In utero exposure to fine particulate matter results in an altered neuroimmune phenotype in adult mice

Abstract

Environmental exposure to air pollution has been linked to a number of health problems including organ rejection, lung damage and inflammation. While the deleterious effects of air pollution in adult animals are well documented, the long-term consequences of particulate matter (PM) exposure during animal development are uncertain. In this study we tested the hypothesis that environmental exposure to PM 2.5 μm in diameter in utero promotes long term inflammation and neurodegeneration. We evaluated the behavior of PM exposed animals using several tests and observed deficits in spatial memory without robust changes in anxiety-like behavior. We then examined how this affects the brains of adult animals by examining proteins implicated in neurodegeneration, synapse formation and inflammation by western blot, ELISA and immunohistochemistry. These tests revealed significantly increased levels of COX2 protein in PM2.5 exposed animal brains in addition to changes in synaptophysin and Arg1 proteins. Exposure to PM2.5 also increased the immunoreactivity for GFAP, a marker of activated astrocytes. Cytokine concentrations in the brain and spleen were also altered by PM2.5 exposure. These findings indicate that in utero exposure to particulate matter has long term consequences which may affect the development of both the brain and the immune system in addition to promoting inflammatory change in adult animals.

Effects of early postnatal exposure to fine particulate matter on emotional and cognitive development and structural synaptic plasticity in immature and mature rats

“…Fonken et al () reported that depressive‐like responses, but not anxiety‐like responses increased in male mice exposed to PM2.5 during adulthood, relative to control mice. Kulas et al () found that PM2.5 perinatal exposure in mice did not cause anxiety‐like behavior in male offspring. Our results suggested that PM2.5 exposure increased anxiety‐like behaviors in immature and mature rats, as shown by a lower percentage of number of entries into open arms or decreased percentage of time spent in open arms.…”

“…Reports on the influence of PM2.5 exposure on structural synaptic plasticity remain contradictory and insufficient. Kulas et al () found that prenatal exposure to PM2.5 in mice led to elevated SYP expression and unchanged PSD95 expression in the hippocampus of male offspring. Zhang et al () reported that prenatal PM2.5 exposure in mice decreased postsynaptic densities of membranes and the number of synaptic vesicles in the cerebral cortex of offspring, and an in vitro study suggested that PM2.5 exposure reduced PSD95 expression in cortical neurons (Chen, Li, & Sang, ).…”

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

“…Em relação ao desenvolvimento neural, estudos relatam que a exposição a partículas finas e ultrafinas durante o período embrionário afeta a maturação de oligodendrócitos e a mielização do cérebro na idade adulta (Klocke et al, 2018). Além disso, alterações comportamentais e patológicas têm sido relacionadas à exposição a partículas ultrafinas durante o desenvolvimento embrionário (Klocke et al, 2017;Kulas et al, 2018).…”

“…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.…”

“…Estudos conduzidos em modelo animal demonstram que a exposição a poluentes como partículas ambientais concentradas, partículas de diesel e residual oil fly ash (ROFA) podem causar alterações comportamentais (Zanchi et al, 2008;Win-Shwe, T.-T., Yamamoto, S., et al, 2012; Allen, J. L., Liu, X., Weston, D., et al, 2014). Em humanos, a exposição à poluição atmosférica tem sido associada ao prejuízo de memória e aumento de incidência de desordens cognitivas (Xu et al, 2016) (Kulas et al, 2018).…”