and anti-inflammatory. The effect of PSPC on the spatial learning and memory of mice treated with d-galactose (d-gal) was evaluated by the Morris water maze; d-gal-treated mice had decreased performance compared with mice in the vehicle and PSPC groups, while the PSPC + d-gal group showed significantly shortened escape latency to platform, increased swimming speed, more target quadrant search time and more platform crossings as compared with the d-gal group. Brain functions, such as memory formation and recovery of function after injury, depend on proper regulation of the expression levels of the pre- and post-synaptic proteins. We investigated the expression of four pre-synaptic proteins (growth-associated protein-43, synapsin-I, synaptophysin, and synaptotagmin) and two post-synaptic proteins (post-synaptic density protein-95 and Ca²⁺/calmodulin-dependent protein kinase II) in the hippocampus and cerebral cortex, respectively, in response to different treatments. Western blotting analysis showed that there were significant decreases in the expression of these representative synaptic proteins in the hippocampus and cerebral cortex of d-gal-treated mice. Interestingly, these decreased expression levels of synaptic proteins could be reversed by PSPC. The levels of expression of these representative synaptic proteins in mice treated with PSPC alone were not significantly different from those in untreated mice. The results of this study suggested that memory impairment and synaptic protein loss in d-gal-treated mice may be improved by treatment with PSPC.     

Effects of exposure of mice to hindlimb unloading on leukocyte subsets and sympathetic nervous system activity

The hindlimb unloading (HU) rodent model was developed to simulate some of the aspects of spaceflight conditions. Our previous studies showed that exposure to HU for 48 h (h) followed by bacterial challenge, reduces the ability of mice to resist infection. The purpose of this study was to investigate the physiological changes in mice during the 48 h of exposure to HU to understand the mechanisms involved in the increased susceptibility to infection observed in mice subjected to these conditions. Female Swiss Webster mice were hindlimb-unloaded during 48 h. Blood samples, spleen and peritoneal cells were removed before and after 18 or 48 h of HU-exposure. Leukocyte subset analysis was performed in spleen and peritoneal cells by flow cytometry, and catecholamine levels were measured in plasma and whole spleen by a catecholamine enzyme immunoassay. Catecholamine levels measured in plasma and spleen were significantly greater in mice exposed to HU compared to control. This increase coincided with significant reductions in spleen size in the HU group. Flow cytometric analyses showed a significant reduction of splenic CD19 + B-cells and NK1.1+ cells in mice exposed to HU with a concomitant increase in T-cells. These results suggest that exposure to HU increases the activity of the sympathetic nervous system (SNS) and induces lymphocyte sub-population changes that may contribute to the deregulation of immunity seen in mice exposed to HU and, more importantly may predispose the otherwise healthy host to the subsequent reduced ability to resist infections.     

Memory-enhancing corticosterone treatment increases amygdala norepinephrine and Arc protein expression in hippocampal synaptic fractions

Considerable evidence indicates that glucocorticoid hormones enhance the consolidation of memory for emotionally arousing events through interactions with the noradrenergic system of the basolateral complex of the amygdala (BLA). We previously reported that intra-BLA administration of a β-adrenoceptor agonist immediately after inhibitory avoidance training enhanced memory consolidation and increased hippocampal expression of the protein product of the immediate early gene activity-regulated cytoskeletal-associated protein (Arc). In the present experiments corticosterone (3 mg/kg, i.p.) was administered to male Sprague-Dawley rats immediately after inhibitory avoidance training to examine effects on long-term memory, amygdala norepinephrine levels, and hippocampal Arc expression. Corticosterone increased amygdala norepinephrine levels 15 min after inhibitory avoidance training, as assessed by in vivo microdialysis, and enhanced memory tested at 48 h. Corticosterone treatment also increased expression of Arc protein in hippocampal synaptic tissue. The elevation in BLA norepinephrine appears to participate in corticosterone-influenced modulation of hippocampal Arc expression as intra-BLA blockade of β-adrenoceptors with propranolol (0.5 μg/0.2 μL) attenuated the corticosterone-induced synaptic Arc expression in the hippocampus. These findings indicate that noradrenergic activity at BLA β-adrenoceptors is involved in corticosterone-induced enhancement of memory consolidation and expression of the synaptic-plasticity-related protein Arc in the hippocampus.     

