The marine toxin domoic acid may affect the developing brain by activation of neonatal brain microglia and subsequent neurotoxic mediator generation.
Amnesic shellfish poisoning, one of the shellfish poisoning syndromes, is caused by the marine diatom toxin domoic acid (DOM). While in adult rats, mice, monkeys and humans DOM poorly penetrates the blood-brain barrier, DOM has been shown to be very toxic to fetal in newborn mice, because the blood-brain barrier is incomplete during neurodevelopment. This fact may explain why neonates show a higher sensitivity to neurotoxins like DOM as compared to adult animals. Mechanistic studies on DOM's neurotoxicity have mainly concentrated on the investigation of DOM's effect on neuronal tissue. Recent studies have shown that glia is also involved in DOM's neurotoxicity to the adult as well as the developing nervous system. The scientific literature strongly supports the hypothesis that the microglia may play a critical role in mediating DOM's neurotoxic effects. However, the effect of DOM on microglia has not been systematically investigated. The literature supporting our hypothesis is presented and discussed.
Mayer
A M
AM
Department of Pharmacology, Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, Illinois, USA. amayer@midwestern.edu
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects* / Q000196:embryology / Q000254:growth & development; D007608:Kainic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D008387:Marine Toxins / Q000494:pharmacology*; D051379:Mice; D017628:Microglia / Q000187:drug effects*; D009498:Neurotoxins / Q000494:pharmacology*; D051381:Rats
D008387:Marine Toxins; D009498:Neurotoxins; C012301:domoic acid; D007608:Kainic Acid