自闭症动物模型社会互动行为的评估及干预研究进展

自闭症谱系障碍(autism spectrum disorder, ASD)是一种高度异质性的神经发育障碍,具有复杂的潜在遗传结构。然而,目前ASD正在研究的临床前试验主要通过啮齿类动物模型进行,以测试非药物干预及药物干预对ASD核心及相关症状的影响。本文从认知神经机制角度阐述影响社会互动行为的脑区;梳理社会互动的行为学测试实验;对ASD的核心和相关症状的有效非药物干预和药物干预进行综述,为下一步促进啮齿类动物模型临床前试验的发展提供参考方向。

Social avoidance behavior in male tree shrews and prosocial behavior in male mice toward unfamiliar conspecifics in the laboratory

Adult male tree shrews vigorously defend against intruding male conspecifics. However, the characteristics of social behavior have not been entirely explored in these males. In this study, male wild-type tree shrews(Tupaia belangeri chinensis)and C57 BL/6 J mice were first allowed to familiarize themselves with an open-field apparatus. The tree shrews exhibited a short duration of movement(moving) in the novel environment, whereas the mice exhibited a long duration of movement. In the 30 min social preference-avoidance test, target animals significantly decreased the time spent by the experimental tree shrews in the social interaction(SI)zone, whereas experimental male mice exhibited the opposite. In addition, experimental tree shrews displayed a significantly longer latency to enter the SI zone in the second 15 min session(targetpresent) than in the first 15 min session(targetabsent), which was different from that found in mice.Distinct behavioral patterns in response to a conspecific male were also observed in male tree shrews and mice in the first, second, and third 5 min periods. Thus, social behaviors in tree shrews and mice appeared to be time dependent. In summary,our study provides results of a modified social preference-avoidance test designed for the assessment of social behavior in tree shrews. Our findings demonstrate the existence of social avoidance behavior in male tree shrews and prosocial behavior in male mice toward unfamiliar conspecifics. The tree shrew may be a new animal model, which differs from mice, for the study of social avoidance and prosocial behaviors.

Pathogenesis of chronic social defeat stress model induced depressive-like mouse model according to LC-MS/MS-based metabolomics

OBJECTIVE To explore the pathogenesis of depression according to the LC-MS/MS-based metabolomics in the mouse model which exhibits social avoidance state induced by the chronic social defeat stress model(CSDS).METHODS Twenty male C57BL/6N mice were randomly divided into control group and model group suffering CSDS,and the ICR retired breeder mice were used to attack the model group for 14 d of chronic social defeated stress.The open field test and source preference test were both used to observe depression-like behavior.Besides,the social interaction test is used to observe the social interaction state,especially.After the stress,the serum samples of mice were collected,and the changes of endogenous metabolites were analyzed by LC-MS metabolomics technology,and the pathway analysis of the differential metabolites was performed to explore the pathogenesis of the CSDS induced depressive-like mouse model.RESULTS After the stress of CSDS was completed,the mice in the model group showed a significant slowdown in body weight growth,a reduction in the source preference rate,and a significant reduction in the total distance and the number of rearing in the open field test.Distinctively,the social interaction rate is remarkably decreasing.There are 24 differential metabolites found in the serum of CSDS model mice.CONCLUSION The mouse who suffered CSDS stress would show depressive-like behavior.Based on the LC-MS/MS metabolomics,24 differential metabolites were found in the serum of CSDS model mice.The amino acid metabolism might be significant to the pathogenesis of the CSDS induced depressive-like mouse model.

