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A Novel In Vitro Live-imaging Assay of Astrocyte-mediated Phagocytosis Using pH Indicator-conjugated Synaptosomes
Published on: February 5, 2018
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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
Summary
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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