Ponroy Bally Blandine, Murai Keith K
Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, Brain Repair and Integrative Neuroscience Program, Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, QC, Canada.
Front Cell Neurosci. 2021 Aug 18;15:702685. doi: 10.3389/fncel.2021.702685. eCollection 2021.
Down Syndrome (DS) is the most common genetic cause of intellectual disability in which delays and impairments in brain development and function lead to neurological and cognitive phenotypes. Traditionally, a neurocentric approach, focusing on neurons and their connectivity, has been applied to understanding the mechanisms involved in DS brain pathophysiology with an emphasis on how triplication of chromosome 21 leads to alterations in neuronal survival and homeostasis, synaptogenesis, brain circuit development, and neurodegeneration. However, recent studies have drawn attention to the role of non-neuronal cells, especially astrocytes, in DS. Astrocytes comprise a large proportion of cells in the central nervous system (CNS) and are critical for brain development, homeostasis, and function. As triplication of chromosome 21 occurs in all cells in DS (with the exception of mosaic DS), a deeper understanding of the impact of trisomy 21 on astrocytes in DS pathophysiology is warranted and will likely be necessary for determining how specific brain alterations and neurological phenotypes emerge and progress in DS. Here, we review the current understanding of the role of astrocytes in DS, and discuss how specific perturbations in this cell type can impact the brain across the lifespan from early brain development to adult stages. Finally, we highlight how targeting, modifying, and/or correcting specific molecular pathways and properties of astrocytes in DS may provide an effective therapeutic direction given the important role of astrocytes in regulating brain development and function.
唐氏综合征（DS）是导致智力残疾最常见的遗传病因，大脑发育和功能的延迟及损伤会导致神经和认知表型。传统上，一种以神经为中心的方法，聚焦于神经元及其连接，已被应用于理解DS脑病理生理学所涉及的机制，重点是21号染色体三体如何导致神经元存活和稳态、突触形成、脑回路发育及神经退行性变的改变。然而，最近的研究已将注意力引向非神经元细胞，尤其是星形胶质细胞，在DS中的作用。星形胶质细胞在中枢神经系统（CNS）中占细胞的很大比例，对大脑发育、稳态和功能至关重要。由于DS的所有细胞中都发生了21号染色体三体（嵌合型DS除外），因此有必要更深入地了解21号染色体三体对DS病理生理学中星形胶质细胞的影响，这对于确定DS中特定的脑改变和神经表型如何出现和进展可能也是必要的。在此，我们综述了目前对星形胶质细胞在DS中作用的理解，并讨论了这种细胞类型的特定扰动如何在从早期脑发育到成年阶段的整个生命周期中影响大脑。最后，鉴于星形胶质细胞在调节大脑发育和功能中的重要作用，我们强调针对、修饰和/或纠正DS中星形胶质细胞的特定分子途径和特性可能提供一个有效的治疗方向。
