Developmental exposure to diesel exhaust upregulates transcription factor expression, decreases hippocampal neurogenesis
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(2020) 12:41
RESEARCH
Open Access
Developmental exposure to diesel exhaust upregulates transcription factor expression, decreases hippocampal neurogenesis, and alters cortical lamina organization: relevance to neurodevelopmental disorders Toby B. Cole1,2*† , Yu-Chi Chang1,3†, Khoi Dao1, Ray Daza4,5, Robert Hevner4,5,6 and Lucio G. Costa1,7
Abstract Background: Exposure to traffic-related air pollution (TRAP) during development and/or in adulthood has been associated in many human studies with both neurodevelopmental and neurodegenerative diseases, such as autism spectrum disorder (ASD) and Alzheimer’s disease (AD) or Parkinson’s disease (PD). Methods: In the present study, C57BL/6 J mice were exposed to environmentally relevant levels (250+/−50 μg/m3) of diesel exhaust (DE) or filtered air (FA) during development (E0 to PND21). The expression of several transcription factors relevant for CNS development was assessed on PND3. To address possible mechanistic underpinnings of previously observed behavioral effects of DE exposure, adult neurogenesis in the hippocampus and laminar organization of neurons in the somatosensory cortex were analyzed on PND60. Results were analyzed separately for male and female mice. Results: Developmental DE exposure caused a male-specific upregulation of Pax6, Tbr1, Tbr2, Sp1, and Creb1 on PND3. In contrast, in both males and females, Tbr2+ intermediate progenitor cells in the PND60 hippocampal dentate gyrus were decreased, as an indication of reduced adult neurogenesis. In the somatosensory region of the cerebral cortex, laminar distribution of Trb1, calbindin, and parvalbumin (but not of Ctip2 or Cux1) was altered by developmental DE exposure. Conclusions: These results provide additional evidence to previous findings indicating the ability of developmental DE exposure to cause biochemical/molecular and behavioral alterations that may be involved in neurodevelopmental disorders such as ASD. Keywords: Air pollution, Diesel exhaust, Developmental neurotoxicity, Adult neurogenesis, Cortical lamina organization, Autism spectrum disorder
* Correspondence: [email protected] † Toby B. Cole and Yu-Chi Chang contributed equally to this work. 1 Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA 2 Center on Human Development and Disability, University of Washington, Seattle, WA, USA Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's
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