Santos, TiagoFerreira, RaquelQuartin, EmanuelBoto, CarlosSaraiva, ClaudiaBragança, JoséPeca, JoaoRodrigues, CeciliaFerreira, LinoBernardino, Liliana2019-11-202019-11-202017-091742-70611878-7568http://hdl.handle.net/10400.1/13019Neurogenic niches constitute a powerful endogenous source of new neurons that can be used for brain repair strategies. Neuronal differentiation of these cells can be regulated by molecules such as retinoic acid (RA) or by mild levels of reactive oxygen species (ROS) that are also known to upregulate RA receptor alpha (RAR alpha) levels. Data showed that neural stem cells from the subventricular zone (SVZ) exposed to blue light (405 nm laser) transiently induced NADPH oxidase-dependent ROS, resulting in beta-catenin activation and neuronal differentiation, and increased RAR alpha levels. Additionally, the same blue light stimulation was capable of triggering the release of RA from light-responsive nanoparticles (LR-NP). The synergy between blue light and LR-NP led to amplified neurogenesis both in vitro and in vivo, while offering a temporal and spatial control of RA release. In conclusion, this combinatory treatment offers great advantages to potentiate neuronal differentiation, and provides an innovative and efficient application for brain regenerative therapies. Statement of Significance Controlling the differentiation of stem cells would support the development of promising brain regenerative therapies. Blue light transiently increased reactive oxygen species, resulting in neuronal differentiation and increased retinoic acid receptor (RAR alpha) levels. Additionally, the same blue light stimulation was capable of triggering the release of RA from light-responsive nanoparticles (LR-NP). The synergy between blue light and LR-NP led to amplified neurogenesis, while offering a temporal and spatial control of RA release. In this sense, our approach relying on the modulation of endogenous stem cells for the generation of new neurons may support the development of novel clinical therapies. (C) 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.engNeural stem-cellsCentral-nervous-systemSubventricular zoneAdult neurogenesisWnt/Beta-cateninNadph oxidasesGtpase rac1BrainDifferentiationActivationjournal article10.1016/j.actbio.2017.06.044