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

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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.

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Acknowledgment

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

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Authors and Affiliations

  1. College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, San 56-1, Sillim-dong, Gwanak-gu, Seoul, 151-742, Republic of Korea

    Hye-Young Lee, You-Jin Choi, Eun-Jung Jung, Hu-Quan Yin & Byung-Hoon Lee

  2. College of Veterinary Medicine, Seoul National University, San 56-1, Sillim-dong, Gwanak-gu, Seoul, 151-742, Republic of Korea

    Jung-Taek Kwon, Ji-Eun Kim, Hwang-Tae Im & Myung-Haing Cho

  3. College of Medicine, Seoul National University, San 56-1, Sillim-dong, Gwanak-gu, Seoul, 151-742, Republic of Korea

    Ju-Han Kim

  4. Nano Systems Institute-National Core Research Center, Seoul National University, Seoul, 151-742, Republic of Korea

    Ji-Eun Kim, Hwang-Tae Im & Myung-Haing Cho

  5. Chemical Safety and Health Research Center, Occupational Safety and Health Research Institute, Daejeon, 305-380, Republic of Korea

    Hyun-Young Kim

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  1. Hye-Young Lee
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Correspondence to Byung-Hoon Lee.

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Hye-Young Lee and You-Jin Choi contributed equally to this work.

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11051_2009_9666_MOESM1_ESM.jpg

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

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

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

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

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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Lee, HY., Choi, YJ., Jung, EJ. et al. Genomics-based screening of differentially expressed genes in the brains of mice exposed to silver nanoparticles via inhalation. J Nanopart Res 12, 1567–1578 (2010). https://doi.org/10.1007/s11051-009-9666-2

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