In utero exposure to diesel exhaust particles induces anxiogenic effects on male offspring via chronic activation of serotonergic neuron in dorsal raphe nucleus.
Diesel exhaust consists of diesel exhaust particles (DEPs) and gaseous compounds. Because previous research suggested that in utero exposure to DEPs affected spatial learning and memory in male offspring, while epidemiological evidence suggested disturbances in affect after prenatal exposure to particulates, we hypothesized that DEP exposure during pregnancy might also disturb affect. Here, we explored the effects of in utero exposure to DEPs on anxiety 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 assessed anxiety in 6 week-old male offspring using the hole board test and elevated plus maze test. After the behavioral tests, animals were sacrificed and serotonin (5-HT) levels in the dorsal raphe nucleus (DRN) were measured using HPLC. Mice exposed to DEPs in utero demonstrated increased anxiety in both behavioral tests. HPLC analysis revealed a significant increase in 5-HT levels in the DRN. Double immunolabeling of the DRN using anti-5-HT and anti-FosB (a chronic neuronal activation marker) antibodies indicated chronic activation of the DRN might underlie the increased anxiety after prenatal DEP exposure.
The Center for Environmental Health Science for the Next Generation, Research Institute for Science and Technology, Organization for Research Advancement, Tokyo University of Science.
Satoshi
S
Yokota
Shigeru
S
Oshio
Ken
K
Takeda
D000367:Age Factors; D000818:Animals; D001007:Anxiety / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D065847:Dorsal Raphe Nucleus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D005865:Gestational Age; D007150:Immunohistochemistry; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008813:Mice, Inbred ICR; D052638:Particulate Matter / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D016760:Proto-Oncogene Proteins c-fos; D059326:Serotonergic Neurons / Q000187:drug effects* / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D015854:Up-Regulation; D001335:Vehicle Emissions / Q000633:toxicity*
C483819:Fosb protein, mouse; D052638:Particulate Matter; D016760:Proto-Oncogene Proteins c-fos; D001335:Vehicle Emissions; D012701:Serotonin