成年期双酚A暴露对小鼠行为的影响

探究成年期环境雌激素双酚A(bisphenol A, BPA)暴露对不同性别小鼠行为的影响。出生5周的小鼠灌胃染毒BPA (40、400 µg/kg/d), 同时设对照组。染毒8周后, 以开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和探究行为, 以水迷宫检测小鼠的空间学习记忆行为, 以跳台检测小鼠的被动回避记忆行为。结果显示, BPA暴露不影响同性别小鼠在开场中的各种行为, 但消除了悬空站立和扶壁站立频率的性别差异。高架十字迷宫行为测试中, BPA暴露显著减少雄鼠进入开放臂的次数和停留时间(p<0.05和p<0.01), 却显著增加雌鼠进入开放臂的次数和停留时间(p<0.05和p<0.01); 同时, BPA暴露显著减少雄鼠(p<0.05和p<0.01)却增加雌鼠在中央区的探头次数(p<0.01), 消除甚至反向诱导成年小鼠焦虑行为和探究行为的性别分化。BPA (40 µg/kg/d)暴露显著延长成年雄鼠在水迷宫中搜寻平台的平均距离(p<0.05), 但对雌鼠没有影响, BPA因此消除了正常成年小鼠空间记忆行为的性别差异。BPA(40 µg/kg/d)暴露显著缩短了雄鼠在遭电击24h后跳下平台的潜伏期(p<0.05), 但对雌鼠没有明显影响, 并因此诱导成年小鼠被动回避行为的性别差异。以上结果表明, 成年期BPA 暴露可性别特异性地影响小鼠的多种行为, 干扰成年小鼠行为的性别差异。     

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。     

加工水平和呈现时间对错误记忆的影响

在DRM范式下,通过操纵加工水平和呈现时间,考察它们对错误记忆和真实记忆的影响.结果发现,加工水平对错误记忆没有影响,随着对词表加工水平的提高,错误再认率差异不显著.而加工水平对正确记忆有显著影响,不同加工水平间的正确再认率差异极其显著.错误记忆与正确记忆在加工水平上表现出了分离.在较慢呈现时间下,呈现时间对错误记忆和正确记忆的影响均不显著.     

环境雌激素双酚A对成年小鼠学习记忆和突触结构的影响*

双酚A (bisphenol, BPA)是一种广泛存在的环境内分泌干扰物,它可与雌激素受体结合干扰内源性雌激素对中枢神经系统的调控作用。本研究通过将10周龄小鼠灌胃染毒BPA (0.4、4、40 mg/kg/day)3个月,研究长期BPA暴露对成年小鼠记忆行为和突触可塑性的影响。开场行为测试结果表明, BPA (0.4、4、40 mg/kg/day)增加雄性的站立次数和理毛频率, BPA (4 mg/kg/day)却显著减少雌鼠的站立次数。水迷宫和被动回避行为模型检测显示, BPA主要损伤雄鼠的空间学习记忆和被动回避记忆。通过制备海马CA1区超薄切片后,电镜观测发现, BPA (0.4、40 mg/kg/day)暴露降低雄鼠海马CA1区突触数密度,缩短雄鼠突触前活性带长度,减小雄鼠突触后致密体(PSD)厚度,增加雄鼠突触间隙宽度。进一步用Western blot方法检测突触前、后的标志性蛋白Synapsin I和PSD95以及兴奋性氨基酸NMDA受体NR1亚基和AMPA受体GluR1亚基蛋白的表达,发现BPA暴露致雄鼠Synapsin I、PSD95、NR1蛋白表达水平下调。而BPA对雌鼠的记忆行为、突触形态、突触蛋白和受体蛋白均没有明显作用。以上结果提示长期B PA暴露性别特异性地影响成年小鼠的活动性和探究行为,损伤雄鼠的学习记忆,这些作用可能通过下调突触蛋白和NMDA受体的表达而负性影响突触结构可塑性,最终影响雄鼠的学习记忆功能。     

