title: Effect of the environmental pollutant hexachlorobenzene (HCB) on the neuronal differentiation of mouse embryonic stem cells.
abstract: Exposure to persistent environmental pollutants may constitute an important factor on the onset of a number of neurological disorders such as autism, Parkinson's disease, and Attention Deficit Disorder (ADD), which have also been linked to reduced GABAergic neuronal function. GABAergic neurons produce γ-aminobutyric acid (GABA), which is the main inhibitory neurotransmitter in the brain. However, the lack of appropriate models has hindered the study of suspected environmental pollutants on GABAergic function. In this work, we have examined the effect of hexachlorobenzene (HCB), a persistent and bioaccumulative environmental pollutant, on the function and morphology of GABAergic neurons generated in vitro from mouse embryonic stem (ES) cells. We observed that: (1) treatment with 0.5 nM HCB did not affect cell viability, but affected the neuronal differentiation of ES cells; (2) HCB induced the production of reactive oxygen species (ROS); and (3) HCB repressed neurite outgrowth in GABAergic neurons, but this effect was reversed by the ROS scavenger N-acetylcysteine (NAC). Our study also revealed that HCB did not significantly interfere with the function of K+ ion channels in the neuronal soma, which indicates that this pollutant does not affect the maturation of the GABAergic neuronal soma. Our results suggest a mechanism by which environmental pollutants interfere with normal GABAergic neuronal function and may promote the onset of a number of neurological disorders such as autism and ADD.
authors.affiliation: Department of Biological Sciences and Environmental Toxicology Program, Southern University and A&M College, Baton Rouge, LA 70813, USA. eduardo_martinez@sube.edu.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Addae
authors.forename: Henrique
authors.initials: H
authors.lastname: Cheng
authors.forename: Eduardo
authors.initials: E
authors.lastname: Martinez-Ceballos
mesh_terms: D000111:Acetylcysteine; D000818:Animals; D015415:Biomarkers; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects*; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000633:toxicity*; D059330:GABAergic Neurons / Q000187:drug effects; D005786:Gene Expression Regulation; D006581:Hexachlorobenzene / Q000008:administration & dosage / Q000633:toxicity*; D051379:Mice; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015415:Biomarkers; D004785:Environmental Pollutants; D012333:RNA, Messenger; D006581:Hexachlorobenzene; D000111:Acetylcysteine