Poly I:C母体免疫刺激诱导的子代精神分裂症神经发育动物模型

精神分裂症是一组病因未明的重性精神障碍,其病理生理学机制极其复杂,建立能够确切模拟精神分裂症的动物模型对于其发病机制的研究及抗精神分裂症药物的研发具有十分重要的意义。本文意在介绍产前母体免疫刺激(聚肌胞苷酸聚肌苷酸-聚胞苷酸,Poly I:C)诱导子代出现精神分裂症样的神经发育动物模型,以及该模型对精神分裂症的病因研究、生物学机制及其治疗和药物研发的重要意义。     

精神分裂症的潜伏抑制动物模型

精神分裂症动物模型的建立,是当前研究精神分裂症的神经生物学机制以及开发新的抗精神病药物的一个重要课题。文章系统地阐述了以潜伏抑制为行为模式的精神分裂症动物模型的理论以及神经机制,并重点介绍了精神分裂症的潜伏抑制动物模型的建立方法,包括（1）调节某些与精神分裂症相关的中枢神经递质的传递活动;（2）对与精神分裂症有关的中脑-伏隔核神经环路进行结构损伤或药物性干预;（3）在发育早期给予免疫刺激或环境应激     

对听感觉运动门控自上而下调节的动物模型和神经机制

对惊反射的前脉冲抑制是减少干扰影响、保护脑内信息加工的重要机制。它既是研究感觉运动门控的模型, 也是探究精神分裂症机制的模型。前脉冲抑制可被选择性注意和情绪等高级认知活动所调节。本论文工作围绕着恐惧条件化和知觉空间分离去掩蔽(空间选择性注意)对听觉前脉冲抑制多层次化的自上而下调节, 在大鼠行为模型、神经通路、神经电生理机制等几个层次上开展了系统性研究, 并引入了精神分裂症的神经发育模型, 证实早期社会隔离饲养对前脉冲抑制注意调节的破坏影响。本论文研究成果不仅对认识正常情况下脑在复杂刺激场景中的信息加工机制有重要意义, 以感觉运动门控认知调节功能缺失为基础的动物模型也将推动精神分裂症心理学和神经生物学机制的研究。     

对中医实验动物模型的思考

众所周知 ,动物模型的研制对医学发展有着重要的意义。综观现代医学的发展 ,很大程度上取决于疾病动物模型的进展情况。实验动物模型对中医事业的发展同样取得了较大的成就 ,动物模型在中医科研中的作用已成为整个中医界的共识。然而 ,从目前中医动物模型的研究结果来看 ,对中医理论的发展远未起到显著的作用。因此 ,我们有必要对中医实验动物模型的研究进行更深入的探讨与思考。1　中医病因的辨证理解问题在目前许多疾病的动物模型复制研究中 ,多是按中医病因进行 ,其理论依据来自一些中医经典原文。但由于中医病因学内容的形成和发展受当…     

动物模型蛋白质组学技术在高血压疾病的研究进展

蛋白质组学是研究细胞内全部蛋白质的组成及其活动规律的科学,蛋白质组学研究不但能揭示病因不明疾病的发生和发展机制,并为提供新的诊断技术、治疗方法和药物靶点等有积极的作用。因高血压的病因还不十分清楚,人们希望用分子生物学揭示其神秘的面纱,因此蛋白质组学与高血压的研究,成为高血压模型动物及其临床领域研究的热点,本文对动物模型蛋白质组学技术在高血压疾病的研究进展情况进行综述。     

对精神分裂症病因中心理因素的分析和药物配合心理综合治疗对防复发的作用(附84例防复发实践总结)

现代精神病学对精神分裂症病因的研究中,除了遗传因素之外,愈来愈关注心理因素对发病的重要作用。本文总结从1979年9月至1981年6月在本市鼓楼区建立家庭病床,对84例治愈或基本治愈出院的精神分裂症患者采用药物配合心理综合治疗预防和减少复发的实践体会报告如下。资料选择:随机取出鼓楼区治愈或基本治愈出院的精神分裂症84例,作为家庭治疗对     

