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Iron Oxide Nanoparticles Induce Dopaminergic Damage: In vitro Pathways and In Vivo Imaging Reveals Mechanism of Neuronal Damage

Overview of attention for article published in Molecular Neurobiology, June 2015
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Title
Iron Oxide Nanoparticles Induce Dopaminergic Damage: In vitro Pathways and In Vivo Imaging Reveals Mechanism of Neuronal Damage
Published in
Molecular Neurobiology, June 2015
DOI 10.1007/s12035-015-9259-2
Pubmed ID
Authors

Syed Z. Imam, Susan M. Lantz-McPeak, Elvis Cuevas, Hector Rosas-Hernandez, Serguei Liachenko, Yongbin Zhang, Sumit Sarkar, Jaivijay Ramu, Bonnie L. Robinson, Yvonne Jones, Bobby Gough, Merle G. Paule, Syed F. Ali, Zbigniew K. Binienda

Abstract

Various iron-oxide nanoparticles have been in use for a long time as therapeutic and imaging agents and for supplemental delivery in cases of iron-deficiency. While all of these products have a specified size range of ∼40 nm and above, efforts are underway to produce smaller particles, down to ∼1 nm. Here, we show that after a 24-h exposure of SHSY-5Y human neuroblastoma cells to 10 μg/ml of 10 and 30 nm ferric oxide nanoparticles (Fe-NPs), cellular dopamine content was depleted by 68 and 52 %, respectively. Increases in activated tyrosine kinase c-Abl, a molecular switch induced by oxidative stress, and neuronal α-synuclein expression, a protein marker associated with neuronal injury, were also observed (55 and 38 % percent increases, respectively). Inhibition of cell-proliferation, significant reductions in the number of active mitochondria, and a dose-dependent increase in reactive oxygen species (ROS) were observed in neuronal cells. Additionally, using a rat in vitro blood-brain barrier (BBB) model, a dose-dependent increase in ROS accompanied by increased fluorescein efflux demonstrated compromised BBB integrity. To assess translational implications, in vivo Fe-NP-induced neurotoxicity was determined using in vivo MRI and post-mortem neurochemical and neuropathological correlates in adult male rats after exposure to 50 mg/kg of 10 nm Fe-NPs. Significant decrease in T 2 values was observed. Dynamic observations suggested transfer and retention of Fe-NPs from brain vasculature into brain ventricles. A significant decrease in striatal dopamine and its metabolites was also observed, and neuropathological correlates provided additional evidence of significant nerve cell body and dopaminergic terminal damage as well as damage to neuronal vasculature after exposure to 10 nm Fe-NPs. These data demonstrate a neurotoxic potential of very small size iron nanoparticles and suggest that use of these ferric oxide nanoparticles may result in neurotoxicity, thereby limiting their clinical application.

Twitter Demographics

The data shown below were collected from the profiles of 2 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 39 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Norway 1 3%
Unknown 38 97%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 9 23%
Student > Master 8 21%
Researcher 6 15%
Unspecified 5 13%
Other 3 8%
Other 8 21%
Readers by discipline Count As %
Agricultural and Biological Sciences 10 26%
Unspecified 7 18%
Biochemistry, Genetics and Molecular Biology 5 13%
Chemistry 4 10%
Pharmacology, Toxicology and Pharmaceutical Science 3 8%
Other 10 26%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 09 October 2015.
All research outputs
#10,714,444
of 13,465,271 outputs
Outputs from Molecular Neurobiology
#1,458
of 2,221 outputs
Outputs of similar age
#157,968
of 232,092 outputs
Outputs of similar age from Molecular Neurobiology
#19
of 39 outputs
Altmetric has tracked 13,465,271 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,221 research outputs from this source. They receive a mean Attention Score of 4.6. This one is in the 22nd percentile – i.e., 22% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 232,092 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 17th percentile – i.e., 17% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 39 others from the same source and published within six weeks on either side of this one. This one is in the 38th percentile – i.e., 38% of its contemporaries scored the same or lower than it.