Perinatal exposure to concentrated ambient particulates results in autism-like behavioral deficits in adult mice

Abstract

Exposure to fine ambient particulates (PM) during gestation or neonatally has potent neurotoxic effects. While biological and behavioral data indicate a vulnerability to environmental pollutants across distinct neurodevelopmental windows, the behavioral consequences following exposure across the entire developmental period remain unknown. Moreover, several epidemiological studies support a link between developmental exposure to air pollution and an increased risk of later receiving a diagnosis of autism spectrum disorders (ASD), a neurodevelopmental disorder that persists throughout life. In the current study we sought to determine whether perinatal exposure to PM would reduce sociability and increase repetitive deficits in mice, two hallmark characteristics of ASD. Pregnant female BCF mice were exposed daily to concentrated ambient PM (CAPs) (135.8μg/m) or filtered air (3.1μg/m) throughout gestation followed by additional exposures to both dams and their litters from days 2-10 postpartum. Adult offspring were subsequently assessed for social and repetitive behaviors at 20 weeks of age. Daily perinatal exposure to CAPs significantly decreased sociability in male and female mice as measured by the social approach task; however, reductions in reciprocal social interaction and increased grooming behavior were only present in male offspring exposed to CAPs. These findings demonstrate that exposure to particulate air pollutants throughout early neurodevelopment induces long lasting behavioral deficits in a sex-dependent manner and may be an underlying cause of neurodevelopmental disorders such as ASD.

Effects of PM2.5 and gases exposure during prenatal and early-life on autism–like phenotypes in male rat offspring

“…The open field test showed that there were no differences between the PGE, GE, and even the ALM rats with the control rats (CAE) in motor activity. Our findings are in agreement with two recent studies by Chang et al [14] and Church et al [58]. Previous studies had suggested that the oxidative stress due to the biological enzyme activity caused by exposure to PM 2.5 drives such behavioral changes [59].…”

“…However, during the social novelty phase, the ALM and PGE rats showed no preference when presented to the novel and familiar rats, suggesting the inability to differentiate social novelty that has been reported to be an autism-like behavior [14,57]. Our findings in this test were also in agreement with the studies of Li et al [9] and Church et al [58] that showed an inability to differentiate social novelty.…”

Neuroinflammatory and Behavioral Outcomes Measured in Adult Offspring of Mice Exposed Prenatally to E-Cigarette Aerosols

“…Several studies have reported the presence of fine and ultra-fine PM in e-cigarette aerosols (Ingebrethsen et al 2012;Melstrom et al 2017;Zhao et al 2016), as well as carbonyls, volatile organic compounds, and metals (Cheng 2014; Wagner et al 2018). Although we were not able to specifically define the PM composition generated from the e-cigarette aerosols in this study, a previous report from our laboratories demonstrated behavioral alterations in response to maternal PM 2:5 exposure (Church et al 2018). Therefore, we cannot rule out a potential contribution of these particles in shaping the behavioral and neuroimmunological differences observed in the offspring of e-cigarette-exposed dams.…”

“…Twenty-seven female CD-1 mice, 8-10 weeks of age (Charles River Laboratories), were individually paired at proestrus with adult males and checked the following morning for the presence of a seminal plug (Blum et al 2012;Church et al 2018). Mice were housed in cages with high-efficiency particulate air (HEPA)-filtered lids and were provided free access to food and water at the New York University (NYU) Department of Environmental Medicine animal facility and, subsequently, in the same manner at Mount Holyoke College (Massachusetts).…”

Avaliação dos efeitos da exposição pré e pós-natal à poluição atmosférica no sistema nervoso central de camundongos

“…Nesse sentido, estudos têm demostrado que a exposição gestacional a poluentes ambientais causa aumento de citocinas pró-inflamatórias, de ciclooxigenase 2 (COX-2), de proteína glial fibrilar ácida (GFAP, marcador de astrócitos ativados), de proteína adaptadora ligante de cálcio ionizado 1 (IBA-1, marcador de micróglia ativa) no cérebro de camundongos (Kulas et al, 2018;Umezawa et al, 2018). Church et al, (2018) evidenciaram que a exposição no período gestacional até o 10º dia pós-natal a uma concentração de 135,8 µg/m³ de MP 2.5 causou alterações de maneira sexo-dependente que perduraram na vida dos animais, sendo que as alterações estão relacionadas a déficits comportamentais semelhantes ao autismo.…”