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长期环境富集促进发育性髓鞘形成。

Prolonged Environmental Enrichment Promotes Developmental Myelination.

作者信息

Goldstein Evan Z, Pertsovskaya Vera, Forbes Thomas A, Dupree Jeffrey L, Gallo Vittorio

机构信息

Center for Neuroscience Research, Children's Research Institute, Children's National Hospital, Washington, DC, United States.

School of Medicine and Health Sciences, The George Washington University, Washington, DC, United States.

出版信息

Front Cell Dev Biol. 2021 Apr 26;9:665409. doi: 10.3389/fcell.2021.665409. eCollection 2021.

Abstract

Postnatal neurodevelopment is profoundly influenced by environmental experiences. Environmental enrichment is a commonly used experimental paradigm that has uncovered numerous examples of experience-dependent plasticity in health and disease. However, the role of environmental enrichment in normal development, especially glial development, is largely unexplored. Oligodendrocytes, the myelin-forming glia in the central nervous system, provide metabolic support to axons and establish efficient saltatory conduction by producing myelin. Indeed, alterations in myelin are strongly correlated with sensory, cognitive, and motor function. The timing of developmental myelination is uniquely positioned to be influenced by environmental stimuli, as peak myelination occurs postnatally and continues into adulthood. To determine if developmental myelination is impacted by environmental experience, mice were housed in an enriched environment during peak myelination through early adulthood. Using translating ribosome affinity purification, oligodendrocyte-specific RNAs were isolated from subcortical white matter at various postnatal ages. RNA-sequencing revealed that differences in the oligodendrocyte translatome were predominantly evident after prolonged and continuous environmental enrichment. These translational changes corresponded with altered oligodendrocyte lineage cell dynamics and enhanced myelination. Furthermore, consistent with increased developmental myelination, enriched mice displayed enhanced motor coordination on a beam walking task. These findings indicate that protracted environmental stimulation is sufficient to modulate developmental myelination and to promote behavioral function.

摘要

出生后的神经发育受到环境经历的深刻影响。环境富集是一种常用的实验范式,它揭示了健康和疾病中许多依赖于经验的可塑性实例。然而,环境富集在正常发育,尤其是胶质细胞发育中的作用在很大程度上尚未得到探索。少突胶质细胞是中枢神经系统中形成髓鞘的胶质细胞,为轴突提供代谢支持,并通过产生髓鞘建立高效的跳跃传导。事实上,髓鞘的改变与感觉、认知和运动功能密切相关。发育性髓鞘形成的时间恰好处于受环境刺激影响的位置,因为髓鞘形成的高峰期发生在出生后并持续到成年期。为了确定发育性髓鞘形成是否受到环境经历的影响,在髓鞘形成高峰期到成年早期,将小鼠饲养在富集环境中。使用翻译核糖体亲和纯化技术,在不同的出生后年龄从皮质下白质中分离出少突胶质细胞特异性RNA。RNA测序显示,在长期持续的环境富集后,少突胶质细胞翻译组的差异主要明显。这些翻译变化与少突胶质细胞谱系细胞动力学的改变和髓鞘形成的增强相对应。此外,与发育性髓鞘形成增加一致,富集环境饲养的小鼠在走平衡木任务中表现出增强的运动协调性。这些发现表明,长期的环境刺激足以调节发育性髓鞘形成并促进行为功能。

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