4.4 Article

Spatial learning and memory function-related gene expression in the hippocampus of mouse exposed to nanoparticle-rich diesel exhaust

Journal

NEUROTOXICOLOGY
Volume 29, Issue 6, Pages 940-947

Publisher

ELSEVIER
DOI: 10.1016/j.neuro.2008.09.007

Keywords

Nanoparticle-rich diesel exhaust; Lipoteichoic acid; Spatial learning; NMDA receptor subunit; Hippocampus

Funding

  1. Japan Society for the Promotion of Science to a foreign researcher [JSPS-06585]
  2. Ministry of Education, Culture, Sports, Science and Technology, Japan

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Diesel exhaust particles are a major constituent of ambient particulate matter, and most particles emitted directly from diesel exhaust are smaller than 1 mu m in diameter. Recently, the toxicity of diesel engine-derived nanoparticles has come to be recognized as an emerging social issue. In the present study, we investigated spatial learning ability and memory function-related gene expressions in mouse hippocampus after the exposure of animals to nanoparticle-rich diesel exhaust (NRDE) with or without a bacterial cell wall component. Lipoteichoic acid (LTA), a cell wall component derived from Staphylococcus aureus, was used to induce systemic inflammation. Male BALB/c mice were exposed to clean air (particle concentration, 4.58 mu g/m(3)) or NRDE (148.86 mu g/m(3)) for 5 h per day on 5 days of the week for 4 weeks in an exposure chamber, with or without the weekly intraperitoneal injection of LTA. On the day after the final day of exposure, we used a Morris water maze apparatus to examine the ability of the animals to perform a spatial learning task. After the completion of the test, the animals were sacrificed and the hippocampus was collected from each mouse; the expressions of NMDA receptor subunits (NR1, NR2A and NR2B), proinflammatory cytokines (IL-1 beta and TNF-alpha) and the oxidative stress marker heme oxygenase 1 were then investigated using real-time RT-PCR. In the Morris water maze task, NRDE/LTA (+) group took a longer time to reach the hidden platform than clear air/LTA (-) group. However, NRDE exposure alone did not affect it. The relative mRNA levels of the NMDA receptor subunits and proinflammatory cytokines were higher in hippocampus of NRDE/LTA (+) group compared to clear air/LTA (-) group. These results indicate that co-exposure of NRDE and LTA could affect spatial learning and memory function-related gene expressions in mouse hippocampus. (c) 2008 Elsevier Inc. All rights reserved.

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