Toxicology of choroid plexus: special reference to metal-induced neurotoxicities.
The chemical stability in the brain underlies normal human thinking, learning, and behavior. Compelling evidence demonstrates a definite capacity of the choroid plexus in sequestering toxic heavy metal and metalloid ions. As the integrity of blood-brain and blood-CSF barriers, both structurally and functionally, is essential to brain chemical stability, the role of the choroid plexus in metal-induced neurotoxicities has become an important, yet under-investigated research area in neurotoxicology. Metals acting on the choroid plexus can be categorized into three major groups. A general choroid plexus toxicant can directly damage the choroid plexus structure such as mercury and cadmium. A selective choroid plexus toxicant may impair specific plexus regulatory pathways that are critical to brain development and function, rather than induce massive pathological alteration. The typical examples in this category include lead-induced alteration in transthyretin production and secretion as well as manganese interaction with iron in the choroid plexus. Furthermore, a sequestered choroid plexus toxicant, such as iron, silver, or gold, may be sequestered by the choroid plexus as an essential CNS defense mechanism. Our current knowledge on the toxicological aspect of choroid plexus research is still incomplete. Thus, the future research needs have been suggested to focus on the role of choroid plexus in early CNS development as affected by metal sequestration in this tissue, to explore how metal accumulation alters the capacity of the choroid plexus in regulation of certain essential elements involved in the etiology of neurodegenerative diseases, and to better understand the blood-CSF barrier as a defense mechanism in overall CNS function.
Zheng
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Division of Environmental Health Sciences, School of Public Health, and Department of Pharmacology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA. wz18@columbia.edu
D000818:Animals; D001151:Arsenic / Q000633:toxicity; D002831:Choroid Plexus / Q000187:drug effects*; D003300:Copper / Q000633:toxicity; D006801:Humans; D007501:Iron / Q000378:metabolism; D007854:Lead / Q000633:toxicity; D020149:Manganese Poisoning / Q000209:etiology; D008628:Mercury / Q000633:toxicity; D008670:Metals / Q000633:toxicity*; D015398:Signal Transduction / Q000187:drug effects; D015262:Xenobiotics / Q000633:toxicity
D008670:Metals; D015262:Xenobiotics; D007854:Lead; D003300:Copper; D007501:Iron; D008628:Mercury; D001151:Arsenic