Histopathological and molecular changes produced by hippocampal microinjection of domoic acid

Shenfeng Qiu, Margarita C. Currás-Collazo

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The phytoplankton-derived neurotoxin, domoic acid (DOM), frequently causes poisoning of marine animals and poses an increasing threat to public health through contamination of seafood. In this study, we used stereotactic microinjection technique to administer varying amounts of DOM into the hippocampal CA1 region in order to examine potential histopathological changes after injection of sub-lethal concentrations to CA1 pyramidal neurons. Gross anatomical abnormalities in CA1 were observed at above 10 μM DOM (3 pmol in 0.3 μl saline). At 1 mM concentration, DOM produces both ipsilateral and contralateral neuronal cell death in CA1, CA3 as well as dentate gyrus subfields. Animal behavioral changes after microinjection were similar to those observed by previous studies through systemic DOM injection. Neuronal degeneration was paralleled by reduced glutamate receptor (NR1, GluR1 and GluR6/7) immunolabeling throughout the whole hippocampal formation. Pre-injection of the AMPA/KA receptor antagonist NBQX (10 μM, 0.3 μl) blocked 1 mM DOM-induced neuronal degeneration as well as behavioral symptoms. At concentrations lower than 10 μM, no histopathological changes were observed microscopically, nor were the levels of immunostaining of NR1, GluR1, GluR6/7 different. However, increased immunolabeling of autophosphorylated calcium-calmodulin-dependent kinase II (CaMKII, p-Thr286) and phosphorylated cAMP response element binding protein (CREB, p-Ser133) were observed at 24 h post-injection, suggesting that altered intracellular signal transduction mediated by GluRs might be an adaptive cellular protective mechanism against DOM-induced neurotoxicity.

Original languageEnglish (US)
Pages (from-to)354-362
Number of pages9
JournalNeurotoxicology and Teratology
Volume28
Issue number3
DOIs
StatePublished - May 2006
Externally publishedYes

Fingerprint

Microinjections
Injections
Animals
Stereotaxic Techniques
Capital Punishment
Hippocampal CA1 Region
Phytoplankton
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Cyclic AMP Response Element-Binding Protein
Seafood
Behavioral Symptoms
Signal transduction
Calcium-Calmodulin-Dependent Protein Kinases
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
AMPA Receptors
Pyramidal Cells
Dentate Gyrus
Neurotoxins
Glutamate Receptors
Public health

Keywords

  • Calcium-calmodulin-dependent kinase II
  • cAMP response element binding protein
  • Glutamate receptors
  • Hippocampus
  • Immunohistopathology
  • Marine toxins

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Neuroscience(all)
  • Toxicology

Cite this

Histopathological and molecular changes produced by hippocampal microinjection of domoic acid. / Qiu, Shenfeng; Currás-Collazo, Margarita C.

In: Neurotoxicology and Teratology, Vol. 28, No. 3, 05.2006, p. 354-362.

Research output: Contribution to journalArticle

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