title: Neurotoxic potential of iron oxide nanoparticles in the rat brain striatum and hippocampus.
abstract: It has recently been reported that iron oxide nanoparticles (Fe(3)O(4)-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 Fe(3)O(4)-NPs and their potential to confer striatum and hippocampus neurotoxicity. This study focuses on the effects of Fe(3)O(4)-NPs on the striatum and hippocampus, including oxidative injury and the accumulation and retention of Fe(3)O(4)-NPs. This study also explores the molecular mechanism of oxidative damage in dopaminergic neurons; we were able to assess the neurotoxic effects of Fe(3)O(4)-NPs by incubating dopaminergic neurons with radioactive Fe(3)O(4)-NPs. A regional distribution of Fe(3)O(4)-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 Fe(3)O(4)-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 Fe(3)O(4)-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 Fe(3)O(4)-NPs may play a role in the development of neurodegenerative diseases.
authors.affiliation: Shanghai Biomaterials Research and Testing Center, Shanghai Key Laboratory of Stomatology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200023, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
authors.forename: Tingting
authors.initials: T
authors.lastname: Ding
authors.forename: Jiao
authors.initials: J
authors.lastname: Sun
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001479:Basal Ganglia / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004789:Enzyme Activation; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D058185:Magnetite Nanoparticles / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014018:Tissue Distribution; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D058185:Magnetite Nanoparticles; D016159:Tumor Suppressor Protein p53; D048031:JNK Mitogen-Activated Protein Kinases