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.

The Redox Function of APE1 Is Involved in the Differentiation Process of Stem Cells toward a Neuronal Cell Fate

“…Last, the addition of E3330 to differentiating cells modifies the expression of markers of specific neuronal subtypes, increasing the expression of cholinergic, dopaminergic and GABAergic markers. These results may be consistent with the observed effect of mild hypoxia on neural progenitor cell differentiation towards a dopaminergic phenotype [41] or with the effects of pollutants that increase intracellular ROS levels on the maturation of GABAergic neurons [42] . Less prominent are the effects observed on the expression of glutamatergic or serotoninergic markers.…”

Levels and predictors of persistent organic pollutants in an adult population from four Spanish regions

“…Hexachlorobenzene (HCB) was previously used as fungicide for cereals (Addae et al, 2013) and is still released during the burning of waste and in chloralkali and wood-preserving processes, among other industrial processes (ATSDR, 1996;Aurrekoetxea Agirre et al, 2011). The half-life of HCB in the human body has been estimated at around 6 years (Hardell et al, 2010;Mrema et al, 2013).…”

Individual variation of persistent organic pollutants in relation to stable isotope ratios, sex, reproductive phase and oxidative status in Scopoli's shearwaters ( Calonectris diomedea ) from the Southern Mediterranean

“…A recent meta-analysis showed that oxidative stress is a unifying mechanism underlying the toxicity of anthropogenic pollution including heavy metals, polycyclic aromatic hydrocarbons, or nitrogen-oxides (Isaksson, 2010). Although this meta-analysis showed that the effect size for SOD was moderate, previous mechanistic work showed that contaminants like HCB may increase free radical production and oxidative stress (Addae et al, 2013). Overall, our data suggest that POP concentrations in shearwaters did not have a strong impact on the regulation of blood oxidative balance or, generally, on the health status of birds.…”