高功能孤独症儿童的统合型房树人绘画测验特征

目的:探讨高功能孤独症儿童的统合型房树人(S-HTP)绘画测验特征及其社会性发展。方法:对符合美国精神障碍诊断与统计手册第4版(Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition,DSM-Ⅳ)的35例高功能孤独症儿童和年龄、性别、智商相匹配的70例正常对照儿童进行S-HTP绘画测验,分析高功能孤独症儿童S-HTP绘画测验特征(整体评价15个项目、房屋评价9个项目、树木评价5个项目和人物评价14个项目)。结果:在S-HTP绘画测验中,高功能孤独症儿童绘画特征与正常儿童存在明显差异。在主要反映社交互动水平的整体评价中有8个项目存在差异,如孤独症患儿绘画的画面统合性强的比例明显低于正常儿童[5.7%(2/35)vs.67.1%(47/70),P<0.05];在主要反映家庭关系的房屋评价中的有4个项目存在差异,如孤独症儿童绘画中人只在房屋外面的比例明显高于正常儿童[100%(35/35)vs.85.7%(60/70),P<0.05];在主要反映无意识的自我形象的树木评价中有4个项目存在差异,如孤独症儿童树木简化的比例明显高于正常儿童[73.5%(25/35)vs.24.3%(17/70),P<0.05];在主要反映有意识的自我形象和人际关系的人物评价中有8个项目存在差异,如孤独症儿童绘画人物数目2人以上的比例明显低于正常儿童[20.0%(7/35)vs.68.6%(48/70),P<0.05]。结论:高功能孤独症儿童统合型房树人绘画测验绘画特征反映出其社会性发展落后于正常同龄儿童,主要表现在社交互动、人际关系、自我概念和家庭关系方面。

棕色田鼠幼仔对父鼠的早期识别及条件位置偏爱

群居性动物的幼仔对亲本的识别有利于获得最大化的亲本抚育。雄性棕色田鼠对幼仔具有较高水平的父本投资,那么幼仔在断乳前是否能够识别父鼠并形成条件位置偏爱(Conditioned place preference,CPP)呢?本研究通过双向选择测试、社会互作测试以及CPP测试探讨了这一问题。双向选择结果显示,与陌生雄鼠相比,出生后14d和21d的幼仔对父鼠访问的持续时间及潜伏期有显著性差异(P<0.05);社会互作结果表明,14d幼仔对父鼠的跟随行为较陌生雄鼠多,但探究行为及亲密行为没有显著性差异(P>0.05),21d幼仔对父鼠的探究行为较少、跟随行为和亲密行为较多(P<0.05)。CPP结果表明,在连续4d(出生后13～16d;19～22d)的父鼠强化后,第17d和第23d的幼仔不能形成对父鼠的位置偏爱(P>0.05)。这些结果说明断乳前的棕色田鼠幼仔已能够识别父鼠和陌生雄鼠,但不能形成对父鼠的位置偏爱。

钩吻素子对孤立大鼠的抗焦虑作用及其机制

目的研究钩吻素子连续皮下给药对孤立大鼠抗焦虑样行为的影响,并探讨其作用机制。方法 Wistar大鼠单笼饲养18 d,第12天开始每天皮下注射钩吻素子0.5、1.5 mg/kg 1次,连续给药7 d。孤立饲养第17天(即给药第6天)进行高架十字迷宫试验,试验最后1 d(即给药第7天)进行自主活动试验和群居接触试验。行为学试验结束后,通过酶联免疫吸附测定(ELISA)检测动物血浆中促肾上腺皮质激素(ACTH)和皮质酮浓度,并测定海马中孕酮和别孕烯醇酮的含量。结果钩吻素子连续给药6 d能有效提高孤立大鼠在高架十字迷宫开臂区的活动情况,提示钩吻素子具有抗焦虑作用;钩吻素子连续给药7 d对大鼠自主活动无影响,但能提高配对孤立大鼠的接触次数和接触时间,进一步证明了钩吻素子的抗焦虑效应。与模型组比较,钩吻素子1.5 mg/kg治疗组能降低孤立大鼠血浆中的皮质酮水平(P<0.05),钩吻素子0.5、1.5 mg/kg治疗组均能提高大鼠海马中的别孕烯醇酮含量(P<0.01);而各组动物血浆中的ACTH浓度和海马中的孕酮含量则未见变化。结论钩吻素子连续给药能增加孤立大鼠的抗焦虑样行为,其抗焦虑作用可能与调节大鼠海马的别孕烯醇酮含量和抑制下丘脑-垂体-肾上腺轴异常活动有关。

利用斑马鱼成鱼建立致幻类化合物行为评价模型

目的利用斑马鱼这一新型模式动物,建立致幻类化合物成鱼行为测试模型,并考察模型有效性。方法利用斑马鱼行为视频跟踪分析系统自动记录动物行为参数,以栖底性、镜像反射及社会交互行为作为评测指标,采用甲基苯丙胺浓度2 mg·L-1、氯胺酮浓度20 mg·L-1,分别急性暴露30 min后进行行为测试。结果与正常组相比,在成鱼自发活动方面,甲基苯丙胺与氯胺酮急性暴露对斑马鱼的运动距离无明显影响,而使垂直方向的穿越次数明显下降;在镜像反射方面,给予不同化合物均使斑马鱼在中央区的停留时间明显增加,且在镜像区的高活动性比例明显上升,提示化合物改变了鱼对镜像区的偏爱,并在给定浓度下使鱼具有一定攻击性;急性给予两种化合物均明显降低鱼之间相互接近的持续时间,表明成鱼社会交互行为受到抑制。结论所建立的斑马鱼行为模型对于致幻性非常敏感,且在行为表现上具有特征性。

