Environmental toxicants in the brain: A review of astrocytic metabolic dysfunction

Exposure to environmental toxicants is linked to long-term adverse outcomes in the brain and involves the dysfunction of glial and neuronal cells. Astrocytes, the most numerous cell type, are increasingly implicated in the pathogenesis of many diseases of the central nervous system, including neurodegenerative diseases. Astrocytes are critical for proper brain function in part due to their robust antioxidant and unique metabolic capabilities. Additionally, astrocytes are positioned both at the blood-brain barrier, where they are the primary responders to xenobiotic penetrance of the CNS, and at synapses where they are in close contact with neurons and synaptic machinery. While exposure to several classes of environmental toxicants, including chlorinated and fluorinated compounds, and trace metals, have been implicated in neurodegenerative diseases, their impact on astrocytes represents an important and growing field of research. Here, we review existing literature focused on the impact of a range of synthetic compounds on astrocytic function. We focus specifically on perturbed metabolic processes in response to these compounds and consider how perturbation of these pathways impacts disease pathogenesis.