Neurotoxicity Research

, Volume 32, Issue 2, pp 187–203 | Cite as

Neurobehavioural Toxicity of Iron Oxide Nanoparticles in Mice

  • Vasanth Dhakshinamoorthy
  • Vijayprakash Manickam
  • Ekambaram Perumal


Iron oxide nanoparticles (Fe2O3-NPs) are widely used in various biomedical applications, extremely in neurotheranostics. Simultaneously, Fe2O3-NP usage is of alarming concern, as its exposure to living systems causes deleterious effects due to its redox potential. However, study on the neurobehavioural impacts of Fe2O3-NPs is very limited. In this regard, adult male mice were intraperitoneally administered with Fe2O3-NPs (25 and 50 mg/kg body weight) once a week for 4 weeks. A significant change in locomotor behaviour and spatial memory was observed in Fe2O3-NP-treated animals. Damages to blood–brain barrier permeability by Fe2O3-NPs and their accumulation in brain regions were evidenced by Evan’s blue staining, iron estimation and Prussian blue staining. Elevated nitric oxide, acetylcholinesterase, lactate dehydrogenase leakage and demyelination were observed in the Fe2O3-NP-exposed brain tissues. Imbalanced levels of ROS generation and antioxidant defence mechanism (superoxide dismutase and catalase) cause damages to lipids, proteins and DNA. PARP and cleaved caspase 3 expression levels were found to be increased in the Fe2O3-NP-exposed brain regions which confirms DNA damage and apoptosis. Thus, repeated Fe2O3-NP exposure causes neurobehavioural impairments by nanoparticle accumulation, oxidative stress and apoptosis in the mouse brain.


Apoptosis Fe2O3-NPs Locomotor behaviour Oxidative stress Spatial memory 



This work was supported by the University Grants Commission—Special Assistance Programme (UGC-SAP-II:F-3-20/2013) and Department of Science and Technology, Fund for Improvement of S&T infrastructure in universities and higher educational institutions (DST-FIST:SR/FST/LSI-618/2014), New Delhi, India. Vijayprakash Manickam acknowledges the UGC-BSR fellowship (UGC-BSR-No.F.7-25/2007) funded by UGC-BSR, New Delhi, India.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

Supplementary material

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ESM 1 (DOCX 522 kb)
12640_2017_9721_MOESM2_ESM.docx (331 kb)
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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Vasanth Dhakshinamoorthy
    • 1
  • Vijayprakash Manickam
    • 1
  • Ekambaram Perumal
    • 1
  1. 1.Molecular Toxicology Laboratory, Department of BiotechnologyBharathiar UniversityCoimbatoreIndia

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