Next Article in Journal / Special Issue
Azaspiracid Shellfish Poisoning: A Review on the Chemistry, Ecology, and Toxicology with an Emphasis on Human Health Impacts
Previous Article in Journal
Actinomycetes from Sediments in the Trondheim Fjord, Norway: Diversity and Biological Activity
Previous Article in Special Issue
Evaluation of Harmful Algal Bloom Outreach Activities
Open AccessArticle

Regional Susceptibility to Domoic Acid in Primary Astrocyte Cells Cultured from the Brain Stem and Hippocampus

Toxicology Research Division, Food Directorate, Health Products and Foods Branch, Banting, Malaysia
Department of Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Enghelab, Tehran, Iran
Author to whom correspondence should be addressed.
Mar. Drugs 2008, 6(1), 25-38;
Received: 28 November 2007 / Revised: 23 January 2008 / Accepted: 9 February 2008 / Published: 14 February 2008
(This article belongs to the Special Issue Marine Toxins)
Domoic acid is a marine biotoxin associated with harmful algal blooms and is the causative agent of amnesic shellfish poisoning in marine animals and humans. It is also an excitatory amino acid analog to glutamate and kainic acid which acts through glutamate receptors eliciting a very rapid and potent neurotoxic response. The hippocampus, among other brain regions, has been identified as a specific target site having high sensitivity to DOM toxicity. Histopathology evidence indicates that in addition to neurons, the astrocytes were also injured. Electron microscopy data reported in this study further supports the light microscopy findings. Furthermore, the effect of DOM was confirmed by culturing primary astrocytes from the hippocampus and the brain stem and subsequently exposing them to domoic acid. The RNA was extracted and used for biomarker analysis. The biomarker analysis was done for the early response genes including c-fos, c-jun, c-myc, Hsp-72; specific marker for the astrocytes- GFAP and the glutamate receptors including GluR 2, NMDAR 1, NMDAR 2A and B. Although, the astrocyte-GFAP and c-fos were not affected, c-jun and GluR 2 were down-regulated. The microarray analysis revealed that the chemokines / cytokines, tyrosine kinases (Trk), and apoptotic genes were altered. The chemokines that were up-regulated included - IL1-a, IL-1B, IL-6, the small inducible cytokine, interferon protein IP-10, CXC chemokine LIX, and IGF binding proteins. The Bax, Bcl-2, Trk A and Trk B were all downregulated. Interestingly, only the hippocampal astrocytes were affected. Our findings suggest that astrocytes may present a possible target for pharmacological interventions for the prevention and treatment of amnesic shellfish poisoning and for other brain pathologies involving excitotoxicity View Full-Text
Keywords: Domoic acid; astrocytes; susceptibility; semi-quantitative analysis; electron microscopy Domoic acid; astrocytes; susceptibility; semi-quantitative analysis; electron microscopy
Show Figures

Figure 1

MDPI and ACS Style

Gill, S.S.; Hou, Y.; Ghane, T.; Pulido, O.M. Regional Susceptibility to Domoic Acid in Primary Astrocyte Cells Cultured from the Brain Stem and Hippocampus. Mar. Drugs 2008, 6, 25-38.

Show more citation formats Show less citations formats

Article Access Map by Country/Region

Only visits after 24 November 2015 are recorded.
Back to TopTop