白芍总苷对母婴分离小鼠行为学与相关脑区小胶质细胞的影响

目的:通过观察行为学与相关脑区小胶质细胞标志物离子钙接头蛋白(ionized calcium-binding adaptor molecule,Iba)-1的表达情况,探讨白芍总苷(total glucosides of paeony,TGP)对母婴分离小鼠的影响。方法:选用出生后经过连续10 d、每天8 h母婴分离的成年C57BL/6J雄性小鼠作为研究对象,以TGP进行4周的干预,通过旷场自由活动及社会交互行为实验观察行为模式变化,运用免疫组织化学方法检测海马与下丘脑脑区Iba-1蛋白表达,观察小胶质细胞功能状态的变化。结果:TGP可显著缩短母婴分离小鼠的旷场活动总运动距离(P<0.05),显著缩短社会交互行为中的训练探查时间和辨别探查时间(P<0.05),显著降低Iba-1在海马CA1区、海马CA3区、下丘脑的表达(P<0.01)。结论:TGP可明显改善母婴分离小鼠的行为模式变化,抑制小胶质细胞功能的活化,可能为其调节母婴分离小鼠成年后抑郁样行为的作用机制之一。

慢性社会应激模型的构建及其对雄鼠生殖健康影响的研究

目的构建慢性社会应激模型,探究慢性社会应激对雄性C57BL/6小鼠生殖健康的影响。方法将C57BL/6小鼠分成应激组和对照组;应激组予以慢性社会应激25d后,通过社会交互作用的行为学实验和体质量变化评估应激模型的构建状况,并对比两组小鼠生殖腺质量、精子计数等指标评估生殖健康的影响。结果慢性社会应激结束后,通过社会交互作用的行为学实验,发现应激组小鼠在行为上具有明显社会逃避行为;同对照组相比应激组小鼠生殖腺质量、精子数目均明显降低。结论慢性社会应激可以损伤雄鼠生殖功能,主要表现在生殖腺萎缩、精子数目减少等。

配对(组)口语测试的社会性及其微观研究

受交际语言教学、批判语言学、社会语言学的影响,批判语言测试(Critical Language Testing)提出把语言测试置于更广阔的社会政治语境中,开始重视对语言测试的社会维度即测试的社会性以及测试带来的社会影响的研究。配对(组)口语测试是当今国内外口语测试中较为广泛应用的测试形式,具有鲜明的社会性。研究发现考生在考试过程中的表现和最后得分与诸多社会因素相关。本文着重分析配对(组)口语测试的社会性及其研究方法和现状,提出了今后配对(组)口语测试社会性研究的方向。

丁螺环酮对地西泮抗焦虑作用的影响

应用大鼠 Vogel冲突饮水实验和群居接触焦虑模型 ,观察丁螺环酮 (Bus)对地西泮抗焦虑作用的影响 .结果发现 ,以低于有效剂量的 Bus与低于有效剂量的地西泮合用 ,能显著促进大鼠的抗冲突饮水次数和群居接触时间 .而以低于有效剂量的Bus与有效剂量的地西泮合用 ,则能使地西泮的抗焦虑作用消失 .结果表明 ,Bus在不同条件下能加强或减弱地西泮的抗焦虑作用 ,提示中枢 5- HT与γ-氨基丁酸 -苯二氮艹卓 系统之间存在着相互作用 ,并可能共轭调节焦虑的病理生理过程 .

