Astrocyte-mediated methylmercury neurotoxicity.
Methylmercury (MeHg) is a potent neurotoxicant. Any source of environmental mercury represents a potential risk for human MeHg poisoning, because the methylation of inorganic mercury to MeHg in waterways results ultimately in its accumulation in the sea food chain, which represents the most prevalent source for human consumption. A small amount of MeHg accumulates in the central nervous system (CNS), particularly in astrocytes. Astrocytic swelling, excitatory amino acid (EAA) release and uptake inhibition, as well as EAA transporter expression inhibition are known sequelae of MeHg exposure. Herein, we review the effect of MeHg on additional transport systems (for cystine and cysteine) as well as arachidonic acid (AA) release and cytosolic phospholipase A2 (cPLA2) regulation and attempt to integrate the effects of MeHg in astrocytes within a mechanistic hypothesis that explains the inability of these cells to maintain control of the proper milieu of the extracellular fluid and, in turn, leads to neuronal demise.
Shanker
Gouri
G
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA.
Syversen
Tore
T
Aschner
Michael
M
D000818:Animals; D016718:Arachidonic Acid / Q000096:biosynthesis; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D003545:Cysteine / Q000037:antagonists & inhibitors / Q000378:metabolism; D003553:Cystine / Q000037:antagonists & inhibitors / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D020262:Mercury Poisoning, Nervous System / Q000378:metabolism* / Q000473:pathology; D008767:Methylmercury Compounds / Q000633:toxicity*; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2
D008767:Methylmercury Compounds; D016718:Arachidonic Acid; D003553:Cystine; D010741:Phospholipases A; D054467:Phospholipases A2; D005978:Glutathione; D003545:Cysteine