Astrocytes as targets of lower chlorinated biphenyls

Polychlorinated biphenyls (PCBs) are man-made industrial chemicals which are difficult to degrade and remain in the environment for decades. Commercial production of PCBs was banned in the United States in 1979, however, their unintentional production continues to this day. The ongoing unintentional production mainly comprises lower chlorinated biphenyls, that is, PCBs having four or less Chlorine atom substitutions. Exposure to such persistent industrial chemicals is associated with various adverse health effects including neurotoxic outcomes such as cognitive dysfunction, autism spectrum disorders, and Parkinson’s disease. However, the underlying mechanisms of how PCBs bring about these neurotoxic effects are not yet fully understood. Most of the research has been focused on using neurons as the model system. However, we now know that there are multiple cell types in the brain, each carrying out a unique set of functions to maintain normal brain health. Astrocytes, the most abundant glial cell type of the brain, are required for maintaining normal neuronal health and brain function. They can also become reactive and play a protective or damaging role when stressed. We think that because of such unique functions astrocytes have, it is necessary to study whether astrocytes get adversely affected due to PCBs and the mechanisms that may be underlying the neurotoxic outcomes. In this study we have evaluated the toxicity of lower chlorinated biphenyls.

We found that astrocytes are susceptible to lower chlorinated biphenyl exposure. Among the four lower chlorinated biphenyls studied along with their human-relevant metabolites, PCB52 was found to be the most toxic compound, along with its human-relevant metabolites. In addition, magnitude of toxicity is different between the parent PCB and its human-relevant metabolites. The mitochondria, commonly referred to as the 'powerhouse of the cell', were also found to be impaired in astrocytes, both in their structure and function. These findings for the first time suggest that astrocytes are a sensitive target of PCBs and delve into mechanisms associated with impaired astrocyte health. Further mechanistic studies would need to include other glial cell types of the brain, along with neurons, to fully understand the mechanisms of PCB-induced neurotoxicity.