围生期双酚A暴露对不同性别子代小鼠行为的影响

探讨围生期母体双酚A(bisphenol A, BPA)暴露对幼年期(生后21~30天, postnatal day 21~30, PND 21~30)和青年期(生后56~63天, PND 56~63)不同性别子代小鼠行为的影响。母鼠从妊娠第7天至断乳前(产后21天)进行BPA(0.05、0.5、5、50 mg/kg/day)灌胃染毒, 同时设对照组。每个剂量组分别在PND 21和PND 56开始测试雌雄子代小鼠各项行为。以旷场行为检测小鼠的自发活动及探究行为, 以高架十字迷宫检测小鼠的焦虑行为, 以水迷宫检测小鼠的空间学习记忆能力, 以跳台检测小鼠的被动回避记忆行为。结果表明, BPA使PND 21雌雄子鼠和PND 56雄性子鼠自发活动减少(p<0.05或p<0.01), 理毛和站立行为发生性别分化(p<0.05或p<0.01); PND 21子鼠的3分钟跑动格数有明显的剂量效应关系, 其中5~50 mg/kg/day组特别显著。BPA显著增加PND 21雌雄子鼠和PND56雌性子鼠在高架十字迷宫中进入开放臂次数和停留时间(p<0.05或p<0.01)并减少封闭臂的进入时间, 但没有明显的剂量效应关系; BPA减少PND 56雄性子鼠开放臂的进入并增加其封闭臂的进入, 干扰了幼年期和青年期小鼠焦虑行为的性别分化。BPA剂量依赖性地延长PND 21和PND 56雄性子鼠在水迷宫搜索平台的平均距离, 其中5~50 mg/kg/day剂量组具有差异显著性(p<0.05或p<0.01), 但对雌性子鼠空间学习记忆行为没有影响。此外, 5~50 mg/kg/day BPA增加PND 21雄性子鼠在跳台实验中的错误次数并缩短其跳下平台潜伏期, PND 56雌雄子鼠的被动回避记忆仅被50 mg/kg/day BPA减弱。以上结果提示, 围生期BPA暴露可影响子代小鼠幼年期和青年期的多种行为及行为的性别差异, 不同行为对BPA的敏感程度不同, 其中以自发活动和探究行为最敏感。     

慢性应激诱导的抑郁大鼠纹状体par-4基因的表达

为研究慢性温和应激诱导的抑郁大鼠纹状体内前列腺凋亡反应蛋白(prostate apoptosis response-4, par-4)的表达, 及甲基化是否参与par-4基因表达的调控, 将10周龄大鼠随机分为实验组和对照组, 实验组接受慢性温和应激, 对照组不接受实验性处理。于大鼠13周龄时, 采用强迫游泳、糖水偏爱测验测定大鼠的抑郁水平, 以实时定量PCR检测纹状体par-4及多巴胺D2受体(Dopamine receptor D2, DRD2) mRNA表达水平, 免疫印迹法检测纹状体par-4蛋白质表达水平, 用亚硫酸盐测序法检测par-4基因启动子区甲基化水平。结果发现, 与对照组大鼠相比, 实验组大鼠漂浮时间延长, 糖水偏爱率降低, 脑纹状体par-4、DRD2 mRNA及par-4蛋白质表达水平均降低, par-4基因启动子区甲基化水平两组差异不显著。提示慢性温和应激诱导大鼠产生了抑郁样行为, 并能抑制纹状体par-4基因的表达, 而基因甲基化可能并不参与其调控机制。     

Chronic administration of troxerutin protects mouse brain against d-galactose-induced impairment of cholinergic system

