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- Ming-Chang Chiang, Christopher J B Nicol, Yu-Ping Yang, Tairui Chiang, and Chiahui Yen.
- Department of Life Science College of Science and Engineering Fu Jen Catholic University New Taipei City 242 Taiwan. Electronic address: 089034@mail.fju.edu.tw.
- Neuroscience. 2025 Feb 3.
BackgroundExposure to PM2.5 is associated with neurotoxicity and mitochondrial dysfunction. Resveratrol, a natural polyphenol, has demonstrated antioxidant and neuroprotective properties. Still, its efficacy in mitigating PM2.5-induced damage in human neural stem cells (hNSCs) and within a 3D scaffold system remains underexplored.ObjectiveThis study investigated the protective effects of resveratrol against PM2.5-induced damage in hNSCs and within a 3D scaffold system.MethodsAssess cell viability using MTT and LIVE/DEAD assays and measure caspase activity by fluorescence analysis. Quantify gene and protein expression of key regulatory pathways using qPCR and Western blotting. Then, mitochondrial function was analyzed by measuring ATP production, mitochondrial mass, maximal respiratory rate, COX activity, membrane potential, TEM, and immunofluorescence staining. In addition, 3D scaffolds created by the CELLINK INKREDIBLE bioprinter were used to study the effect of resveratrol on PM2.5-induced hNSCs damage.ResultsResveratrol significantly improved cell viability and reduced caspase-3 and caspase-9 activities in PM2.5-treated hNSCs. Resveratrol treatment upregulated TrKBR, PI3K, AKT, CREB, PPARα, PPARγ, SIRT1and AMPK expression. It restored mitochondrial function by increasing ATP production, mitochondrial mass, maximal respiratory rate, COX activity, and membrane potential. Using a 3D scaffold demonstrated resveratrol's potential to maintain mitochondrial function and cellular health under PM2.5 exposure.ConclusionResveratrol can effectively reduce neurotoxicity and mitochondrial dysfunction caused by PM2.5 in hNSCs. Its protective effects against PM2.5-induced toxicity in hNSCs within a 3D bioprinted model highlight this study's translational potential. These findings emphasize its potential as a therapeutic agent against environmental neurotoxins and the development of neuroprotective strategies.Copyright © 2025. Published by Elsevier Inc.
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