Developmental Exposure to Concentrated Ambient Particles and Preference for Immediate Reward in Mice

Abstract

Background: Recent epidemiological studies indicate negative associations between a diverse group of air pollutants and cognitive functioning in children and adults, and aspects of attention deficit in children. Neuroinflammation and oxidative stress are two putative biological mechanisms by which air pollutants may adversely affect the brain.Objectives: We sought to determine whether exposure to concentrated ambient particulate matter (CAPS) during the first 2 weeks of life, alone or again in adulthood, could alter responding for delayed reward, a critical component of human decision making. Greater preference for immediate reward has been implicated as a component of several psychiatric disorders, addiction, obesity, and attention deficit.Methods: C57BL/6J mice were exposed to ultrafine particles (< 100 nm in aerodynamic diameter; CAPS) using the Harvard University Concentrated Ambient Particle System (HUCAPS) or filtered air in the postnatal period (days 4–7 and 10–13) with and without adult exposure over days 56–60. In adulthood, delay behavior was assessed using a fixed-ratio waiting-for-reward (FR wait) paradigm in which 25 responses (FR25) were required to initiate the waiting-for-reward component during which mice obtained “free” sucrose pellets with the stipulation that these “free” pellets were delivered at increasing delay intervals.Results: Coupled with increased FR response rates, mice exposed to postnatal CAPS displayed increased FR resets that reinstated short delays, indicating a preference for shorter delays, despite the added response cost of the FR25. No associated changes in locomotor activity were observed.Conclusions: Postnatal CAPS exposure produces an enhanced bias towards immediate rewards, a risk factor for several central nervous system (CNS) disorders. This enhancement does not appear to be the result of hyperactivity. The findings underscore the need for further evaluation of air pollution effects on the CNS and its potential contribution to CNS diseases and disorders.

Developmental neurotoxicity of inhaled ambient ultrafine particle air pollution: Parallels with neuropathological and behavioral features of autism and other neurodevelopmental disorders

“…However, the time between each successive free reward delivery doubled during the wait component, thus requiring increasingly longer wait times, and any lever press response during the waiting component re-set the 25 response requirement to re-start the wait component. Postnatal CAPS markedly decreased mean waiting time and increased numbers of fixed ratio resets in males, despite the added cost in terms of numbers of responses required for each reward delivery [79]. Fig.…”

“…Mice were co-housed for 3 days and bred monogamously, after which males were removed and pregnant dams were singly housed with litters until weaning on PND21. Pups were exposed to filtered air (Air) or c oncentrated a mbient ultrafine p articles (CAPS) using the Harvard University Concentrated Ambient Particle System (HUCAPS) fitted with a size-selective inlet and a high-volume ultrafine particle (UFPs, ≤100nm) concentrator (10-20×) that takes in outdoor air at 5000 liters per minute and concentrates ambient UFP, as previously described [79-82]. Exposures lasted for 4 hours per day from 0700-1200 for 4 days per week from PND4-7 and PND10-13, with exposure timing corresponding to peak vehicular traffic outside the intake valve of the HUCAPS instrumentation.…”

“…Y axis response counter resets to baseline after each 30 responses; pips (backslashes) = reward delivery, horizontal lines = periods of waiting, vertical lines = FR responding. Modified from [79]. …”

Prenatal and childhood traffic-related air pollution exposure and childhood executive function and behavior

“…Adult volunteers given experimental short-term exposures to diesel exhaust displayed changes in frontal cortex brain activity, suggesting a stress response in that region of the brain (Cruts et al 2008). Mice experimentally exposed to ultrafine particles (aerodynamic diameter <100 nm) at environmentally-relevant concentrations in the postnatal period showed greater preference for immediate reward, which may be an indicator of impulsivity (Allen et al 2013); exposed mice were also observed to have alterations in neurotransmitter levels, including increased glutamate in the frontal cortex, which investigators postulated could indicate an excitotoxic mechanism of particulate air pollution in the brain (Allen et al 2014). …”

Echoes of Autism? Inhaled Ultrafine Particles and Brain Changes in Mice

“…It’s time to consider that possibility,” says first author Joshua Allen, an assistant research professor at URMC. In other mouse studies, the URMC team has reported that inhaling ultrafine particles was also associated with changes in behavior 8 and memory 9 indicating impaired neurodevelopment.…”