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Acute exposure to diesel exhaust impairs adult neurogenesis in mice: prominence in males and protective effect of pioglitazone

  • Organ Toxicity and Mechanisms
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Abstract

Adult neurogenesis is the process by which neural stem cells give rise to new functional neurons in specific regions of the adult brain, a process that occurs throughout life. Significantly, neurodegenerative and psychiatric disorders present suppressed neurogenesis, activated microglia, and neuroinflammation. Traffic-related air pollution has been shown to adversely affect the central nervous system. As the cardinal effects of air pollution exposure are microglial activation, and ensuing oxidative stress and neuroinflammation, we investigated whether acute exposures to diesel exhaust (DE) would inhibit adult neurogenesis in mice. Mice were exposed for 6 h to DE at a PM2.5 concentration of 250–300 μg/m3, followed by assessment of adult neurogenesis in the hippocampal subgranular zone (SGZ), the subventricular zone (SVZ), and olfactory bulb (OB). DE impaired cellular proliferation in the SGZ and SVZ in males, but not females. DE reduced adult neurogenesis, with male mice showing fewer new neurons in the SGZ, SVZ, and OB, and females showing fewer new neurons only in the OB. To assess whether blocking microglial activation protected against DE-induced suppression of adult hippocampal neurogenesis, male mice were pre-treated with pioglitazone (PGZ) prior to DE exposure. The effects of DE exposure on microglia, as well as neuroinflammation and oxidative stress, were reduced by PGZ. PGZ also antagonized DE-induced suppression of neurogenesis in the SGZ. These results suggest that DE exposure impairs adult neurogenesis in a sex-dependent manner, by a mechanism likely to involve microglia activation and neuroinflammation.

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Acknowledgements

This study was supported in part by grants from the National Institute of Environmental Health Sciences (R01ES22949, R01ES28273, P30ES07033), the National Institute of Child Health and Human Development (U54HD083091), and by funds from the Department of Environmental and Occupational Health Sciences, University of Washington. Thanks are due to Mr. James Stewart, who oversaw diesel exhaust exposures, the members of Dr. Lucio G. Costa’s and Dr. Zhengui Xia’s laboratory for their assistance in troubleshooting and helpful discussions, and Dr. Jennifer Stone and Mr. Glen McDonald at the Center on Human Development and Disability for their help with fluorescence microscopy and immunohistochemistry.

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  1. Department of Environmental and Occupational Health Sciences, University of Washington, 4225 Roosevelt, Suite No. 100, Seattle, WA, 98105, USA

    Jacki L. Coburn, Toby B. Cole, Khoi T. Dao & Lucio G. Costa

  2. Center on Human Development and Disability, University of Washington, Seattle, WA, USA

    Toby B. Cole

  3. Department of Medicine and Surgery, University of Parma, Parma, Italy

    Lucio G. Costa

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  1. Jacki L. Coburn
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Correspondence to Toby B. Cole or Lucio G. Costa.

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C57BL6/J mice of both sexes were used in these studies. All animal procedures were pre-approved by the University of Washington Institutional Animal Care and Use Committee (IACUC), Protocol 2077-14. Experiments were carried out in accordance with the National Research Council Guide for the Care and Use of Laboratory Animals, as adopted by the National Institutes of Health.

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Coburn, J.L., Cole, T.B., Dao, K.T. et al. Acute exposure to diesel exhaust impairs adult neurogenesis in mice: prominence in males and protective effect of pioglitazone. Arch Toxicol 92, 1815–1829 (2018). https://doi.org/10.1007/s00204-018-2180-5

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