Abstract
Neurodevelopmental disorders arise from genetic and/or from environmental factors and are characterized by different degrees of intellectual disability. The mechanisms that govern important processes sustaining learning and memory, which are severely affected in intellectual disability, have classically been thought to be exclusively under neuronal control. However, this vision has recently evolved into a more integrative conception in which astroglia, rather than just acting as metabolic supply and structural anchoring for neurons, interact at distinct levels modulating neuronal communication and possibly also cognitive processes. Recently, genetic tools have made it possible to specifically manipulate astrocyte activity unraveling novel functions that involve astrocytes in memory function in the healthy brain. However, astrocyte manipulation has also underscored potential mechanisms by which dysfunctional astrocytes could contribute to memory deficits in several neurodevelopmental disorders revealing new pathogenic mechanisms in intellectual disability. Here, we review the current knowledge about astrocyte dysfunction that might contribute to learning and memory impairment in neurodevelopmental disorders, with special focus on Fragile X syndrome and Down syndrome.
Highlights
Neurodevelopmental disorders are multifaceted conditions characterized by different degrees of intellectual disability and impairment in communication and motor skills, among others
Neurodevelopmental disorders such as Down syndrome (DS), Fragile X syndrome (FXS), or Rett syndrome have been considered as synaptopathies [3,4,5], characterized by neuronal alterations important for learning and memory, including abnormalities in dendritic architecture [6,7], with changes in the complexity of dendritic arborizations [7], and in spine number [6,7,8,9,10,11,12], shape and length [7,10,13], reflecting more immature spines [10,14]
Increasing body of evidence suggests that changes in astrocyte physiology and morphology might be involved in Alzheimer’s disease, FXS, or DS, among others [35,36,37,38,39]. Astrocytes modify their function and exhibit some common pathological features including an increase in the number and size of astrocytes together with increased expression of astroglial proteins such as S100 calcium-binding protein β (S100β) [40,41,42,43], a calcium binding protein coded by a HSA21 gene, and the glial fibrillary acidic protein GFAP [36,43,44,45], the main intermediate filament proteins of mature astrocytes
Summary
Neurodevelopmental disorders are multifaceted conditions characterized by different degrees of intellectual disability and impairment in communication (verbal and non-verbal) and motor skills, among others. Increasing body of evidence suggests that changes in astrocyte physiology and morphology might be involved in Alzheimer’s disease, FXS, or DS, among others [35,36,37,38,39] In these pathological conditions, astrocytes modify their function and exhibit some common pathological features including an increase in the number and size of astrocytes together with increased expression of astroglial proteins such as S100 calcium-binding protein β (S100β) [40,41,42,43], a calcium binding protein coded by a HSA21 gene, and the glial fibrillary acidic protein GFAP [36,43,44,45], the main intermediate filament proteins of mature astrocytes. We describe the main astroglial alterations in FXS and DS and propose new lines of research that may help to better understand the role of astrocytes in memory dysfunction
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