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Journal of Nanoparticle Research

, Volume 12, Issue 5, pp 1567–1578 | Cite as

Genomics-based screening of differentially expressed genes in the brains of mice exposed to silver nanoparticles via inhalation

  • Hye-Young Lee
  • You-Jin Choi
  • Eun-Jung Jung
  • Hu-Quan Yin
  • Jung-Taek Kwon
  • Ji-Eun Kim
  • Hwang-Tae Im
  • Myung-Haing Cho
  • Ju-Han Kim
  • Hyun-Young Kim
  • Byung-Hoon LeeEmail author
Research Paper

Abstract

Silver nanoparticles (AgNP) are among the fastest growing product categories in the nanotechnology industry. Despite the importance of AgNP in consumer products and clinical applications, relatively little is known regarding AgNP toxicity and its associated risks. We investigated the effects of AgNP on gene expression in the mouse brain using Affymetrix Mouse Genome Arrays. C57BL/6 mice were exposed to AgNP (geometric mean diameter, 22.18 ± 1.72 nm; 1.91 × 107 particles/cm3) for 6 h/day, 5 days/week using the nose-only exposure system for 2 weeks. Total RNA isolated from the cerebrum and cerebellum was subjected to hybridization. From over 39,000 probe sets, 468 genes in the cerebrum and 952 genes in the cerebellum were identified as AgNP-responsive (one-way analysis of variance; p < 0.05). The largest groups of gene products affected by AgNP exposure included 73 genes in the cerebrum and 144 genes in the cerebellum. AgNP exposure modulated the expression of several genes associated with motor neuron disorders, neurodegenerative disease, and immune cell function, indicating potential neurotoxicity and immunotoxicity associated with AgNP exposure. Real-time PCR data for five genes analyzed from whole blood showed good correlation with the observed changes in the brain. Following rigorous validation and substantiation, these genes may assist in the development of surrogate markers for AgNP exposure and/or toxicity.

Keywords

Brain Inhalation Mice Microarray Silver nanoparticles Toxicity EHS Nanomedicine 

Notes

Acknowledgment

This work was partially supported by the SRC/ERC program of MOST/KOSEF (R11-2007-107-01001-0).

Supplementary material

11051_2009_9666_MOESM1_ESM.jpg (275 kb)
Supplementary Data 1. Pathological analysis of the cerebrum obtained from C57BL/6 mice after inhalation exposure to AgNP. Histopathological analysis of hematoxylin-eosin-stained paraffin sections from (a) control and (b) AgNP cerebrum samples (×100). (JPG 275 kb)
11051_2009_9666_MOESM2_ESM.xls (91 kb)
Supplementary Data 2. Altered Genes compared with control (Bayesian ANOVA; p < 0.05) in the cerebrum. Values represent fold changes on log2 scale compared with control groups. (XLS 91 kb)
11051_2009_9666_MOESM3_ESM.xls (171 kb)
Supplementary Data 3. Altered Genes compared with control (Bayesian ANOVA; p < 0.05) in the cerebellum. Values represent fold changes on log2 scale compared with control groups. (XLS 171 kb)
11051_2009_9666_MOESM4_ESM.xls (28 kb)
Supplementary Data 4. Genes altered more than 1.5-fold (Bayesian ANOVA; p < 0.05) compared with control in the cerebrum. Values represent fold changes on log2 scale compared with control groups. (XLS 28 kb)
11051_2009_9666_MOESM5_ESM.xls (36 kb)
Supplementary Data 5. Genes altered more than 1.5-fold (Bayesian ANOVA; p < 0.05) compared with control in the cerebellum. Values represent fold changes on log2 scale compared with control groups. (XLS 37 kb)

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Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Hye-Young Lee
    • 1
  • You-Jin Choi
    • 1
  • Eun-Jung Jung
    • 1
  • Hu-Quan Yin
    • 1
  • Jung-Taek Kwon
    • 2
  • Ji-Eun Kim
    • 2
    • 4
  • Hwang-Tae Im
    • 2
    • 4
  • Myung-Haing Cho
    • 2
    • 4
  • Ju-Han Kim
    • 3
  • Hyun-Young Kim
    • 5
  • Byung-Hoon Lee
    • 1
    Email author
  1. 1.College of Pharmacy and Research Institute of Pharmaceutical SciencesSeoul National UniversitySeoulRepublic of Korea
  2. 2.College of Veterinary MedicineSeoul National UniversitySeoulRepublic of Korea
  3. 3.College of MedicineSeoul National UniversitySeoulRepublic of Korea
  4. 4.Nano Systems Institute-National Core Research CenterSeoul National UniversitySeoulRepublic of Korea
  5. 5.Chemical Safety and Health Research CenterOccupational Safety and Health Research InstituteDaejeonRepublic of Korea

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