丰富环境改善抑郁的神经机制研究进展

Neural mechanism of environmental enrichment improving depression

抑郁症是一种以情绪低落为主要表现的常见精神障碍,其病理生理机制复杂且药物治疗效果欠佳。丰富环境(environmental enrichment,EE)是实验室常用的改善大脑功能的干预措施之一,通过将实验室动物暴露于较标准饲养环境更为丰富的感官、运动和/或社会刺激中,而使其获得积极的可塑性和适应性变化。大量研究表明,EE对多种抑郁动物模型都有明显的改善作用,但至今尚未能全面了解其机制,且行为学结果存在差异。由于EE的多维性和复杂性,目前还没有统一的范式标准,因此有必要整合现有的数据,通过理解EE的作用机制,对EE的各结构组成和实施步骤进行完善。文章结合近年来对抑郁动物模型的研究,从促进海马神经发生、减轻神经炎症、调节神经内分泌和影响表观遗传修饰等方面对EE的抗抑郁作用机制进行综述,以期为抑郁症机制研究和治疗提供新思路。随着精准医学和个体化医疗的兴起,人们对探索抑郁个体间差异和群体内效应的来源和机制越来越感兴趣,所以如何根据现有研究发现的作用机制将EE合理翻译至人类社会,是未来将要面临的挑战。

Depression is a common psychiatric disorder characterized by low mood with complex pathophysiological mechanisms and poor effect of pharmacological treatment.The animals were placed in greater sensory,physical and/or social stimuli than those of the standard feeding environment,so that they can obtain positive plasticity and adaptability.Environmental enrichment(EE)is a common intervention to improve brain function in laboratory.A large number of studies have shown that EE had significant ameliorative effects on various animal models of depression,but the mechanisms have not been yet fully understood with outcome heterogeneity in ethology.There was no universally accepted and unified paradigm and standard for EE due to its multi-dimensionality and complexity.Therefore,it is necessary to improve the structural components and implementation steps of EE by integrating the existing data.Combined with recent studies on animal models of depression,this paper reviewed the anti-depression mechanism of EE from promoting hippocampal neurogenesis,reducing neuroinflammation,regulating neuroendocrine and affecting epigenetic modifications,in order to provide new ideas for mechanisms research and treatment of depression.As the rise of precision medicine and individualized medicine brings human growing interest in exploring the sources and mechanisms of inter-individual differences and intra-group effects of depression,it will be a challenge to translate EE to the human society in a rational way.