表象编码对基于词表的错误记忆的影响

采用DRM范式,探讨不同表象编码时间和不同表象编码加工程度对基于词表的错误记忆的影响。在学习阶段,被试对呈现的词进行记忆。在测试阶段,被试在每个词列表学习结束后立即对该词列表进行自由回忆,分心任务结束后进行再认测试。实验结果发现：（1）被试在5秒编码条件下的错误记忆率显著低于3秒编码条件下的错误记忆率;（2）在5秒表象编码时间条件下,深加工组被试的错误记忆率显著低于浅加工组。这说明在较长的编码时间里,时间越长记住的细节信息越多,错误记忆率越低;加工程度越深,错误记忆率越低。     

表象编码对基于词表的错误记忆的影响

采用DRM范式,探讨不同表象编码时间和不同表象编码加工程度对基于词表的错误记忆的影响。在学习阶段,被试对呈现的词进行记忆。在测试阶段,被试在每个词列表学习结束后立即对该词列表进行自由回忆,分心任务结束后进行再认测试。实验结果发现：（1）被试在5秒编码条件下的错误记忆率显著低于3秒编码条件下的错误记忆率;（2）在5秒表象编码时间条件下,深加工组被试的错误记忆率显著低于浅加工组。这说明在较长的编码时间里,时间越长记住的细节信息越多,错误记忆率越低;加工程度越深,错误记忆率越低。     

抗精氨酸加压素单克隆抗体对小鼠行为的影响

本工作在我们已报道的外源性精氨酸加压素([Arg~8] Vasoprpssin,AVP)促进小鼠记忆巩固结果的基础上,应用本实验室研制成功的抗精氨酸加压素单克隆抗体(Monoclonal Antibody to[Arg~8]Vasopressin,AVPMcAb)中枢及外周注射,观察小鼠内源性AVP对记忆巩固的影响。结果为:中枢注射AVP-McAb1.5—4.5毫微克/鼠后,小鼠抑制性回避反应的潜伏期和生理盐水对照组相比,均显著缩短(P<0.05);而外周尾静脉注射AVPMcAb0.15—1.50微克/鼠对小鼠此行为反应无影响,与生理盐水组对比,潜伏期无显著性差异。这提示,中枢内源性生理水平的加压素可能对小鼠记忆巩固起易化作用,而外周的加压素在生理条件下可能无此效应。 小鼠游泳试验中,训练后立即中枢注射AVPMcAb也降低小鼠游泳平衡的反应。这暗示,中枢内源性加压素在该行为模式上也参与记忆的调制过程。     

高压氧对小鼠学习记忆及脑细胞形态结构的影响

实验用两种行为模型（旷场行为模型和Ｙ－迷宫分辨学习模型）观察了幼龄小鼠在不同压力的高压氧处理后,对新异环境的探究行为和自发活动情况,以及学习记忆能力的变化;并用ＸＹ－生物医学电脑图像分析仪分析了与学习记忆相关的脑区（大脑皮层、海马）神经元密度,细胞核面积,胞核／胞浆比值的变化。结果表明：（１）与对照组相比,吸０.１ＭＰａ高压氧的幼鼠学习记忆能力明显提高,相关脑区的神经元密度、细胞核面积、胞核／浆比均显著增加。（２）吸０.２５ＭＰａ高压氧的幼鼠学习记忆能力与对照组相比无明显变化,但其在新异环境中的自发行为明显减少。提示：慢性吸入０.１ＭＰａ高压氧有利于促进幼鼠脑的生长发育,增强脑功能活动。     

