NDLI: Malformation of certain brain blood vessels caused by TCDD activation of Ahr2/Arnt1 signaling in developing zebrafish.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Teraoka, Hiroki Ogawa, Akira Kubota, Akira Stegeman, John J. Peterson, Richard E. Hiraga, Takeo
Description	Country affiliation: Japan Author Affiliation: Teraoka H ( School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu 069-8501, Japan. hteraoka@rakuno.ac.jp)
Abstract	2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) causes various signs of toxicity in early life stages of vertebrates through activation of the aryl hydrocarbon receptor (AHR). The AHR also plays important roles in normal development in mice, and AHR(-/-) mice show abnormal development of vascular structures in various blood vessels. Our previous studies revealed that Ahr type 2 (Ahr2) activation by TCDD and beta-naphthoflavone (BNF) caused a significant decrease in blood flow in the dorsal midbrain of zebrafish embryos. Here we report effects of TCDD exposure on the morphology of some blood vessels in the head of developing zebrafish. TCDD caused concentration-dependent anatomical rearrangements in the shape of the prosencephalic artery in zebrafish larvae. In contrast, no major vascular defects were recognized in the trunk and tail regions following exposure to TCDD at least at the concentrations used. Essentially, the same observations were also confirmed in BNF-exposed larvae. Knock-down of either Ahr2 or Ahr nuclear translocator type 1 (Arnt1) by morpholino oligonucleotides (MOs) protected larvae against abnormal shape of the prosencephalic artery caused by TCDD and BNF. On the other hand, knock-down of Ahr2 or Arnt1 in vehicle-exposed zebrafish larvae had no clear effect on morphology of the prosencephalic artery or trunk vessels. Ascorbic acid, an antioxidant, protected against the TCDD-induced decrease in blood flow through the prosencephalic artery, but not the abnormal morphological changes in the shape of this artery. These results indicate that activation of Ahr2/Arnt1 pathway by TCDD and BNF affects the shape of certain blood vessels in the brain of developing zebrafish.
File Format	HTM / HTML
ISSN	0166445X
e-ISSN	18791514
DOI	10.1016/j.aquatox.2010.05.003
Journal	Aquatic Toxicology
Issue Number	2
Volume Number	99
Language	English
Publisher	Elsevier
Publisher Date	2010-08-15
Publisher Place	Netherlands
Access Restriction	Open
Subject Keyword	Discipline Toxicology Blood Vessels Drug Effects Toxicity Signal Transduction Water Pollutants, Chemical Zebrafish Physiology Animals Antioxidants Pharmacology Ascorbic Acid Gene Knockdown Techniques Head Blood Supply Larva Receptors, Aryl Hydrocarbon Metabolism Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Health, Toxicology and Mutagenesis Aquatic Science

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