Journal
JOURNAL OF MOLECULAR NEUROSCIENCE
Volume 48, Issue 2, Pages 464-471Publisher
HUMANA PRESS INC
DOI: 10.1007/s12031-012-9756-y
Keywords
Zinc oxide nanoparticles; Zn2+; PC12 cells; Olfactory bulb-brain pathway
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ZnO nanoparticles (ZnO-NPs) are widely used in the engineering and cosmetic industries, and inhaled airborne particles pose a known hazard to human health; their translocation into humans is a recognized public health concern. The pulmonary-blood pathway for ZnO-NP toxicity is well documented, but whether translocation of these particles can also occur via an olfactory bulb-brain route remains unclear. The potential toxicity of ZnO-NPs for the human central nervous system (CNS) is predicated on the possibility of their translocation. Our study investigated translocation of ZnO-NPs both in vitro using the neuronal cell line PC12 and in vivo in a Sprague-Dawley rat model. Our findings indicate that the zinc-binding dye, Newport-Green DCF, binds ZnO stoichiometrically and that ZnO-NP concentration can therefore be measured by the fluorescence intensity of the bound dye in confocal fluorescence microscopy. Confocal data obtained using Newport-Green DCF-2 K+-conjugated ZnO-NPs along with the membrane probe FM1-43 demonstrated endocytosis of ZnO-NPs by PC12 cells. In addition, Fluozin-3 measurement showed elevation of cytosolic Zn2+ concentration in these cells. Following in vivo nasal exposure of rats to airborne ZnO-NPs, olfactory bulbs and brains that were examined by Newport-Green fluorescence and TEM particle measurement clearly showed the presence of ZnO-NPs in brain. We conclude that an olfactory bulb-brain translocation pathway for airborne ZnO-NPs exists in rats, and that endocytosis is required for interneuron translocation of these particles.
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