Lewis Mark H
McKnight Brain Institute and Department of Psychiatry, University of Florida, Gainesville, Florida 32601, USA.
Ment Retard Dev Disabil Res Rev. 2004;10(2):91-5. doi: 10.1002/mrdd.20017.
Environmental restriction or deprivation early in development can induce social, cognitive, affective, and motor abnormalities similar to those associated with autism. Conversely, rearing animals in larger, more complex environments results in enhanced brain structure and function, including increased brain weight, dendritic branching, neurogenesis, gene expression, and improved learning and memory. Moreover, in animal models of CNS insult (e.g., gene deletion), a more complex environment has attenuated or prevented the sequelae of the insult. Of relevance is the prevention of seizures and attenuation of their neuropathological sequelae as a consequence of exposure to a more complex environment. Relatively little attention, however, has been given to the issue of sensitive periods associated with such effects, the relative importance of social versus inanimate stimulation, or the unique contribution of exercise. Our studies have examined the effects of environmental complexity on the development of the restricted, repetitive behavior commonly observed in individuals with autism. In this model, a more complex environment substantially attenuates the development of the spontaneous and persistent stereotypies observed in deer mice reared in standard laboratory cages. Our findings support a sensitive period for such effects and suggest that early enrichment may have persistent neuroprotective effects after the animal is returned to a standard cage environment. Attenuation or prevention of repetitive behavior by environmental complexity was associated with increased neuronal metabolic activity, increased dendritic spine density, and elevated neurotrophin (BDNF) levels in brain regions that are part of cortical-basal ganglia circuitry. These effects were not observed in limbic areas such as the hippocampus.
发育早期的环境限制或剥夺会诱发与自闭症相关的类似社会、认知、情感和运动异常。相反，在更大、更复杂的环境中饲养动物会导致大脑结构和功能增强，包括脑重量增加、树突分支增多、神经发生、基因表达以及学习和记忆改善。此外，在中枢神经系统损伤的动物模型（如基因缺失）中，更复杂的环境减轻或预防了损伤的后遗症。与此相关的是，由于暴露于更复杂的环境，癫痫发作得到预防，其神经病理后遗症也有所减轻。然而，对于与此类效应相关的敏感期问题、社会刺激与无生命刺激的相对重要性或运动的独特作用，相对较少受到关注。我们的研究考察了环境复杂性对自闭症患者中常见的受限、重复行为发展的影响。在这个模型中，更复杂的环境显著减轻了在标准实验室笼子中饲养的鹿鼠所表现出的自发和持续刻板行为的发展。我们的研究结果支持了此类效应存在敏感期，并表明早期丰富环境在动物回到标准笼子环境后可能具有持续的神经保护作用。环境复杂性对重复行为的减轻或预防与神经元代谢活动增加、树突棘密度增加以及作为皮质 - 基底神经节回路一部分的脑区中神经营养因子（BDNF）水平升高有关。在海马等边缘区域未观察到这些效应。