误导信息干扰引发的错误记忆研究

本研究借鉴GSS的测验程序,以学习材料视觉呈现、团体实验的形式,在人工条件下模拟了目击者记忆过程．通过操纵材料呈现时间（20秒、40秒）与测验次数（初测、重测）两个变量,考察了该情境下错误记忆的内在机制及其动态变化特点。并进一步研究该情境下受暗示性与社会期望、自尊、心理控制源以及视觉想象生动性的关系。实验发现,40秒比20秒条件下,真实记忆效果更好,错误记忆效果更少;重测比初测时错误记忆更多。可见,真实记忆量的差异是影响错误记忆的主要因素：错误记忆较为顽固,产生后呈增加趋势。相关分析还发现,受暗示性的各种指标（yiddl、yidd2、yidd3和shift）与社会期望、自尊、心理控制源、视觉想象生动性等因素均无显著相关．与桔试的自由回忆成绩成显著负相关。     

中文阅读中的字词激活模式:来自提示词边界延时效应的证据

研究采用眼动随动显示技术,通过操控提示正确/错误词边界线索的延迟时间,考察汉语阅读中汉字、词汇加工与词切分的时间特性。实验1发现,提示词n+1边界不影响总阅读时间,但能积极影响词兴趣区内的眼动数据,这种影响随着提示延迟时间的增加而逐步减弱;提示错误的词n+1的边界线索对总阅读时间的影响则随提示延迟时间的增加呈现倒"U"型的变化趋势。实验2发现,提示词n边界不影响总阅读时间,但却消极影响词兴趣区内的眼动数据,这种消极影响并没有随着提示延迟时间的增加而减弱;提示错误的词n边界对总阅读时间和眼动数据均产生消极的影响,且这种影响都随着提示延迟时间的增加而减弱。综合两项实验的结果可以推测,单一的向上反馈假设和整体假设都不能全面解释阅读中的字词加工过程,汉字加工与词汇加工间存在交互激活过程。     

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.     

Deletion of the GluA1 AMPA receptor subunit impairs recency-dependent object recognition memory

Deletion of the GluA1 AMPA receptor subunit impairs short-term spatial recognition memory. It has been suggested that short-term recognition depends upon memory caused by the recent presentation of a stimulus that is independent of contextual-retrieval processes. The aim of the present set of experiments was to test whether the role of GluA1 extends to nonspatial recognition memory. Wild-type and GluA1 knockout mice were tested on the standard object recognition task and a context-independent recognition task that required recency-dependent memory. In a first set of experiments it was found that GluA1 deletion failed to impair performance on either of the object recognition or recency-dependent tasks. However, GluA1 knockout mice displayed increased levels of exploration of the objects in both the sample and test phases compared to controls. In contrast, when the time that GluA1 knockout mice spent exploring the objects was yoked to control mice during the sample phase, it was found that GluA1 deletion now impaired performance on both the object recognition and the recency-dependent tasks. GluA1 deletion failed to impair performance on a context-dependent recognition task regardless of whether object exposure in knockout mice was yoked to controls or not. These results demonstrate that GluA1 is necessary for nonspatial as well as spatial recognition memory and plays an important role in recency-dependent memory processes.     

Emotionally arousing pictures increase blood glucose levels and enhance recall

Arousal enhances memory in human participants and this enhancing effect is likely due to the release of peripheral epinephrine. As epinephrine does not readily enter the brain, one way that peripheral epinephrine may enhance memory is by increasing circulating blood glucose levels. The present study investigated the possibility that emotionally arousing color pictures would improve memory and elevate blood glucose levels in human participants. Blood glucose levels were measured before, 15 min, and 30 min after male university students viewed 60 emotionally arousing or relatively neutral pictures. Participants viewed each picture for 6 s and then had 10 s to rate the arousal (emotional intensity) and valence (pleasantness) of each picture. A free-recall memory test was given 30 min after the last picture was viewed. Although the emotionally arousing and neutral picture sets were given comparable valence ratings, participants who viewed the emotionally arousing pictures rated the pictures as being more arousing, recalled more pictures, and had higher blood glucose levels after viewing the pictures than did participants who viewed the neutral pictures. These findings indicate that emotionally arousing pictures increase blood glucose levels and enhance memory, and that this effect is not due to differences in the degree of pleasantness of the stimuli. These findings support the possibility that increases in circulating blood glucose levels in response to emotional arousal may be part of the biological mechanism that allows emotional arousal to enhance memory.     

