In utero exposure of mice to diesel exhaust particles affects spatial learning and memory with reduced N-methyl-D-aspartate receptor expression in the hippocampus of male offspring.
Diesel exhaust consists of diesel exhaust particles (DEPs) and gaseous compounds. Previous studies reported that in utero exposure to diesel exhaust affects the central nervous system. However, there was no clear evidence that these effects were caused by diesel exhaust particles themselves, gaseous compounds, or both. Here, we explored the effects of in utero exposure to DEPs on learning and memory in male ICR mice. DEP solutions were administered subcutaneously to pregnant ICR mice at a dose of 0 or 200 μg/kg body weight on gestation days 6, 9, 12, 15, and 18. We examined learning and memory in 9-to-10-week-old male offspring using the Morris water maze test and passive avoidance test. Immediately after the behavioral tests, hippocampi were isolated. Hippocampal N-methyl-D-aspartate receptor (NR) expression was also measured by quantitative RT-PCR analysis. Mice exposed to DEPs in utero showed deficits in the Morris water maze test, but their performance was not significantly different from that of control mice in the passive avoidance test. In addition, DEP-exposed mice exhibited decreased hippocampal NR2A expression. The present results indicate that maternal DEP exposure disrupts learning and memory in male offspring, which is associated with reduced hippocampal NR2A expression.
The Center for Environmental Health Science for the Next Generation, Research Institute for Science and Technology, Organization for Research Advancement, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan; Department of Hygiene Chemistry, School of Pharmaceutical Sciences, Ohu University, 31-3 Misumido, Tomita, Koriyama, Fukushima 963-8611, Japan. Electronic address: satoshi_yokota1008@yahoo.co.jp.
Satoshi
S
Yokota
The Center for Environmental Health Science for the Next Generation, Research Institute for Science and Technology, Organization for Research Advancement, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan. Electronic address: thanksgivingday0907@hotmail.com.
Akira
A
Sato
The Center for Environmental Health Science for the Next Generation, Research Institute for Science and Technology, Organization for Research Advancement, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan. Electronic address: masa-ume@rs.noda.tus.ac.jp.
Masakazu
M
Umezawa
Department of Hygiene Chemistry, School of Pharmaceutical Sciences, Ohu University, 31-3 Misumido, Tomita, Koriyama, Fukushima 963-8611, Japan. Electronic address: s-oshio@pha.ohu-u.ac.jp.
Shigeru
S
Oshio
The Center for Environmental Health Science for the Next Generation, Research Institute for Science and Technology, Organization for Research Advancement, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan. Electronic address: takedak@rs.noda.tus.ac.jp.
Ken
K
Takeda
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D005865:Gestational Age; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000097:blood / Q000139:chemically induced*; D051379:Mice; D008813:Mice, Inbred ICR; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D012333:RNA, Messenger / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D065853:Spatial Learning / Q000187:drug effects*; D001335:Vehicle Emissions / Q000633:toxicity*
D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D001335:Vehicle Emissions; D003345:Corticosterone
Diesel exhaust particles; Hippocampus; Learning; Maternal exposure; Memory; N-methyl-d-aspartate receptor