Neurotoxic potential of iron oxide nanoparticles in the rat brain striatum and hippocampus

It has recently been reported that iron oxide nanoparticles (Fe3O4-NPs, 30 nm) have the ability to translocate directly from the olfactory nerve to the brain. The striatum and hippocampus are important structures in the brain and are associated with the development of Parkinson's and Alzheimer's diseases. Therefore, it is critical to evaluate Fe3O4-NPs and their potential to confer striatum and hippocampus neurotoxicity. This study focuses on the effects of Fe3O4-NPs on the striatum and hippocampus, including oxidative injury and the accumulation and retention of Fe3O4-NPs. This study also explores the molecular mechanism of oxidative damage in dopaminergic neurons; we were able to assess the neurotoxic effects of Fe3O4-NPs by incubating dopaminergic neurons with radioactive Fe3O4-NPs. A regional distribution of Fe3O4-NPs was observed in rat brains after the particles were intranasally instilled for seven days. The particles were found to be deposited at particularly high concentrations in the rat striata and hippocampi. Over half of the Fe3O4-NPs were retained in the striata for a minimum of 14 days, and may have induced oxidative damage to the region. However, no injuries were observed in the hippocampi. These in vitro studies demonstrate that Fe3O4-NPs may decrease neuron viability, trigger oxidative stress, and activate JNK- and p53-mediated pathways to regulate the cell cycle and apoptosis. These results also suggest that environmental exposure to Fe3O4-NPs may play a role in the development of neurodegenerative diseases. (C) 2012 Elsevier Inc. All rights reserved.