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Valproic acid-exposed astrocytes impair inhibitory synapse formation and function

Kotomi Takeda1, Takuya Watanabe2,3, Kohei Oyabu1

  • 1Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, 814-0180, Japan.

Scientific Reports
|January 9, 2021
PubMed

Insights

Valproic acid (VPA) exposure impairs astrocyte function, specifically reducing inhibitory synapses in developing neurons. This astrocyte-mediated neurodevelopmental perturbation may contribute to disorders like autism spectrum disorder.

Area of Science:

  • Neuroscience
  • Developmental Biology
  • Cell Biology

Background:

  • Valproic acid (VPA) is an epilepsy medication with known risks of causing neurodevelopmental disorders in offspring.
  • Astrocytes are crucial for neurodevelopment and synapse function, but their role in VPA's effects is unclear.

Purpose of the Study:

  • To investigate how VPA exposure affects astrocyte function and their influence on neuronal morphology and synapse development.

Main Methods:

  • Primary astrocyte cultures were exposed to VPA.
  • Co-cultures of VPA-exposed astrocytes and neurons were used to assess neuronal morphology and synaptic function.

Main Results:

  • VPA-exposed astrocytes reduced the number of inhibitory synapses and impaired synaptic transmission in inhibitory neurons.
  • Excitatory neuron morphology, synapse number, and synaptic transmission remained unaffected.
  • VPA-exposed astrocytes did not alter the morphology of inhibitory neurons.

Conclusions:

  • VPA exposure specifically impairs astrocyte-mediated synaptogenesis of inhibitory neurons.
  • Maternal VPA use impacts both neurons and astrocytes, leading to disrupted astrocyte-mediated neurodevelopment.

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