Previous evidence showed that administration of d-galactose (d-gal) increased ROS production and resulted in impairment of cholinergic system. Troxerutin, a natural bioflavonoid, has been reported to have many benefits and medicinal properties. In this study, we evaluated the protective effect of troxerutin against d-gal-induced impairment of cholinergic system, and explored the potential mechanism of its action. Our results displayed that troxerutin administration significantly improved behavioral performance of d-gal-treated mice in step-through test and morris water maze task. One of the potential mechanisms of this action was decreased AGEs, ROS and protein carbonyl levels in the basal forebrain, hippocampus and front cortex of d-gal-treated mice. Furthermore, our results also showed that troxerutin significantly inhibited cholinesterase (AchE) activity, increased the expression of nicotinic acetylcholine receptor alpha 7 (nAchRα7) and enhanced interactions between nAchRα7 and either postsynaptic density protein 95 (PSD95) or N-methyl-d-aspartate receptors subunit 1 (NMDAR1) in the basal forebrain, hippocampus and front cortex of d-gal-treated mice, which could help restore impairment of brain function.     

替罗非班不同给药途径对DM合并急性STEMI患者PCI术后血小板α-颗粒膜蛋白及心肌灌注水平的影响

为探讨替罗非班不同给药途径对糖尿病（DM）合并急性ST段抬高型心肌梗死（STEMI）患者PCI术后血小板α-颗粒膜蛋白及心肌灌注水平的影响,对149例DM合并急性STEMI患者进行研究,测定并比较经静脉（A组）、冠脉给药途径（B组）和无替罗非班（C组）的患者术前及术中应用替罗非班后血小板α-颗粒膜蛋白GMP140浓度、造影结果、心肌酶及肌钙蛋白I水平峰值及峰值时间、心电图变化。结果显示A、B两组术中血小板α-颗粒膜蛋白浓度较术前明显降低（P〈0．05）,且B组较A组降低更明显（P〈0．05）,而C组未见明显变化（P〉0．05）,A、B两组术后即刻TIMI血流、2h sumSTR、心肌酶及肌钙蛋白Ⅰ峰值及峰值时间的变化均优于C组（P〈0．05）,且B组优于A组（P〈0．05）。因此,替罗非班可以降低血小板α-颗粒膜蛋白浓度和改善心肌灌注水平,与静脉途径给药相比,经冠脉给药更具有优势。     

Odor preference learning and memory modify GluA1 phosphorylation and GluA1 distribution in the neonate rat olfactory bulb: testing the AMPA receptor hypothesis in an appetitive learning model

An increase in synaptic AMPA receptors is hypothesized to mediate learning and memory. AMPA receptor increases have been reported in aversive learning models, although it is not clear if they are seen with memory maintenance. Here we examine AMPA receptor changes in a cAMP/PKA/CREB-dependent appetitive learning model: odor preference learning in the neonate rat. Rat pups were given a single pairing of peppermint and 2 mg/kg isoproterenol, which produces a 24-h, but not a 48-h, peppermint preference in the 7-d-old rat pup. GluA1 PKA-dependent phosphorylation peaked 10 min after the 10-min training trial and returned to baseline within 90 min. At 24 h, GluA1 subunits did not change overall but were significantly increased in synaptoneurosomes, consistent with increased membrane insertion. Immunohistochemistry revealed a significant increase in GluA1 subunits in olfactory bulb glomeruli, the targets of olfactory nerve axons. Glomerular increases were seen at 3 and 24 h after odor exposure in trained pups, but not in control pups. GluA1 increases were not seen as early as 10 min after training and were no longer observed 48 h after training when odor preference is no longer expressed behaviorally. Thus, the pattern of increased GluA1 membrane expression closely follows the memory timeline. Further, blocking GluA1 insertion using an interference peptide derived from the carboxyl tail of the GluA1 subunit inhibited 24 h odor preference memory providing causative support for our hypothesis. PKA-mediated GluA1 phosphorylation and later GluA1 insertion could, conjointly, provide increased AMPA function to support both short-term and long-term appetitive memory.     