Time-based prospective memory difficulties in children with ADHD and the role of time perception and working memory

Time-based prospective memory (PM) is the ability to remember to perform an intended action at a given time in the future. It is a competence that is crucial for effective performance in everyday life and may be one of the main causes of problems for individuals who have difficulty in planning and organizing their life, such as children with attention deficit/hyperactivity disorder (ADHD). This study systematically examines different aspects of time-based PM performance in a task that involves taking an action at a given future time in a group of 23 children with ADHD who were compared with a matched group of typically-developing (TD) children. The children were asked to watch a cartoon and then answer a questionnaire about its content (ongoing task). They were also asked to press a key every 2 minutes while watching the cartoon (PM task). The relationships of time perception and verbal working memory with PM performance were examined by administering appropriate tasks. The results showed that the children with ADHD were less accurate than the TD children in the PM task and exhibited less strategic time-monitoring behavior. Time perception was found to predict PM accuracy, whereas working memory was mainly involved in time-monitoring behavior, but this applied more to the TD group than to the ADHD group, suggesting that children with ADHD are less able to use their cognitive resources when meeting a PM request.     

心理应激的免疫抑制作用及其与神经内分泌反应的相关性

以给予经定时喂水训练大鼠空瓶刺激为情绪性心理应激源,研究了此情绪应激对大鼠特异性原发体液免疫反应的影响及其可能的作用机制。结果表明每次10分钟,共14次的情绪应激显著降低大鼠抗特异性抗原OVA的抗体水平及脾脏指数,而显著增高血肾上腺素、去甲肾上腺素和皮质酮水平。研究还发现去甲肾上腺素与抗特异性抗原OVA的抗体水平呈显著负相关。该研究证实了情绪性心理应激对大鼠体液免疫功能的抑制作用,并提示交感神经系统可能参与了此免疫调节作用。     

GAP-43 gene expression regulates information storage

Previous reports have shown that overexpression of the growth- and plasticity-associated protein GAP-43 improves memory. However, the relation between the levels of this protein to memory enhancement remains unknown. Here, we studied this issue in transgenic mice (G-Phos) overexpressing native, chick GAP-43. These G-Phos mice could be divided at the behavioral level into “spatial bright” and “spatial dull” groups based on their performance on two hidden platform water maze tasks. G-Phos dull mice showed both acquisition and retention deficits on the fixed hidden platform task, but were able to learn a visible platform task. G-Phos bright mice showed memory enhancement relative to wild type on the more difficult movable hidden platform spatial memory task. In the hippocampus, the G-Phos dull group showed a 50% greater transgenic GAP-43 protein level and a twofold elevated transgenic GAP-43 mRNA level than that measured in the G-Phos bright group. Unexpectedly, the dull group also showed an 80% reduction in hippocampal Tau1 staining. The high levels of GAP-43 seen here leading to memory impairment find its histochemical and behavioral parallel in the observation of Rekart et al. (Neuroscience 126: 579–584) who described elevated levels of GAP-43 protein in the hippocampus of Alzheimer’s patients. The present data suggest that moderate overexpression of a phosphorylatable plasticity-related protein can enhance memory, while excessive overexpression may produce a “neuroplasticity burden” leading to degenerative and hypertrophic events culminating in memory dysfunction.     

Integrated memory for objects, places, and temporal order: evidence for episodic-like memory in mice

