Bessetti · 2025 · Molecular psychiatry
Oxidative stress and synapses in cultured neurons
Did NRF2 activation change the response to VPA exposure in cultured neurons?
In vitro · human-derived and mouse neurons
Key findings
Activation of cellular defense pathways
SFN increased NRF2 and antioxidant gene expression in the model.
Attenuation of synaptic changes
A reduction in the loss of synapse formation caused by VPA exposure was reported.
Neural activity response was also assessed.
Recovery of neural activity reduced by VPA was observed in mouse cortical neurons.
Detailed results
Whether developing neural networks could be protected from oxidative stress was examined.
Human induced pluripotent stem cell (iPSC)-derived neurodevelopmental models and mouse cortical neurons were cultured. VPA exposure created experimental conditions with reduced synapse formation and neural activity, and changes after sulforaphane treatment were compared.
Synapses are connections through which neurons exchange signals. This study measured cellular defense genes, synapse-related genes and structures, and neural activity to explore links between molecular changes and network function.
Clues linking gene responses to synapse formation and neural activity
In the human-derived model, sulforaphane increased NRF2 and antioxidant gene expression and reduced oxidative stress. Expression of genes related to synapse formation also rose, and VPA-induced reduction in synapse formation was attenuated.
Mouse cortical neurons showed recovery of neural activity reduced by VPA. Antioxidant responses and neuronal connectivity and function were also examined.
Protective response in a VPA exposure model
A protective response was observed after sulforaphane treatment in cultured cells with VPA-induced changes in synapses and neuronal activity.
Study design
A culture model in which VPA exposure causes oxidative stress and synaptic changes was used. NRF2 activity, gene expression, synapse formation, and neuronal activity were compared after SFN treatment.
- Participants
- Human iPSC-derived neurodevelopmental model
Mouse cortical neurons - Intake and observation
- VPA and SFN treatment in cultured cells
NRF2, gene expression, and neural activity analyses - Measures
- Antioxidant genes, oxidative stress, synapse number, and neural activity
Study context
Human-derived neurodevelopmental models and mouse neurons were cultured to observe changes after VPA and SFN treatment.
Original paper and sources
Sulforaphane protects developing neural networks from VPA-induced synaptic alterations.
- Journal
- Molecular psychiatry · 2025 · 30(9): 3868-3884
- First published
- 2025-04-02