Expression of VGLUTs contributes to degeneration and acquisition of learning and memory

Vesicular glutamate transporters (VGLUTs), which include VGLUT1, VGLUT2 and VGLUT3, are responsible for the uploading of L-glutamate into synaptic vesicles. The expression pattern of VGLUTs determines the level of synaptic vesicle filling (i.e., glutamate quantal size) and directly influences glutamate receptors and glutamatergic synaptic transmission; thus, VGLUTs may play a key role in learning and memory in the central nervous system. To determine whether VGLUTs contribute to the degeneration or acquisition of learning and memory, we used an animal model for the age-related impairment of learning and memory, senescence-accelerated mouse/prone 8 (SAMP8). KM mice were divided into groups based on their learning and memory performance in a shuttle-box test. The expression of VGLUTs and synaptophysin (Syp) mRNA and protein in the cerebral cortex and hippocampus were investigated with real-time fluorescence quantitative PCR and western blot, respectively. Our results demonstrate that, in the cerebral cortex, protein expression of VGLUT1, VGLUT2, VGLUT3 and Syp was decreased in SAMP8 with age and increased in KM mice, which displayed an enhanced capacity for learning and memory. The protein expression of VGLUT2 and Syp was decreased in the hippocampus of SAMP8 with aging. The expression level of VGLUT1 and VGLUT2 proteins were highest in KM mouse group with a 76-100% avoidance score in the shuttle-box test. These data demonstrate that protein expression of VGLUT1, VGLUT2 and Syp decreases age-dependently in SAMP8 and increases in a learning- and memory-dependent manner in KM mice. Correlation analysis indicated the protein expression of VGLUT1, VGLUT2 and Syp has a positive correlation with the capacity of learning and memory.     

The in vitro immunomodulatory effects of glyconutrients on peripheral blood mononuclear cells of patients with chronic fatigue syndrome

In humans, eight monosaccharides are required for the synthesis of glycoproteins. Dietary supplements that supply these crucial sugars are known as glyconutrients. A glyconutrient compound was added to Peripheral Blood Mononuclear Cells (PBMC) isolated from normal controls and patients with the Chronic Fatigue Syndrome (CFS), a disease associated with immune dysregulation. The in vitro immunomodulatory effects were investigated. Cell surface expression of the glycoproteins CD5, CD8, and CD11a were significantly lower in patients with CFS compared to normal controls. Addition of glyconutrient homogenate to PBMC from patients with CFS stimulated with phytohemagglutinin significantly increased the expression of each glycoprotein. Furthermore, natural killer (NK) cell function was reduced in CFS patients. The glyconutrient preparation significantly enhanced NK cell activity versus human herpes virus 6 (HHV-6)-infected H9 cells in an 8 h⁵¹Cr release assay compared to placebo for PBMC from patients with CFS (p<.01). Finally, apoptosis was significantly higher in patients with CSF. The percentage of apoptotic cells was significantly decreased in PBMC from patients with CFS that had been incubated for 48 h with glyconutrients. Thus, glyconutrients improved abnormal immune parameters in vitro in patients with CFS. Dr. See is an Independent Mannatech Associate.     

Effects of emotion on oxytocin,prolactin, and ACTH in women

Research on both non-human mammals and humans has raised interest in the role that oxytocin may play in human attachment and attachment-related emotions. This study examined changes in plasma oxytocin, prolactin, and ACTH concentrations in response to laboratory-induced positive and negative emotions related to close, interpersonal relationships. Participants were 32 female volunteers recruited from university communities. During positive emotion induction, oxytocin decreased over time (F(1,3) = 4.41, p < 0.007), prolactin increased (F(1,3) = 4.80, p < 0.004) and ACTH remained constant. During negative emotion induction, prolactin levels increased (F(1,3) = 2.81, p < 0.05), ACTH decreased only after the induction terminated (F(1,3) = 4.02, p < 0.01) and oxytocin remained constant. While oxytocin decreased during positive emotion, this finding contrasted previous research that showed decreases in response to negative emotion. In conclusion, plasma oxytocin levels were not reliably altered by positive or negative emotion induction. While prolactin and ACTH were expected to decrease over time due to diurnal variation, they instead either increased or remained level during emotion induction, or decreased only after the induction. Overall, the degree of change in circulating hormones in response to happy and sad emotions was very small and possibly not functionally significant.     