执行功能与精神分裂症

执行功能障碍是精神分裂症最重要的认知功能障碍,与精神分裂症其它方面的障碍有着密不可分的关系。文章在相关的认知神经心理学和临床研究的基础上,分别综述了精神分裂症执行功能障碍的特点、研究方法、相关脑机制,执行功能与注意、记忆等一般认知功能间的关系,执行功能与精神症状间的联系及其在诊断、康复、判断预后方面的作用等。对精神分裂症执行功能障碍的认识有助于更深入地理解其病因机制,并有利于临床评价与防治     

母婴分离的动物模型及其神经生物学机制

利用社会环境剥夺建立的精神分裂症动物模型,是当前研究精神分裂症神经生物学机制的一个热点课题.作为一种重要的早期社会剥夺方式,出生后至断乳前的母婴分离日益受到关注.文章综合阐述了母婴分离对啮齿类动物行为及神经发育影响的最新研究成果,表明母婴分离可以部分模拟精神分裂症的行为及中枢表现,证实了该模型的可行性;并进一步分析了影响实验结果的各种相关因素,为今后采用该模型进行深入研究提供一定的理论支持.     

创伤后应激障碍的组蛋白修饰机制

创伤后应激障碍是一种具有复杂病因学的精神疾病, 多发生于个体受到重大创伤事件后。创伤后应激障碍的发生发展过程受到环境和遗传易感性的共同作用, 存在着较大的个体差异; 而表观遗传学作为一门研究多变环境因素调控基因表达的可遗传变化的学科, 近年来在创伤后应激障碍的研究中受到越来越多的重视。表观遗传机制之一——组蛋白修饰机制在创伤后应激障碍的发生中起着重要作用, 并且由于组蛋白修饰可以受到多种酶的调控, 其灵活的可逆化和精细调控为相应的药物研发提供了可能性和便利。因此, 深入探讨创伤后应激障碍的组蛋白修饰机制, 对于相关疾病的临床治疗及药物研发具有十分重要的意义。当前创伤后应激障碍的组蛋白修饰研究主要使用动物模型, 临床研究较少; 组蛋白的类型则主要关注组蛋白H3和H4乙酰化; 此外, 同以往的研究结果一致, 组蛋白修饰水平的变化主要发生在前额叶、海马体和杏仁核区域, 参与免疫系统、血清素系统和神经肽Y能系统等相关通路的调节。当前PTSD组蛋白修饰的研究结果间还存在较大的异质性, 未来的研究应采用更加一致和实用的分析和报道方法, 以最大限度地发挥研究的影响。     

对胃肠动力起搏机制中存在问题的思考

胃肠动力障碍性疾病现在呈现迅速增长的趋势,然而针对目前的作用机制而研发的药物在临床应用中产生了显著的矛盾,尤其是目前的公认的两种理论存在着明显的矛盾。故此进一步针对矛盾问题的研究具有十分重要的意义。     

Neurodevelopmental influences in the genesis and epigenesis of schizophrenia: An overview

The classical view of schizophrenia as a dementing disorder has recently been challenged by several findings pointing to a prenatal/perinatal origin of at least some of the brain abnormalities seen in these patients. This article reviews evidence from a number of different fields, including postmortem neuropathology, in vivo neuroimaging, developmental neuropsychology, and obstetric epidemiology in assessing the viability of a neurodevelopmental perspective of schizophrenia. Although the case for viewing schizophrenia as a neurodevelopmental condition is still circumstantial, and several gaps in this model remain, evidence from these diverse lines of inquiry converge to indicate at least a partial role of disturbances of brain development in the disorder's genesis and epigenesis.     

Neurodevelopmental influences in the genesis and epigenesis of schizophrenia: An overview

The classical view of schizophrenia as a dementing disorder has recently been challenged by several findings pointing to a prenatal/perinatal origin of at least some of the brain abnormalities seen in these patients. This article reviews evidence from a number of different fields, including postmortem neuropathology, in vivo neuroimaging, developmental neuropsychology, and obstetric epidemiology in assessing the viability of a neurodevelopmental perspective of schizophrenia. Although the case for viewing schizophrenia as a neurodevelopmental condition is still circumstantial, and several gaps in this model remain, evidence from these diverse lines of inquiry converge to indicate at least a partial role of disturbances of brain development in the disorder's genesis and epigenesis.     

