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Abstract Prenatal brain development is particularly sensitive to chemicals that can disrupt synapse formation and cause neurodevelopmental disorders. In most cases, such chemicals increase cellular oxidative stress. For example, prenatal exposure to the anti-epileptic drug valproic acid (VPA), induces oxidative stress and synaptic alterations, promoting autism spectrum disorders (ASD) in humans and autism-like behaviors in rodents. Using VPA to model chemically induced ASD, we tested whether activation of cellular mechanisms that increase antioxidant gene expression would be sufficient to prevent VPA-induced synaptic alterations. As a master regulator of cellular defense pathways, the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) promotes expression of detoxification enzymes and antioxidant gene products. To increase NRF2 activity, we used the phytochemical and potent NRF2 activator, sulforaphane (SFN). In our models of human neurodevelopment, SFN activated NRF2, increasing expression of antioxidant genes and preventing oxidative stress. SFN also enhanced expression of genes associated with synapse formation. Consistent with these gene expression profiles, SFN protected developing neural networks from VPA-induced reductions in synapse formation. Furthermore, in mouse cortical neurons, SFN rescued VPA-induced reductions in neural activity. These results demonstrate the ability of SFN to protect developing neural networks during the vulnerable period of synapse formation, while also identifying molecular signatures of SFN-mediated neuroprotection that could be relevant for combatting other environmental toxicants.
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This content will become publicly available on January 27, 2026
Poly(curcumin-co-poly(ethylene glycol)) films provide neuroprotection following reactive oxygen species insult in vitro
Abstract Objective.Curcumin is an antioxidant and anti-inflammatory molecule that may provide neuroprotection following central nervous system injury. However, curcumin is hydrophobic, limiting its ability to be loaded and then released from biomaterials for neural applications. We previously developed polymers containing curcumin, and these polymers may be applied to neuronal devices or to neural injury to promote neuroprotection. Thus, our objective was to evaluate two curcumin polymers as potential neuroprotective materials for neural applications.Approach.For each curcumin polymer, we created three polymer solutions by varying the weight percentage of curcumin polymer in solvent. These solutions were subsequently coated onto glass coverslips, and the thickness of the polymer was assessed using profilometry. Polymer degradation and dissolution was assessed using brightfield microscopy, scanning electron microscopy, and gel permeation chromatography. The ability of the polymers to protect cortical neurons from free radical insult was assessed using anin vitrocortical culture model.Main results.The P50 curcumin polymer (containing greater poly(ethylene glycol) content than the P75 polymer), eroded readily in solution, with erosion dependent on the weight percentage of polymer in solvent. Unlike the P50 polymer, the P75 polymer did not undergo erosion. Since the P50 polymer underwent erosion, we expected that the P50 polymer would more readily protect cortical neurons from free radical insult. Unexpectedly, even though P75 films did not erode, P75 polymers protected neurons from free radical insult, suggesting that erosion is not necessary for these polymers to enable neuroprotection.Significance.This study is significant as it provides a framework to evaluate polymers for future neural applications. Additionally, we observed that some curcumin polymers do not require dissolution to enable neuroprotection. Future work will assess the ability of these materials to enable neuroprotection withinin vivomodels of neural injury.
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- Award ID(s):
- 2217513
- PAR ID:
- 10599568
- Publisher / Repository:
- IOP
- Date Published:
- Journal Name:
- Journal of Neural Engineering
- Volume:
- 22
- Issue:
- 1
- ISSN:
- 1741-2560
- Page Range / eLocation ID:
- 016015
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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