内隐序列学习中的渐进意识：来自习得知识的发展与遗忘的证据

内隐学习过程中习得知识的发展变化是内隐学习的一个重要特征。本研究采用序列反应时范式通过操纵学习进程（实验一）和学习与测验间的时间间隔（实验二）来考察内隐序列学习进程中习得知识的发展与遗忘特征,结果发现,（1）内隐序列学习中习得的无意识知识多于意识知识;（2）随着学习的推进,意识知识逐渐增加,而无意识知识则呈减弱趋势,证实了内隐学习的长时功效;（3）习得的无意识知识具有抗遗忘性,而意识知识在间隔8小时之后才开始出现遗忘。     

Functional and connectivity changes during working memory in Huntington’s disease: 18 month longitudinal data from the IMAGE-HD study

Background

This study aimed to characterize, for the first time, 18 month longitudinal changes in both functional activation and functional connectivity during working memory in premanifest Huntington’s disease (pre-HD) and symptomatic HD (symp-HD).

Methods

Functional magnetic resonance imaging (fMRI) was used to investigate longitudinal changes in neuronal activity during working memory performance via an N-BACK task (0-BACK and 1-BACK) in 27 pre-HD, 17 symp-HD, and 23 control participants. Whole-brain analysis of activation and region-of-interest analysis of functional connectivity was applied to longitudinal fMRI data collected at baseline and 18 months follow-up.

Results

Compared with controls, the pre-HD group showed significantly increased activation longitudinally during 1-BACK versus 0-BACK in the lateral and medial prefrontal, anterior cingulate, primary motor, and temporal areas cortically, and caudate and putamen subcortically. Pre-HD far from onset, compared with controls, showed further longitudinal increases in the right and left dorsolateral prefrontal cortex (DLPFC). Longitudinal increased activation in anterior cingulate and medial primary motor areas were associated with disease burden in the pre-HD group. Moreover, in pre-HD increased activation over time in primary motor and putamen regions were associated with average response time during 1-BACK performance. During 1-BACK, functional connectivity between the right DLPFC and posterior parietal, anterior cingulate, and caudate was significantly reduced over 18 months only in the pre-HD group.

Conclusions

Longitudinal reductions in connectivity over 18 months may represent an early signature of cortico-cortical and cortico-striatal functional disconnectivity in pre-HD, whereas the concomitant increased cortical and subcortical activation may reflect a compensatory response to the demands for cognitive resources required during task performance. Our findings demonstrate that functional imaging modalities have the potential to serve as sensitive methods for the assessment of cortical and subcortical responses to future treatment measures.     

视知觉压力在基本心理能力老化中的作用

信息降格说认为, 感觉功能老化使认知系统难以获得良好的信息输入, 并必须牺牲有限的认知资源获得更好的刺激信息, 使能用于认知加工的资源不足, 造成认知老化。为探讨感觉功能对基本心理能力老化的作用, 该研究采用2(年龄组：年轻、老年组)×4(视知觉压力水平：高、中、低、无噪音)的混合设计, 考察年轻、老年组在相同视知觉压力下基本心理能力的年龄差异。结果发现和无噪音条件相比, 相同视知觉压力下基本心理能力(数字能力、归纳推理能力)的年龄差异减小, 甚至消失, 一定程度上支持信息降格说。视觉功能衰退可能是影响基本心理能力老化的重要因素, 但这种作用受认知资源的调节。     