社会互动对农民工环境行为的影响机制

基于CGSS2013全国数据,运用Bootstrap中介检验法,实证分析环境知识和环境风险感知在农民工社会互动影响环境行为中的多重中介作用。研究结果表明,社会互动对农民工环境行为有着显著影响,同时也通过环境知识、环境风险感知、环境知识—环境风险感知三条中介路径正向间接影响农民工环境行为,其中,环境知识的影响中介效应相对最大。鉴于此,应激发社会互动在环保中的潜力,大力打造新型信息传递载体,引导农民工的环保行为。

Assessment of Cognitive skills via Human-robot Interaction and Cloud Computing

Technological advances are increasing the range of applications for artificial intelligence, especially through its embodiment within humanoid robotics platforms. This promotes the development of novel systems for automated screening of neurological conditions to assist the clinical practitioners in the detection of early signs of mild cognitive impairments. This article presents the implementation and the experimental validation of the first robotic system for cognitive assessment, based on one of the most popular platforms for social robotics, Softbank "Pepper", which administers and records a set of multi-modal interactive tasks to engage the user cognitive abilities. The robot intelligence is programmed using the state-of-the-art IBM Watson AI Cloud services, which provide the necessary capabilities for improving the social interaction and scoring the tests. The system has been tested by healthy adults (N= 35) and we found a significant correlation between the automated scoring and one of the most widely used Paper-and-Pencil tests. We conclude that the system can be considered as a screening instrument for cognitive assessment.

专业类型在特里尔社会应激影响风险决策中的调节作用

目的:探讨专业类型在特里尔社会应激影响风险决策中的调节作用。方法:62大学生分为应激组(n=30)和对照组(n=32),应激组采用特里尔社会应激测试(TSST)诱发急性心理应激感,对照组不做处理,2组大学生分别完成仿真气球模拟任务(BART)作为测试风险决策行为的指标;比较2组大学生风险决策行为得分,分析专业类型与组别的交互作用在风险决策行为上的差异。结果:应激组大学生的风险决策行为得分高于对照组,差异有统计学意义(t=2.44,P<0.05);不同组别与专业类型学生风险决策行为的交互作用显著(F=3.83,P<0.05),交互作用的简单效应分析结果显示,应激组中理科学生风险寻求上的得分高于文科学生(F=11.59,P<0.05),对照组中文科与理科学生风险寻求上的得分差异无统计学意义(F=0.540,P=0.586)。结论:急性心理应激能激发大学生个体更愿意选择冒险的倾向,但受到专业类型的调节。

Behavioral Characteristics of Pharmacologically Selected Lines of Rats: Relevance to Depression

This brief review discusses the behavioral consequences of two pharmacologically selected lines of rats. Flinders Sensitive (FSL) and Flinders Resistant (FRL) Lines of rats were selected on the basis of differential hypothermic and behavioral responses to the anticholinesterase, diisopropylfluorophosphate (DFP). FSL rats are more sensitive to the hypothermic effects of cholinergic, serotonergic, and dopaminergic agonists but less sensitive to the locomotor or stereotypic effects of dopamine agonists. FSL rats exhibit greater immobility in the forced swim test and reduced social interaction compared with FRL rats, but do not differ in saccharin intake, behavior in the elevated plus maze, or responses for rewarding brain self-stimulation. The exaggerated immobility and reduced social interaction are counteracted by chronic treatment with antidepressants. Because FSL rats were more sensitive to 5-HT1A receptor agonists, high (HDS) and low (LDS) 8-OH-DPATsensitive lines were selectively bred for differential hypothermic responses to the 5-HT1A receptor agonist, 8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT). HDS rats were also more sensitive to the hypothermic effects of oxotremorine, a cholinergic agonist, but selection for this response did not diverge with later selection. HDS rats exhibited greater immobility in the forced swim test than LDS rats and this correlated response could be seen early in selection (generation 3). HDS rats also showed reduced social interaction compared to LDS rats, but did not differ in behavior in the elevated plus maze. These findings confirm that selection for hypothermic responses to pharmacological agents do have behavioral consequences, notably the production of depressive-like phenotypes, which can be counteracted by chronic antidepressant treatment. Because increased 5-HT1A receptor sensitivity was common to both selected lines (FSL and HDS), neurobiological processes dependent on this receptor could contribute to the abnormal behaviors that manifest in these rat lines and thus suggesting a mechanism underlying depressive behaviors in humans. However, available human data are inconsistent with this hypothesis and suggest that other mechanisms underlie these behavioral abnormalities in HDS and FSL rats. These mechanisms as well as additional behavioral testing in these rat lines will be discussed.

