Extracellular glutamate level and NMDA receptor subunit expression in mouse olfactory bulb following nanoparticle-rich diesel exhaust exposure

• Published in: Inhalation toxicology 2009-08, Vol.21 (10), p.828-836
• Main Authors: Win-Shwe, Tin-Tin, Mitsushima, Dai, Yamamoto, Shoji, Fujitani, Yuji, Funabashi, Toshiya, Hirano, Seishiro, Fujimaki, Hidekazu
• Format: Article
• Language: English
• Subjects: Animals; Body Weight - drug effects; Brain - drug effects; Brain - metabolism; Chromatography, High Pressure Liquid; Extracellular Space - metabolism; Glutamic Acid - metabolism; Injections, Intraperitoneal; Male; Mice; Mice, Inbred BALB C; Microdialysis; Nanoparticles - toxicity; Olfactory Bulb - drug effects; Olfactory Bulb - metabolism; Organ Size - drug effects; Particle Size; Receptors, N-Methyl-D-Aspartate - biosynthesis; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - biosynthesis; RNA, Messenger - isolation & purification; Transcription Factors - biosynthesis; Vehicle Emissions - toxicity
• ISSN: 0895-8378; 1091-7691
• DOI: 10.1080/08958370802538068

In this present study, we aimed to investigate the extracellular glutamate level and memory function-related gene expression in the mouse olfactory bulb after exposure of the animals to nanoparticle-rich diesel exhaust (NRDE) with or without 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 μg/m3) or NRDE (148.86 μg/m3) 5 h per day on 5 consecutive days of the week for 4 wk with or without weekly intraperitoneal injection of LTA. We examined the extracellular glutamate levels in the olfactory bulb using in vivo microdialysis and high-performance liquid chromatography assay. Then, we collected the olfactory bulb to examine the expression of N-methyl-D-aspartate (NMDA) receptor subunits (NR1, NR2A, and NR2B) and calcium/calmodulin-dependent protein kinase (CaMK) IV and cyclic AMP response element binding protein (CREB)-1 using real-time reverse-transcription polymerase chain reaction (RT-PCR). NRDE and/or LTA caused significantly increased extracellular glutamate levels in the olfactory bulb of mice. Moreover, the exposure of mice to NRDE upregulates NR1, NR2A, NR2B, and CaMKIV mRNAs in the olfactory bulb, while LTA upregulates only NR2B and CREB1 mRNAs. These findings suggest that NRDE and LTA cause glutamate-induced neurotoxicity separately and accompanied by changes in the expression of NMDA receptor subunits and related kinase and transcription factor in the mouse olfactory bulb. This is the first study to show the correlation between glutamate toxicity and memory function-related gene expressions in the mouse olfactory bulb following exposure to NRDE.