title: Neurohistochemical biomarkers of the marine neurotoxicant, domoic acid.
abstract: Domoic acid and its potent excitotoxic analogues glutamic acid and kainic acid, are synthesized by marine algae such as seaweed and phytoplankton. During an algal bloom, domoic acid may enter the food web through its consumption by a variety of marine organisms held in high regard as seafoods by both animals and humans. These seafoods include clams, mussels, oysters, anchovies, sardines, crabs, and scallops, among others. Animals, such as pelicans, cormorants, loons, grebes, sea otters, dolphins, and sea lions, which consume seafood contaminated with domoic acid, suffer disorientation and often death. Humans consuming contaminated seafood may suffer seizures, amnesia and also sometimes death. In addition to analytical measurement of domoic acid exposure levels in algae and/or seafood, it is useful to be able to identify the mode of toxicity through post-mortem evaluation of the intoxicated animal. In the present study, using the rat as an animal model of domoic acid intoxication, we compared histochemical staining of the limbic system and especially the hippocampus with degeneration-selective techniques (Fluoro-Jade and silver), a conventional Nissl stain for cytoplasm (Cresyl violet), a myelin-selective stain (Black-Gold), an astrocyte-specific stain (glial fibrillary acidic protein), early/immediate gene responses (c-Fos and c-Jun), as well as for heat shock protein (HSP-72) and blood-brain barrier integrity (rat IgG). The results demonstrate that the degeneration-selective stains are the biomarkers of domoic acid neurotoxicity that are the most useful and easy to discern when screening brain sections at low magnification. We also observed that an impairment of blood-brain barrier integrity within the piriform cortex accompanied the onset of domoic acid neurotoxicity.
authors.affiliation: Division of Neurotoxicology, National Center for Toxicological Research/FDA 3900 NCTR Drive, Jefferson, Arkansas 72079, USA. AScallet@nctr.fda.gov
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Scallet
authors.forename: Larry C
authors.initials: LC
authors.lastname: Schmued
authors.forename: Jan N
authors.initials: JN
authors.lastname: Johannessen
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier; D004396:Coloring Agents; D018891:Dentate Gyrus / Q000473:pathology; D005452:Fluoresceins; D005456:Fluorescent Dyes; D017781:Genes, Immediate-Early; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D007608:Kainic Acid / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000633:toxicity; D008297:Male; D009186:Myelin Sheath / Q000378:metabolism; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000473:pathology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009498:Neurotoxins / Q000633:toxicity*; D009930:Organic Chemicals; D010710:Phosphates; D051381:Rats; D017207:Rats, Sprague-Dawley; D016622:Silver Staining
chemical_list: C121848:Black-Gold; D004396:Coloring Agents; D005452:Fluoresceins; D005456:Fluorescent Dyes; D005904:Glial Fibrillary Acidic Protein; D006360:Heat-Shock Proteins; D009498:Neurotoxins; D009930:Organic Chemicals; D010710:Phosphates; C435731:fluoro jade; C012301:domoic acid; D007608:Kainic Acid