title: Exposure to ambient ultrafine particulate matter alters the expression of genes in primary human neurons.
abstract: Exposure to ambient particulate matter (PM) has been associated with the onset of neurodevelopmental and neurodegenerative disorders, but the mechanism of toxicity remains unclear. To gain insight into this neurotoxicity, this study sought to examine global gene expression changes caused by exposure to ambient ultrafine PM. Microarray analysis was performed on primary human neurons derived from fetal brain tissue after a 24h exposure to 20μg/mL of ambient ultrafine particles. We found a majority of the changes in noncoding RNAs, which are involved in epigenetic regulation of gene expression, and thereby could impact the expression of several other protein coding gene targets. Although neurons from biologically different lot numbers were used, we found a significant increase in the expression of metallothionein 1A and 1F in all samples after exposure to particulate matter as confirmed by quantitative PCR. These metallothionein 1 proteins are responsible for neuroprotection after exposure to environmental insult but prolonged induction can be toxic. Epidemiological studies have reported that in utero exposure to ultrafine PM not only leads to neurodevelopmental and behavioral abnormalities, but may also predispose the progeny to neurodegenerative disease later in life by genetic imprinting. Our results pinpoint some of the PM-induced genetic changes that may underlie these findings.
authors.affiliation: Department of Pharmaceutical Sciences, Western University of Health Sciences, Pomona, CA, USA.
authors.forename: Parrisa
authors.initials: P
authors.lastname: Solaimani
authors.affiliation: Department of Civil and Environmental Engineering, University of Southern California, Los Angeles, CA, USA.
authors.forename: Arian
authors.initials: A
authors.lastname: Saffari
authors.affiliation: Department of Civil and Environmental Engineering, University of Southern California, Los Angeles, CA, USA.
authors.forename: Constantinos
authors.initials: C
authors.lastname: Sioutas
authors.affiliation: Center for Occupational and Environmental Health, Department of Medicine, University of California, Irvine, CA, USA.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Bondy
authors.affiliation: Department of Pharmaceutical Sciences, Western University of Health Sciences, Pomona, CA, USA. Electronic address: acampbell@westernu.edu.
authors.forename: Arezoo
authors.initials: A
authors.lastname: Campbell
mesh_terms: D000255:Adenosine Triphosphate; D001921:Brain / Q000166:cytology; D002478:Cells, Cultured; D005333:Fetus; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism*; D046228:Microarray Analysis; D009474:Neurons / Q000187:drug effects*; D052638:Particulate Matter / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D022661:RNA, Untranslated / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D052638:Particulate Matter; D012333:RNA, Messenger; D022661:RNA, Untranslated; D014409:Tumor Necrosis Factor-alpha; D000255:Adenosine Triphosphate; D008668:Metallothionein
keywords: Air pollution; Genetic imprinting; Human neurons; Metallothionein; Neurodevelopment; Noncoding RNA; Ultrafine particulate matter