Human episodic memory refers to the recollection of an unique past experience in terms of what happened, and where and when it happened. Factoring out the issue of conscious recollection, episodic memory, even at the behavioral level, has been difficult to demonstrate in non-human mammals. Although, it was previously shown that rodents can associate what and when or what and where information given on unique trials, it proved to be difficult to demonstrate memory for what, where, and when simultaneously in mammals, without using extensive training procedures, which might induce semantic rather than episodic memory recall. Towards the goal of an animal model of human episodic memory we designed an three-trial object exploration task in which different versions of the novelty-preference paradigm were combined to subsume (a) object recognition memory, (b) the memory for locations in which objects were explored, and (c) the temporal order memory for object presented at distinct time points. We found that mice spent more time exploring two "old familiar" objects relative to two "recent familiar" objects, reflecting memory for what and when and concomitantly directed more exploration at a spatially displaced "old familiar" object relative to a stationary "old familiar" object, reflecting memory for what and where. These results suggest that during a single test trial the mice were able to (a) recognize previously explored objects, (b) remember the location in which particular objects were previously encountered, and (c) to discriminate the relative recency in which different objects were presented. According to the currently discussed behavioral criteria for episodic-like memory in animals, our results suggest that mice are capable to form such higher order memories.     

Fluctuations in brain glucose concentration during behavioral testing: dissociations between brain areas and between brain and blood

Traditional beliefs about two aspects of glucose regulation in the brain have been challenged by recent findings. First, the absolute level of glucose in the brain's extracellular fluid appears to be lower than previously thought. Second, the level of glucose in brain extracellular fluid is less stable than previously believed. In vivo brain microdialysis was used, according to the method of zero net flux, to determine the basal concentration of glucose in the extracellular fluid of the striatum in awake, freely moving rats for comparison with recent hippocampal measurements. In addition, extracellular glucose levels in both the hippocampus and the striatum were measured before, during, and after behavioral testing in a hippocampus-dependent spontaneous alternation task. In the striatum, the resting extracellular glucose level was 0.71 mM, approximately 70% of the concentration measured previously in the hippocampus. Consistent with past findings, the hippocampal extracellular glucose level decreased by up to 30 +/- 4% during testing; no decrease, and in fact a small increase (9 +/- 3%), was seen in the striatum. Blood glucose measurements obtained during the same testing procedure and following administration of systemic glucose at a dose known to enhance memory in this task revealed a dissociation in glucose level fluctuations between the blood and both striatal and hippocampal extracellular fluid. These findings suggest, first, that glucose is compartmentalized within the brain and, second, that one mechanism by which administration of glucose enhances memory performance is via provision of increased glucose supply from the blood specifically to those brain areas involved in mediating that performance.     

Wistar rats show episodic-like memory for unique experiences

Human episodic memory refers to the recollection of an unique past experience in terms of its details, its locale, and temporal occurrence. Episodic memory, even in principle, has been difficult to demonstrate in non-verbal mammals. Previously, we provided evidence that mice are able to form an integrated memory for "what," "where," and "when" aspects of single experiences by combining different versions of the novelty-preference paradigm, i.e., object recognition memory, the memory for locations in which objects were explored, and the temporal order memory for objects presented at distinct time points. In the present series of experiments we evaluated whether this paradigm, with minor modifications, also works with rats. We found that rats spent more time exploring an "old familiar" object relative to a "recent familiar" object, suggesting that they recognized objects previously explored during separate trials and remembered their order of presentation. Concurrently, the rats responded differentially to spatial object displacement dependent on whether an "old familiar" or "recent familiar" object was shifted to a location, where it was not encountered previously. These results provide strong evidence that the rats established an integrated memory for "what," "where," and "when." We also found that acute stress impaired the animal's performance in the episodic-like memory task, which, however, could be partially reversed by the N-Methyl-D-aspartate-receptors agonist D-cycloserine.     

急性心理应激影响记忆效果：心理韧性的调节作用

研究选取56名大学生被试,通过特里尔社会应激测验、记忆和心理韧性测验来探究急性心理应激对大学生记忆效果的影响,以及心理韧性在二者关系中的调节作用。结果表明相对于非应激组,应激组大学生的整体记忆成绩更差,且应激组中的高应激反应大学生的记忆成绩比低应激反应者的记忆成绩更差;心理韧性可以调节应激反应与记忆成绩之间的关系,表现为高心理韧性者的记忆成绩显著好于低心理韧性者。研究进一步从认知加工资源分配与再分配的视角讨论了心理应激、心理韧性与记忆功能三者间的关系与启示。