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Related Concept Videos

EPS and iPS Cells in Disease Research01:21

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Embryonic and induced pluripotent stem cells are excellent models for disease research because of their ability to self-renew and differentiate into most cell types. Somatic cells from a patient are isolated and reprogrammed into induced pluripotent stem cells or iPSCs. These iPSCs are later differentiated into the desired cell type, which mirrors the diseased cell of the patient. In this way, disease models have been created for investigating diseases such as Down syndrome, type I diabetes,...
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Modeling the Interplay Between Neurons and Astrocytes in Autism Using Human Induced Pluripotent Stem Cells.

Fabiele Baldino Russo1, Beatriz Camille Freitas2, Graciela Conceição Pignatari3

  • 1Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, São Paulo, Brazil; Department of Surgery, School of Veterinary Medicine, University of São Paulo, São Paulo, São Paulo, Brazil.

Biological Psychiatry
|November 14, 2017
PubMed
Summary
This summary is machine-generated.

Researchers used induced pluripotent stem cells to study autism spectrum disorder (ASD). They found that astrocytes in individuals with ASD impair neuronal development, and blocking interleukin-6 may offer a therapeutic approach for this neurodevelopmental disorder.

Keywords:
ASDAstrocytesAutismCo-culture modelNeuronsiPSCs

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Area of Science:

  • Neuroscience
  • Genetics
  • Stem Cell Biology

Background:

  • Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with largely unknown genetic causes and etiology.
  • Investigating neuronal and glial cell interactions is crucial for understanding ASD pathophysiology.
  • Induced pluripotent stem cells (iPSCs) offer a powerful model for studying cellular mechanisms in ASD.

Purpose of the Study:

  • To investigate neuronal connectivity and astrocyte-neuron interplay in nonsyndromic ASD using iPSC-derived cells.
  • To explore the role of astrocytes in neuronal development and function in ASD models.
  • To identify potential therapeutic targets for ASD based on cellular mechanisms.

Main Methods:

  • Generation of iPSCs from individuals with nonsyndromic ASD and healthy controls.
  • Culturing mixed neural cells and enriched astrocyte populations for co-culture experiments.
  • Analysis of synaptogenesis, neuronal activity (multielectrode array), and gene/protein expression.
  • Measurement of neurotransmitter release and cytokine secretion (interleukin-6).

Main Results:

  • ASD-derived neurons exhibited reduced synaptic gene expression, glutamate release, and spontaneous firing rates.
  • ASD-derived astrocytes impaired neuronal development and synaptogenesis in co-culture models.
  • Blocking interleukin-6 (IL-6) secretion from astrocytes rescued neuronal defects and enhanced synaptogenesis.

Conclusions:

  • Astrocytes play a significant role in the neuronal phenotype observed in a subtype of ASD.
  • Interleukin-6 (IL-6) secreted by astrocytes is implicated in ASD-related neural defects.
  • Targeting glial cell dysfunction, specifically IL-6 signaling, presents a potential therapeutic strategy for ASD.