精神分裂症神经发育动物模型的研究进展

Progress in the research of neurodevelopmental animal models of schizophrenia

目的:精神分裂症是一种极其严重的精神疾病,目前对其病因尚无明确的认识。精神分裂症的神经发育假说强调早年的干扰经历对日后病发的影响,近年来受到研究者的普遍关注。在这一领域,动物模型的研究发展较快,提供了大量的支持证据。本文对精神分裂症神经发育动物模型的研究进行小结,考察不同模型之间的联系并对其内在的生理机制加以分析。资料来源:应用计算机检索Medline数据库1991-01/2006-01期间的关于精神分裂症神经发育动物模型研究的文章,检索词“schizophrenia,neurodevelopment,animalmodel”,限定文章语言种类为English。同时通过图书馆手工查阅相关精神分裂症方面的资料。资料选择:对资料进行初审,纳入标准:①与精神分裂症神经发育机制相关的动物行为、神经生化和心理药理学的研究。②对精神分裂症动物模型的综述性研究。排除重复性研究。资料提炼:共收集到符合上述要求的文献38篇,排除5篇重复性研究,纳入33篇,其中4篇为综述性研究,其余为实验研究。资料综合:精神分裂症动物模型研究的基础是行为模型,主要包括前脉冲抑制、潜伏抑制以及颠倒学习3种。精神分裂症的神经发育动物模型包括早期海马损伤、隔离饲养和母婴分离3类,经过早期干预的动物成年后表现出前脉冲抑制缺失、潜伏抑制缺失、颠倒学习能力降低以及社会行为减少等行为,并出现对多巴胺兴奋剂的过度反应以及对多巴胺拮抗剂反应性的降低。上述障碍涉及不同脑区的损伤和中枢神经递质的失调,其中,海马多巴胺能、去甲肾上腺素能系统等的紊乱可能是主要影响机制。结论:神经发育早期干预手段可以造成动物成年以后的行为异常和多巴胺系统功能紊乱,海马腹侧区的结构以及功能障碍可能是其中的关键因素。

OBJECTIVE： Schizophrenia is one of most serious mental disorder. There are still no consistent conclusions on its etiology. The neurodevelopmental hypothesis, which emphasizes the effect of early disturbance on consequent pathologic symptoms, has received intensive attention recently. Research on animal models has provided large amounts of evidence to support this hypothesis. This review aims at summarizing and comparing different neurodevelopmental animal models of schizophrenia, and analyzing the physiological mechanisms associated with the models. DATA SOURCES： An online search of Medline was undertaken to identify English articles about neurodevelopmental animal models of schizophrenia published from January 1991 to January 2006 by using the keywords of ＂schizophrenia, neurodevelopment, animal model＂. Meanwhile, relevant information was also searched manually in libraries. STUDY SELECTION： Primary check-up was conducted, and the inclusion criteria were： ①researches on behavior, neurochemical and psychopharmacological neurodevelopmental mechanisms.②Reviews on animal models of schizophrenia. Exclusion criteria： repetitive researches. DATA EXTRACTION： An total of 38 articles were in accordance with the above criteria, among which 5 repetitive references were excluded, and 33 were involved. Among those selected articles, 4 were reviews, and others were experimental studies, DATA SYNTHESIS： Research on animal models of schizophrenia was based on the behavior of models, such as pre-pulse inhibition, latent inhibition and reversal learning. The neurodevelopmental animal models of schizophrenia included neonatal hippocampus lesion, isolated rearing and maternal deprivation. After early intervention, animals showed pre-pulse inhibition loss, latent inhibition missing, impaired reversal learning and less behaviors as well as over activity to dopamine agonists and less activity to dopamine antagonists. Those deficiencies involved impairments at different brain areas and malfunction of central neurotransmitter systems, in which hippocampal dopaminergic and uoradrenergic system turbulence might play a key role. CONCLUSION： Early neurodevelopmental interventions result in abnormal behavior and malfunction of dopamine system in adult animals. Strucrural and functional abnormities of the ventral hippocampus may be the major factors of the deficiencies.