Department of Cognitive Psychology, Institute for Cognitive and Brain Sciences, Shahid Beheshti University, Tehran 1983969411, Iran.
Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, 8000 Aarhus, Denmark.
Int J Mol Sci. 2021 Jan 25;22(3):1173. doi: 10.3390/ijms22031173.
Environmental Enrichment (EE) has been suggested as a possible therapeutic intervention for neurodevelopmental disorders such as autism. Although the benefits of this therapeutic method have been reported in some animal models and human studies, the unknown pathophysiology of autism as well as number of conflicting results, urge for further examination of the therapeutic potential of EE in autism. Therefore, the aim of this study was to examine the effects of environmental enrichment on autism-related behaviors which were induced in the maternal separation (MS) animal model.
Maternally separated (post-natal day (PND) 1-14, 3h/day) and control male rats were at weaning (PND21) age equally divided into rats housed in enriched environment and normal environment. At adolescence (PND42-50), the four groups were behaviorally tested for direct social interaction, sociability, repetitive behaviors, anxiety behavior, and locomotion. Following completion of the behavioral tests, the blood and brain tissue samples were harvested in order to assess plasma level of brain derived neurotrophic factor (BDNF) and structural plasticity of brain using ELISA and stereological methods respectively.
We found that environmental enrichment reduced repetitive behaviors but failed to improve the impaired sociability and anxiety behaviors which were induced by maternal separation. Indeed, EE exacerbated anxiety and social behaviors deficits in association with increased plasma BDNF level, larger volume of the hippocampus and infra-limbic region and higher number of neurons in the infra-limbic area ( < 0.05). : We conclude that environmental enrichment has a significant improvement effect on the repetitive behavior as one of the core autistic-like behaviors induced by maternal separation but has negative effect on the anxiety and social behaviors which might have been modulated by BDNF.
环境丰容（EE）被提议作为一种可能的治疗干预措施，用于治疗神经发育障碍，如自闭症。尽管这种治疗方法在一些动物模型和人类研究中已经得到了报道，但由于自闭症的未知病理生理学以及许多相互矛盾的结果，需要进一步研究 EE 在自闭症中的治疗潜力。因此，本研究旨在研究环境丰容对在母体分离（MS）动物模型中诱导的自闭症相关行为的影响。
母体分离（产后第 1-14 天，每天 3 小时）和对照组雄性大鼠在断奶（PND21）时等分为在丰富环境和正常环境中饲养的大鼠。在青春期（PND42-50），对四组大鼠进行直接社交互动、社交性、重复性行为、焦虑行为和运动能力的行为测试。完成行为测试后，采集血液和脑组织样本，分别使用 ELISA 和体视学法评估血浆脑源性神经营养因子（BDNF）水平和大脑结构可塑性。
我们发现，环境丰容减少了重复性行为，但未能改善由母体分离引起的社交能力和焦虑行为受损。事实上，EE 加剧了焦虑和社交行为缺陷，同时增加了血浆 BDNF 水平、海马体和下边缘区域的体积以及下边缘区域的神经元数量（<0.05）。结论：环境丰容对由母体分离引起的自闭症样行为之一的重复性行为有显著的改善作用，但对焦虑和社交行为有负面影响，这可能是由 BDNF 调节的。