Infectious and immune factors in the pathogenesis of neurodevelopmental disorders: epidemiology, hypotheses, and animal models

Both genetic and environmental factors contribute to the pathogenesis of a wide variety of neurodevelopmental disorders, including autism, mental retardation, and schizophrenia. Some heritable disorders approach 100% penetrance; nonetheless, even in these disorders, subtle aspects of clinical disease expression may be influenced by the environment. In other disorders with genetic influences, exogenous factors, and the timepoint(s) during nervous system development at which they are introduced, modulate expression of disease. Elucidation of the mechanisms guiding this intricate interplay between host response genes, environmental agents, and the neurodevelopmental context within which these interactions occur, is necessary to understand the continuum of clinical outcomes. This chapter will review the evidence that infectious and immune factors may contribute to the pathogenesis of neurodevelopmental disorders, describe an animal model of neurodevelopmental disorders based upon viral infection, identify processes by which neural circuitry may be compromised, and outline areas for future research.     

Sex differences in prenatal epigenetic programming of stress pathways

Maternal stress experience is associated with neurodevelopmental disorders including schizophrenia and autism. Recent studies have examined mechanisms by which changes in the maternal milieu may be transmitted to the developing embryo and potentially translated into programming of the epigenome. Animal models of prenatal stress have identified important sex- and temporal-specific effects on offspring stress responsivity. As dysregulation of stress pathways is a common feature in most neuropsychiatric diseases, molecular and epigenetic analyses at the maternal-embryo interface, especially in the placenta, may provide unique insight into identifying much-needed predictive biomarkers. In addition, as most neurodevelopmental disorders present with a sex bias, examination of sex differences in the inheritance of phenotypic outcomes may pinpoint gene targets and specific windows of vulnerability in neurodevelopment, which have been disrupted. This review discusses the association and possible contributing mechanisms of prenatal stress in programming offspring stress pathway dysregulation and the importance of sex.     

Schizophrenia: A Neurodevelopmental Perspective

Diverse lines of research suggest that schizophrenia is a genetically influenced neurodevelopmental disorder. Family, twin, and adoption studies suggest that most cases of schizophrenia involve a genetic diathesis that is necessary but not sufficient for development of the disorder. Histological, neuroimaging, and neuropsychological findings converge in providing evidence for medial-temporal and frontal lobe dysfunction that likely predates the onset of psychosis. Behavioral phenomenology and neurobiology suggest that dopamine plays a crucial moderating role between these structural abnormalities and functional impairment. Recently, investigators have used animal models and clinical syndromes to integrate these findings into neurodevelopmental models of schizophrenia that hold great potential for yielding etiological insight.     

Sexual orientation and handedness in men and women: a meta-analysis

Recent findings suggest that sexual orientation has an early neurodevelopmental basis. Handedness, a behavioral marker of early neurodevelopment, has been associated with sexual orientation in some studies but not in others. The authors conducted a meta-analysis of 20 studies that compared the rates of non-right-handedness in 6,987 homosexual (6,182 men and 805 women) and 16,423 heterosexual (14,808 men and 1,615 women) participants. Homosexual participants had 39% greater odds of being non-right-handed. The corresponding values for homosexual men (20 contrasts) and women (9 contrasts) were 34% and 91%, respectively. The results support the notion that sexual orientation in some men and women has an early neurodevelopmental basis, but the factors responsible for the handedness-sexual orientation association require elucidation. The authors discuss 3 possibilities: cerebral laterality and prenatal exposure to sex hormones, maternal immunological reactions to the fetus, and developmental instability.     

