Exposure to diesel exhaust during fetal period affects behavior and neurotransmitters in male offspring mice

Yokota, Satoshi; Moriya, Nozomu; Iwata, Mari; Umezawa, Masakazu; Oshio, Shigeru; Takeda, Ken

doi:10.2131/jts.38.13

Cited by 68 publications

(52 citation statements)

References 35 publications

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“…The maternal environment is very important in the development of the offspring, as several "critical periods" of central nervous system development occur during gestation. Our previous work demonstrated that prenatal exposure to DE affected locomotion Yokota et al, 2013b;Yokota et al, 2009) and aggressive behavior (Yokota et al, 2016) in male offspring, and that prenatal exposure to DEPs (the same exposure as was used herein) impaired learning and memory, also in male offspring (Yokota et al, 2015).…”

Section: Discussionmentioning

confidence: 74%

“…Rodent models employing in utero exposure to DE or DEPs showed various postnatal consequences, including pathological effects on the cerebral cortex (Sugamata et al, 2006), decreased spontaneous motor activity Yokota et al, 2009), dysfunction of motor coordination and induced impulsivity (Yokota et al, 2013b), and impairment of learning and memory (Yokota et al, 2015) of male offspring. However, despite DEPs being a major contributor to airborne PM, there have been no studies on whether in utero exposure to DE affects anxiety levels of offspring.…”

Section: Introductionmentioning

confidence: 99%

“…However, despite DEPs being a major contributor to airborne PM, there have been no studies on whether in utero exposure to DE affects anxiety levels of offspring. Our previous study demonstrated that in utero exposure to high concentrations of DE altered serotonin (5-HT) levels in various brain regions (Yokota et al, 2013b) of male offspring. Such alterations could induce anxiety or other behavioral disturbances in the next generation (i.e., the offspring of the exposed dam).…”

Section: Introductionmentioning

confidence: 99%

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<i>In utero</i> exposure to diesel exhaust particles induces anxiogenic effects on male offspring via chronic activation of serotonergic neuron in dorsal raphe nucleus

2016

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-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.

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Section: Discussionmentioning

confidence: 74%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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<i>In utero</i> exposure to diesel exhaust particles induces anxiogenic effects on male offspring via chronic activation of serotonergic neuron in dorsal raphe nucleus

2016

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“…A subsequent study has shown that prenatal exposure to DE (at 1.0 mg DEP/m 3 ) decreased dopamine turnover, which is an index of dopamine neuronal activity, in the striatum (Yokota et al, 2009). Behavioral changes related to monoamine in response to maternal inhalation of DE are also reported (Yokota et al, 2013). The exposure of mice in utero to 171 μg DEP/m 3 of DE decreases spontaneous locomotor activity and alters neurochemical monoamine metabolism in several brain regions (Suzuki et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Fetal exposure to diesel exhaust affects X-chromosome inactivation factor expression in mice

et al. 2013

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-Several studies have shown effects of diesel exhaust (DE) on the central nervous system, but the mechanism is unclear. Fetal mice were exposed to whole DE (contains gases and particles) in an inhalation chamber, and cerebrum gene expression changes were examined by gene assay (microarray and quantitative real-time PCR). By microarray, upregulation of Xist, B-raf and Drwms2 were detected. Especially, mRNA expression of Xist was increased in a concentration-dependent manner in male and female mice. Xist (X-inactive specific transcript) is a major effector of the X-inactivation process, and X-linked genes are highly expressed in brain tissue and consistent with a role in brain developments. By quantitative real-time PCR, Tsix (crucial noncoding antisense partner of Xist) and other X-linked genes (Mecp2, Hprt1, and Sts) were examined; Tsix was upregulated, and other X-linked genes were unaffected in the male and female mice. Our findings suggest that exposure to DE increases Xist and Tsix gene expression in utero without influencing X-linked gene expression. An examination of Xist gene expression changes may provide an important biomarker for DE-induced effects. The possibility of avoiding X-chromosome inactivation (XCI) mechanisms by minimizing exposure to DE is expected.

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“…A similar exposure regimen applied on GD 2-16 and again on PND 0-16 altered the levels of mRNA encoding for proteins involved in reaction to chemically induced stress (including oxidative stress) and endocrine regulation in both sexes as measured during lactation [108]. Prenatal exposure to whole DE have been shown to reduce spontaneous motor activity, impair motor coordination and function of monoaminergic systems in various brain regions, and induce impulsive behavior [116][117][118]. DEP exposure (1000 g/m 3 ) during pregnancy and nursing increased locomotor activity, self-grooming in the presence of an unfamiliar mouse, and rearing behavior in the adult male offspring [119].…”

Section: Nervous Systemmentioning

confidence: 99%

A perspective on the developmental toxicity of inhaled nanoparticles

Hougaard

Campagnolo

Chavatte‐Palmer

et al. 2015

Reproductive Toxicology

158

126

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This paper aimed to clarify whether maternal inhalation of engineered nanoparticles (NP) may constitute a hazard to pregnancy and fetal development, primarily based on experimental animal studies of NP and air pollution particles. Overall, it is plausible that NP may translocate from the respiratory tract to the placenta and fetus, but also that adverse effects may occur secondarily to maternal inflammatory responses. The limited database describes several organ systems in the offspring to be potentially sensitive to maternal inhalation of particles, but large uncertainties exist about the implications for embryo-fetal development and health later in life. Clearly, the potential for hazard remains to be characterized. Considering the increased production and application of nanomaterials and related consumer products a testing strategy for NP should be established. Due to large gaps in data, significant amounts of groundwork are warranted for a testing strategy to be established on a sound scientific basis.

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Exposure to diesel exhaust during fetal period affects behavior and neurotransmitters in male offspring mice

Cited by 68 publications

References 35 publications

<i>In utero</i> exposure to diesel exhaust particles induces anxiogenic effects on male offspring via chronic activation of serotonergic neuron in dorsal raphe nucleus

<i>In utero</i> exposure to diesel exhaust particles induces anxiogenic effects on male offspring via chronic activation of serotonergic neuron in dorsal raphe nucleus

Fetal exposure to diesel exhaust affects X-chromosome inactivation factor expression in mice

A perspective on the developmental toxicity of inhaled nanoparticles

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