小鼠三箱社交偏好测试影响因素追溯分析

目的:探究多种因素对三箱社交偏好(TCSP)测试的影响。方法:追溯297只健康雌雄C57/BL6小鼠的原始实验数据,按性别、年龄、实验装置、行为实验室、动物饲养室、季节因素各自分组进行三箱社交偏好测试。结果:对三箱社交偏好测试单因素分析结果显示,性别、年龄、实验装置、行为实验室、动物饲养室、季节均未显著影响三箱社交实验结果;对三箱社交行为测试多元线性回归分析结果显示,性别、年龄、实验装置、行为实验室、动物饲养室、季节亦均不能显著影响三箱社交实验结果。结论:性别、年龄、实验装置、行为实验室、动物饲养室和季节因素均未显著影响三箱社交实验的结果,表明三箱社交实验可以稳定准确地评价小鼠社交行为的偏好状态。

Spatial Structure of Peer Networks and Academic Achievement Based on a Random Control Trial Experiment

This paper investigates whether changing the seating arrangement in a classroom can facilitate positive spillovers from top-performing students to others,using a field experiment conducted in a Chinese high school.Among study groups with balanced abilities,the treatment altered the spatial distribution by assigning the two top students to seats in the spatial center of each group.In the reference groups where students were allowed to choose their own seating arrangements,the lowest performing were significantly less likely to sit next to a top student than they would be under a random assignment.The results suggest that,in the treated groups,there could be enhanced academic spillovers from the top students.The treatment especially benefited the two lowest performing students in science subjects.In contrast,the treatment exerted negative effects on the test scores of the two middle-performing students,due to a disruption mechanism.The results suggest that the spatial layout of a peer network can have a significant impact on learning outcomes.

负性情绪应激通过上调白介素-6水平导致小鼠酒精摄入增多

目的 探究负面情绪与小鼠酒精消耗之间的关系以及其分子机制。方法 将8周龄野生型C57BL/6J小鼠进行慢性社交挫败实验,通过社交互动评分分组:易感组(即表现出明显负性情绪)和抵抗组(未表现出明显负性情绪),之后进行糖水偏好实验再次验证负面情绪动物模型是否成功,最后观察各组小鼠酒精消耗量以及检测小鼠不同脑区白介素-6(Interleukin-6,IL-6)水平;将压力易感组的8周龄野生型C57BL/6J小鼠(即具有负面情绪小鼠)分成2组,1组腹腔注射Anti-IL-6抗体,另1组注射Anti-IgG,比较2组酒精消耗量。结果 行为学实验发现,相对于对照组和抵抗组,易感组中小鼠的酒精摄入增多(P<0.01);分子生物学实验发现,与对照组和抵抗组比较,易感组小鼠大脑IL-6水平均明显升高(P<0.05或0.01),且IL-6水平升高与酒精消耗的增多呈正比;易感组小鼠注射Anti-IL-6抗体后其酒精消耗明显减少(P<0.05)。结论 IL-6参与负面情绪导致的小鼠酒精摄入增多,使用抗体降低IL-6水平可减少负性情绪所致的酒精摄入增多。

基于交互观的口语互动能力构念界定

传统二语能力构念的界定着重从个体认知角度描述语言使用者内在的语言能力,但是随着学界越来越重视语言的社会属性和功能,不少学者提出构念定义应该更多考虑社会互动和语境对语言使用的影响。因此,本文提出基于交互构念理论构建口语互动能力构念描述框架的初步设想,旨在使口语测试更加充分地体现真实口语交际的特点和口语交际能力的本质。

社会互动与家庭创业行为

如何激发"双创"活力是实现"大众创业、万众创新"的关键。文章基于最新的2016年中国家庭追踪调查(CFPS)微观数据,采用离散选择模型和OLS模型,分析了社会互动对家庭创业决策的影响,并对其机制进行了初探。结果表明,社会互动的三个代理变量,即人情礼金支出、通讯支出及非家庭成员间聚餐支出均对家庭创业决策产生了积极影响。具体而言,在其他变量既定的情况下,人情礼金支出、通讯支出和非家庭成员间聚餐支出每提高一个单位,将使家庭创业的几率增加1.7%、3.7%和3.5%。在考虑了潜在的内生性后,本文所得结论依然成立。影响机制研究表明,社会互动通过信息获取和社会性学习机制、相对财富关注机制及缓解创业融资约束而对家庭创业决策产生影响。进一步研究发现,随着互联网的发展,网络信息会对社会互动产生一定的替代,但替代效应并不显著。文章的研究为激发"双创"活力提供了一个新的政策视角,相关部门在制定涉及个体家庭创业的政策时,应充分考虑社会互动的作用。