Mental disorders,brain disorders,neurodevelopmental disorders: challenges for the philosophy of psychopathology after DSM-5

The publication of DSM-5 has been accompanied by a fair amount of controversy. Amongst DSM's most vocal ‘insider’ critics has been Thomas Insel, Director of the US National Institute of Mental Health. Insel has publicly criticised DSM's adherence to a symptom-based classification of mental disorder, and used the weight of the NIMH to back a rival research strategy aimed at a more biology-based diagnostic classification. This strategy is part of Insel's vision of a future, more preventative psychiatry in which mental disorders are not only understood as biological disorders of the brain, but also as neurodevelopmental disorders. This paper examines the interest and merit of Insel's views of mental and neurodevelopmental disorder for the philosophy of psychopathology, with a special focus of his neurodevelopmental model of schizophrenia. Pitman's ‘moderate materialism’ will be used both as a philosophical lens through which to examine Insel's position, as well as an example of a philosophical framework that may require updating and revision in the light of moves towards a neurodevelopmental conception of mental disorder.     

Early maternal deprivation retards neurodevelopment in Wistar rats

A single 24 h period of maternal deprivation (MD) in rats has been shown to induce, in adulthood, a number of abnormalities in brain and behaviour that also occur in patients with schizophrenia. However, the short-term behavioural effects of MD have not been studied in detail. Since patients with schizophrenia are characterized by a retardation of normal development, we aimed in the present study to investigate the development of control rats and rats that were exposed to MD on postnatal day 9. Compared to control animals, MD rats showed (1) a reduction in body weight, (2) an increased in reversal latency in negative geotaxis, (3) a delayed eye opening, (4) a delayed emergence of walking and rearing; and (5) a delayed emergence of the behavioural response to amphetamine (amph). On the other hand, MD and control rats responded similarly to the non-competitive NMDA antagonist MK801. These data clearly show that early MD delays development, especially of the dopaminergic system and confirm our hypothesis that MD may represent an interesting animal model for the neurodevelopmental hypothesis of schizophrenia.     

Reorganization of equivalence classes: effects of preliminary training and meaningful stimuli

In Condition 1, adults learned the baseline relations for the three equivalence classes A1‐B1‐C1‐D1‐E1, A2‐B2‐C2‐D2‐E2, and A3‐B3‐C3‐D3‐E3. Classes contained abstract shapes in the ABS and four preliminary training groups. Each class in the PIC group contained one picture and four abstract shapes. Before class formation for four other groups, preliminary training involved establishing identity (CC) or arbitrary (CX) relations either with or without a delay. Without preliminary training, classes formed with low and high likelihoods in the ABS and PIC groups, respectively. Preliminary training with no delay produced modest increases in class formation, while preliminary training with delay produced large increases in class formation. Condition 2 replicated Condition 1 but with training of reassigned BC and CD relations that linked C from one class to B and D from another class: B1‐C2, B2‐C3, B3‐C1, C2‐D1, C3‐D2, and C1‐D3. Subsequent tests assessed the emergence of the reorganized classes A1‐B1 ‐C2 ‐D1‐E1, A2‐B2‐ C3 ‐D2‐E2, and A3‐B3‐ C1 ‐D3‐E3. All preliminary training procedures increased likelihood of forming the reorganized classes to the level seen in the PIC group. Greater gains were produced by preliminary training with no delays than with delays. Test performances also showed how preliminary training influenced baseline acquisition speed and participant‐defined relations.     

A neurodevelopmental perspective on male violence

Research is increasingly documenting a neurobiological basis to violence. This review takes a neurodevelopmental perspective on the very small group of males who grow up to become persistent violent offenders. After outlining six criteria for what constitutes a neurodevelopmental disorder, the extent to which chronic violence meets these definitional criteria is examined, covering the fields of genetics, structural and functional brain imaging, and neuropsychology. Early health risk factors for violence are then outlined, including birth complications, minor physical anomalies, prenatal smoking and alcohol exposure, poor nutrition, lead exposure, and traumatic brain injury. Persistent adult violence is argued to originate in aberrant temperamental behavior in early childhood, to have a stable developmental trajectory, and to be associated with impaired education, social, and occupational functioning. Taken together, it is argued that chronic adult violence meets criterion for being conceptualized as having neurodevelopmental origins and that an important, but not sole, source of neural maldevelopment lies in prenatal and early postnatal risk factors. This review concludes with a recognition of the sociopolitical context within which a neurodevelopmental perspective on chronic violence sits, together with directions for future research, including whether a neurodevelopmental hypothesis is best applied to reactive as opposed to proactive aggression.