Concentrated ambient fine particulate matter (PM2.5) exposure induce brain damage in pre and postnatal exposed mice

• Published in: Neurotoxicology (Park Forest South) Vol. 79; pp. 127 - 141
• Main Authors: Di Domenico, Marlise, Benevenuto, Sarah Gomes de Menezes, Tomasini, Paula Pellenz, Yariwake, Victor Yuji, de Oliveira Alves, Nilmara, Rahmeier, Francine Luciano, da Cruz Fernandes, Marilda, Moura, Dinara Jaqueline, Nascimento Saldiva, Paulo Hilário, Veras, Mariana Matera
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-07-2020; Elsevier BV; Elsevier
• Subjects: Air pollution; Air pollution measurements; Ambient particle matter; Astrocytes; Behavior; Brain; Brain damage; Brain injury; Brain volume; Brain-derived neurotrophic factor; Central nervous system; Corpus callosum; Cytotoxicity; Dentate gyrus; Exposure; Gene expression; Genomic instability; Glial activation; Glial cells; Hippocampus; Life Sciences; Locomotor activity; Microglia; Micronuclei; Neuronal-glial interactions; Neurotoxicity; Outdoor air quality; Oxidative stress; Particulate matter; Pollutants; Prenatal experience; Public health; Serotonin; Serotonin receptors; Urban planning; γ-Aminobutyric acid; Brain volume; Ambient particle matter; Glial activation; Neurotoxicity; Behavior; neurotoxicity; behavior; brain volume; ambient particle matter; glial activation
• ISSN: 0161-813X; 1872-9711
• DOI: 10.1016/j.neuro.2020.05.004

•Prenatal exposure to PM2.5 is associated with an anxiolytic behavior in adult offspring.•Prenatal exposure to PM2.5 reduced the corpus callosum (CC) volume in adult offspring.•Male PM2.5-exposed mice showed increased glial activation in the cortex, CC, C1A, and dentate gyrus.•Pre and postnatally exposed mice to PM2.5 decreased BDNF expression in the hippocampus.•Ambient PM2.5 exposure induced genomic stability in C6 cells in a non-cytotoxic dose.
Air pollution is a public health concern that has been associated with adverse effects on the development and functions of the central nervous system (CNS). However, studies on the effects of exposure to pollutants on the CNS across the entire developmental period still remain scarce. In this study, we investigated the impacts of prenatal and/or postnatal exposure to fine particulate matter (PM2.5) from São Paulo city, on the brain structure and behavior of juvenile male mice. BALB/c mice were exposed to PM2.5 concentrated ambient particles (CAP) at a daily concentration of 600 μg/m³ during the gestational [gestational day (GD) 1.5–18.5] and the postnatal periods [postnatal day (PND) 22–90] to filtered air (FA) in both periods (FA/FA), to CAP only in the postnatal period (FA/CAP), to CAP only in the gestational period (CAP/FA), and to CAP in both periods (CAP/CAP). Behavioral tests were performed when animals were at PND 30 and PND 90. Glial activation, brain volume, cortical neuron number, serotonergic and GABAergic receptors, as well as oxidative stress, were measured. Mice at PND 90 presented greater behavioral changes in the form of greater locomotor activity in the FA-CAP and CAP-CAP groups. In general, these same groups explored objects longer and the CAP-FA group presented anxiolytic behavior. There was no difference in total brain volume among groups, but a lower corpus callosum (CC) volume was observed in the CAP-FA group. Also, the CAP-CAP group presented an increase in microglia in the cortex and an increased in astrocytes in the cortex, CC, and C1A and dentate gyrus of hippocampus regions. Gene expression analysis showed a decrease in BDNF in the hippocampus of CAP-CAP group. Treatment of immortalized glial cells with non-cytotoxic doses of ambient PM2.5 increased micronuclei frequencies, indicating genomic instability. These findings highlight the potential for negative neurodevelopmental outcomes induced by exposure to moderate levels of PM2.5 in Sao Paulo city.