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Review
. 2021 Aug 18:15:702685.
doi: 10.3389/fncel.2021.702685. eCollection 2021.

Astrocytes in Down Syndrome Across the Lifespan

Blandine Ponroy Bally  1 , Keith K Murai  1
Affiliations
Review

Astrocytes in Down Syndrome Across the Lifespan

Blandine Ponroy Bally et al. Front Cell Neurosci. .

Abstract

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.

Keywords: Alzheimer’s disease; Down Syndrome; astrocyte; glia; intellectual disability; neurodevelopment.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
APP overexpression in neuroprogenitor cells decreases Shh signaling and is believed to be responsible for an increase in astrogliogenesis and a decrease in neurogenesis. Created with Biorender.com.
FIGURE 2
FIGURE 2
Reductions in the astrocytic production and secretion of TSP-1 from DS cells causes abnormal dendritic spine shape and number in vitro. Created with Biorender.com.
FIGURE 3
FIGURE 3
Implication of astrocytes in the GABA switch in DS. Created with Biorender.com.
FIGURE 4
FIGURE 4
Astrocytic oxidative stress and mitochondrial dysfunction in neuronal death. Created with Biorender.com.
FIGURE 5
FIGURE 5
Astrocytes as drivers of Aß pathology in the DS brain? Created with Biorender.com.
See this image and copyright information in PMC

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