title: Human brain derived cells respond in a type-specific manner after exposure to urban particulate matter (PM).
abstract: Exposure to particulate matter (PM), a component of urban air pollution, may cause adverse effects in the brain. Although the exact mechanisms involved are unknown, both oxidative and inflammatory responses have been reported. Since the main route of exposure to particulate matter is through inhalation, there is a potential for compounds to directly enter the brain and alter normal cellular function. Enhancement in both oxidative stress and neuroinflammatory markers has been observed in neurodegenerative disorders and PM-induced potentiation of these events may accelerate the disease process. The objective of this pilot study was to use normal human brain cells, a model system which has not been previously used, to assess cell-type-specific responses after exposure to ultrafine particles (UFP). Human microglia, neurons, and astrocytes were grown separately or as co-cultures and then exposed to aqueous UFP suspensions. Reactive Oxygen Species (ROS) formation and the proinflammatory cytokine tumor necrosis factor alpha (TNF-α) were measured as markers of oxidative stress or inflammation respectively. Our results revealed that after exposure to 2 μg/ml of particles, normal human neurons exhibit a decrease in ROS formation and an increase in TNF-α. The observed decrease in ROS formation persisted in the presence of glial cells, which contrasts previous studies done in rodent cells reporting that PM-induced microglial activation modulates neuronal responses. Our study indicates that human CNS cells may respond differently compared to rodent cells and that their use may be more predictive in risk assessment.
authors.affiliation: Department of Pharmaceutical Sciences, Western University of Health Sciences, Pomona, CA, United States. Electronic address: acampbell@westernu.edu.
authors.forename: Arezoo
authors.initials: A
authors.lastname: Campbell
authors.affiliation: Department of Civil & Environmental Engineering, University of Southern California, Los Angeles, CA, United States.
authors.forename: Nancy
authors.initials: N
authors.lastname: Daher
authors.affiliation: Department of Pharmaceutical Sciences, Western University of Health Sciences, Pomona, CA, United States.
authors.forename: Parrisa
authors.initials: P
authors.lastname: Solaimani
authors.affiliation: Department of Pharmaceutical Sciences, Western University of Health Sciences, Pomona, CA, United States.
authors.forename: Kriscelle
authors.initials: K
authors.lastname: Mendoza
authors.affiliation: Department of Civil & Environmental Engineering, University of Southern California, Los Angeles, CA, United States.
authors.forename: Constantinos
authors.initials: C
authors.lastname: Sioutas
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D001921:Brain / Q000166:cytology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D006801:Humans; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D052638:Particulate Matter / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000393:Air Pollutants; D052638:Particulate Matter; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha
keywords: Astrocytes; Microglia; Neurons; Reactive oxygen species; Tumor necrosis factor alpha (TNF-α); Ultrafine particles (UFP)