Mice lacking the ERK1 isoform of MAP kinase are unimpaired in emotional learning

The extracellular signal-regulated kinases (ERKs) are members of the mitogen-activated protein kinase (MAPK) superfamily of enzymes and have recently garnered considerable attention in the field of learning and memory. ERK activation has been shown to be required for the induction of long-term potentiation (LTP) in the rat hippocampus and for the formation of associative and spatial memories in both the rat and the mouse. However, the individual roles for the two isoforms of ERK have yet to be deciphered. To investigate the specific contribution of the ERK1 (p44) isoform of MAPK to mammalian learning, we performed a general behavioral and physiological characterization of mice lacking the ERK1 gene. The ERK1-null animals demonstrated significantly higher levels of activity in the open field test. However, we observed no other discernible deficits in the ERK1 knockout mice in our behavioral testing. Specifically, no differences were observed in the acquisition or retention (24 h and 2 wk after training) of either contextual or cue fear conditioning between the ERK1^−/− and their wild-type littermate controls. In addition, no learning phenotype was observed in the passive avoidance test. When hippocampal slices were analyzed, we found no deficits in baseline synaptic transmission or in tetanus-induced LTP in hippocampal area CA1. We found no apparent compensatory changes in the expression of ERK2 (p42 MAPK). We conclude that hippocampus- and amygdala-dependent emotional learning does not depend critically on the activity of ERK1.     

Behavioral and physiological responses of young horses to different weaning protocols: a pilot study

In this study, effects of weaning on behavioral and physiological stress parameters in young horses (foals) were determined. Foals were weaned either simultaneously without the presence of adult horses (group A, n?=?6), or in the presence of two adult females familiar but unrelated to the foals (group B, n?=?5), or weaned consecutively by removing two mother horses per day (group C, n?=?6). Behavior, locomotion, salivary cortisol concentration, beat-to-beat (RR) interval, heart rate variability (HRV) and weight were determined. Group A foals lost weight for 2 days (mean?±?SEM) -?8.3?±?1.6?kg, p?相似文献   

Differential involvement of hippocampal calcineurin during learning and reversal learning in a Y-maze task

The regulation and function of the calcium-dependent phosphatase calcineurin (CaN, protein phosphatase 2B) in learning and memory remain unclear, although recent work indicates that CaN may play a differential role in training and reversal training. To gain more insight into the involvement of CaN in these two types of learning, hippocampal CaN activity, protein levels, and expression patterns were studied in mice subjected to a reference memory version of the Y-maze task. We show that (1) training but not habituation induces a decrease in cytosolic CaN activity, (2) the recovery of cytosolic CaN activity is reversal training specific and does not reflect normal restoration of basal levels unrelated to subsequent learning, (3) cytosolic protein levels for the catalytic subunit of CaN (CaNA) are decreased at the early phase of training, but not at the early phase of reversal training, (4) CaNA immunoreactivity in the dorsal hippocampus is enhanced in the CA1 and CA3 area (but not in the dentate gyrus [DG] or subiculum [SUB]) only during reversal training. These findings indicate that memory formation is accompanied by reduced CaN activity, whereas adapting to changes in a familiar environment is accompanied by restored CaN activity. Moreover, reversal training selectively affects hippocampal CA3 and CA1 regions, suggesting a specific function of these hippocampal subregions in reversal learning.     

Late expression of brain-derived neurotrophic factor in the amygdala is required for persistence of fear memory

In many instances, increase in neuronal activity can induce biphasic secretion of a modulator. The initial release of the modulator triggers the induction of synaptic plasticity, whereas the second-phase release reinforces the efficacy of synaptic transmission and growth of dendrites and axons. In this study, we showed that fear conditioning not only induced the first but also a second peak of brain-derived neurotrophic factor (BDNF) expression. Fluorescent immunohistostaining confirmed that BDNF expression increased at 1 and 12 h after conditioning and returned to baseline at 30 h after conditioning. Mature BDNF expression increased in a similar manner. TrkB-IgG or K252a infusion before training impaired fear memory on days 1 and 7 after training. In contrast, TrkB-IgG or K252a infusion 9 h after fear conditioning did not affect memory retention on day 1 after training but impaired fear memory on day 7 after training. Fear conditioning significantly enhanced Zif268 expression in the amygdala at 12 h after training; this enhanced expression was completely inhibited by TrkB-IgG infusion 9 h after training. The level of growth-associated protein 43 (GAP-43), a marker of newly formed synapses, in the amygdala increased 7 days after fear conditioning. Moreover, conditioned rats had higher AMPA/NMDA ratio than unpaired rats. These results suggest that consolidated memory could be continuously modulated by previous molecular changes produced during memory acquisition.