Are synapses targets of nanoparticles?

Abstract

The last few years have been marked by real breakthroughs in the field of nanotechnology. Application of nanoparticles was proposed for diagnosis and treatment of different central nervous system diseases. Exposure to nanoparticles in vivo increases the risk of onset of neurodegenerative diseases and nanoparticles are apparently able to kill neurons in vitro. We suggested that presynaptic terminals of neurons are another target for nanoparticles, beyond the already established microglial cells. Ferritin was chosen as a prototypic nanoparticle model. We found that even a high concentration of ferritin, 800 μg/ml, was not able to induce spontaneous release of [14C]glutamate. In contrast, [14C]glutamate uptake was inhibited by ferritin in a dose-dependent fashion. As a next step, the influence of ferritin on the formation of reactive oxygen species was monitored using the fluorescent dye DCFH-DA (2′,7′-dichlorofluorescein diacetate). It was shown that ferritin leads to a dose-dependent formation of free radicals. We found that the ferritin-mediated changes in glutamatergic neurotransmission at presynaptic endings can result in neuronal damage and finally neurodegeneration.