Astrocytes in fragile X syndrome

Astrocytes have an important role in neuronal maturation and synapse function in the brain. The interplay between astrocytes and neurons is found to be altered in many neurodevelopmental disorders, including fragile X syndrome (FXS) that is the most common inherited cause of intellectual disability and autism spectrum disorder. Transcriptional, functional, and metabolic alterations in Fmr1 knockout mouse astrocytes, human FXS stem cell-derived astrocytes as well as in in vivo models suggest autonomous effects of astrocytes in the neurobiology of FXS. Abnormalities associated with FXS astrocytes include differentiation of central nervous system cell populations, maturation and regulation of synapses, and synaptic glutamate balance. Recently, FXS-specific changes were found more widely in astrocyte functioning, such as regulation of inflammatory pathways and maintenance of lipid homeostasis. Changes of FXS astrocytes impact the brain homeostasis and function both during development and in the adult brain and offer opportunities for novel types of approaches for intervention.

• Publication year

  2024

• Venue

  Frontiers in Cellular Neuroscience

• Publication date

  2024-01-08

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.3389/fncel.2023.1322541PMID 38259499PMCID 10800791
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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• A Synaptic Perspective of Fragile X Syndrome and Autism Spectrum Disorders.

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• Prolonged Time Lag to Final Diagnosis of Fragile X Syndrome

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