Traffic-related particulate matter affects behavior, inflammation, and neural integrity in a developmental rodent model

Benjamin C Nephew; Alexandra Nemeth; Neelakshi Hudda; Gillian Beamer; Phyllis Mann; Jocelyn Petitto; Ryan Cali; Marcelo Febo; Praveen Kulkarni; Guillaume Poirier; Jean King; John L Durant; Doug Brugge

doi:10.1016/j.envres.2020.109242

Traffic-related particulate matter affects behavior, inflammation, and neural integrity in a developmental rodent model

Environ Res. 2020 Apr:183:109242. doi: 10.1016/j.envres.2020.109242. Epub 2020 Feb 17.

Authors

Benjamin C Nephew¹, Alexandra Nemeth², Neelakshi Hudda³, Gillian Beamer⁴, Phyllis Mann⁵, Jocelyn Petitto⁶, Ryan Cali⁷, Marcelo Febo⁸, Praveen Kulkarni⁹, Guillaume Poirier¹⁰, Jean King⁷, John L Durant¹¹, Doug Brugge¹²

Affiliations

¹ Worcester Polytechnic Institute, Department of Biology and Biotechnology, 100 Institute Rd, Worcester, MA, 01609, USA; University of Massachusetts Medical School, Department of Psychiatry, 55 N. Lake Road, Worcester, MA, 01655, USA. Electronic address: bcnephew@aol.com.
² Cummings School of Veterinary Medicine, Tufts University, 200 Westboro Road, North Grafton, MA, 01536, USA.
³ Department of Civil and Environmental Engineering, Tufts University, 200 College Avenue, Medford, MA, 02155, USA.
⁴ Cummings School of Veterinary Medicine, Department of Infectious Disease and Global Health, 200 Westboro Road, North Grafton, MA, 01536, USA.
⁵ Cummings School of Veterinary Medicine, Department of Biomedical Sciences, 200 Westboro Road, North Grafton, MA, 01536, USA.
⁶ Worcester Polytechnic Institute, Bioinformatics and Computational Biology Program, 100 Institute Rd, Worcester, MA, 01609, USA.
⁷ Worcester Polytechnic Institute, Department of Biology and Biotechnology, 100 Institute Rd, Worcester, MA, 01609, USA; University of Massachusetts Medical School, Department of Psychiatry, 55 N. Lake Road, Worcester, MA, 01655, USA.
⁸ Department of Psychiatry, University of Florida, Gainesville, FL, 32610, USA.
⁹ Center for Translational NeuroImaging, Northeastern University, Boston, MA, USA.
¹⁰ University of Massachusetts Medical School, Department of Psychiatry, 55 N. Lake Road, Worcester, MA, 01655, USA.
¹¹ Department of Civil and Environmental Engineering, Tufts University, 200 College Avenue, Medford, MA, 02155, USA; Department of Public Health and Community Medicine, Tufts University, 136 Harrison Avenue, Boston, MA, 02111, USA; Jonathan M. Tisch College of Civil Life, Tufts University, 10 Upper Campus Road, Medford, MA, 02155, USA.
¹² Department of Public Health Sciences, University of Connecticut, 195 Farmington Ave., Farmington, CT, 06032, USA.

Abstract

Recent studies indicate that exposure to airborne particulate matter (PM) is associated with cognitive delay, depression, anxiety, autism, and neurodegenerative diseases; however, the role of PM in the etiology of these outcomes is not well-understood. Therefore, there is a need for controlled animal studies to better elucidate the causes and mechanisms by which PM impacts these health outcomes. We assessed the effects of gestational and early life exposure to traffic-related PM on social- and anxiety-related behaviors, cognition, inflammatory markers, and neural integrity in juvenile male rats. Gestating and lactating rats were exposed to PM from a Boston (MA, USA) traffic tunnel for 5 h/day, 5 days/week for 6 weeks (3 weeks gestation, 3 weeks lactation). The target exposure concentration for the fine fraction of nebulized PM, measured as PM2.5, was 200 μg/m³. To assess anxiety and cognitive function, F1 male juveniles underwent elevated platform, cricket predation, nest building, social behavior and marble burying tests at 32-60 days of age. Upon completion of behavioral testing, multiple cytokines and growth factors were measured in these animals and their brains were analyzed with diffusion tensor MRI to assess neural integrity. PM exposure had no effect on litter size or weight, or offspring growth; however, F1 litters developmentally exposed to PM exhibited significantly increased anxiety (p = 0.04), decreased cognition reflected in poorer nest-organization (p = 0.04), and decreased social play and allogrooming (p = 0.003). MRI analysis of ex vivo brains revealed decreased structural integrity of neural tissues in the anterior cingulate and hippocampus in F1 juveniles exposed to PM (p < 0.01, p = 0.03, respectively). F1 juvenile males exposed to PM also exhibited significantly decreased plasma levels of both IL-18 (p = 0.03) and VEGF (p = 0.04), and these changes were inversely correlated with anxiety-related behavior. Chronic exposure of rat dams and their offspring to traffic-related PM during gestation and lactation decreases social behavior, increases anxiety, impairs cognition, decreases levels of inflammatory and growth factors (which are correlated with behavioral changes), and disrupts neural integrity in the juvenile male offspring. Our findings add evidence that exposure to traffic-related air pollution during gestation and lactation is involved in the etiology of autism spectrum disorder and other disorders which include social and cognitive deficits and/or increased anxiety.

Keywords: Behavior; Development; Inflammation; Particulate matter; Rodent.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anxiety* / etiology
Autism Spectrum Disorder* / epidemiology
Boston
Disease Models, Animal
Female
Inflammation
Lactation
Male
Nervous System* / drug effects
Particulate Matter* / toxicity
Rats
Rodentia
Social Behavior
Vehicle Emissions* / toxicity

Substances

Particulate Matter
Vehicle Emissions

Abstract

Publication types

MeSH terms

Substances

Grants and funding