Novel object recognition ability in female mice following exposure to nanoparticle-rich diesel exhaust.
Recently, our laboratory reported that exposure to nanoparticle-rich diesel exhaust (NRDE) for 3 months impaired hippocampus-dependent spatial learning ability and up-regulated the expressions of memory function-related genes in the hippocampus of female mice. However, whether NRDE affects the hippocampus-dependent non-spatial learning ability and the mechanism of NRDE-induced neurotoxicity was unknown. Female BALB/c mice were exposed to clean air, middle-dose NRDE (M-NRDE, 47 μg/m(3)), high-dose NRDE (H-NRDE, 129 μg/m(3)), or filtered H-NRDE (F-DE) for 3 months. We then investigated the effect of NRDE exposure on non-spatial learning ability and the expression of genes related to glutamate neurotransmission using a novel object recognition test and a real-time RT-PCR analysis, respectively. We also examined microglia marker Iba1 immunoreactivity in the hippocampus using immunohistochemical analyses. Mice exposed to H-NRDE or F-DE could not discriminate between familiar and novel objects. The control and M-NRDE-exposed groups showed a significantly increased discrimination index, compared to the H-NRDE-exposed group. Although no significant changes in the expression levels of the NMDA receptor subunits were observed, the expression of glutamate transporter EAAT4 was decreased and that of glutamic acid decarboxylase GAD65 was increased in the hippocampus of H-NRDE-exposed mice, compared with the expression levels in control mice. We also found that microglia activation was prominent in the hippocampal area of the H-NRDE-exposed mice, compared with the other groups. These results indicated that exposure to NRDE for 3 months impaired the novel object recognition ability. The present study suggests that genes related to glutamate metabolism may be involved in the NRDE-induced neurotoxicity observed in the present mouse model.
Center for Environmental Health Sciences, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki 305-8506, Japan. tin.tin.win.shwe@nies.go.jp
Tin-Tin
TT
Win-Shwe
Hidekazu
H
Fujimaki
Yuji
Y
Fujitani
Seishiro
S
Hirano
D000818:Animals; D004305:Dose-Response Relationship, Drug; D050581:Excitatory Amino Acid Transporter 4 / Q000032:analysis; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005968:Glutamate Decarboxylase / Q000032:analysis; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects; D019570:Inhalation Exposure / Q000009:adverse effects; D007858:Learning / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000633:toxicity*; D060888:Real-Time Polymerase Chain Reaction; D021641:Recognition, Psychology / Q000187:drug effects*; D001335:Vehicle Emissions / Q000633:toxicity*
D050581:Excitatory Amino Acid Transporter 4; C493390:Slc1a6 protein, mouse; D001335:Vehicle Emissions; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2