Transcriptional profiling of rat hypothalamus response to 2,3,7,8-tetrachlorodibenzo-p-dioxin

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Houlahan , K E , Prokopec , S D , Moffat , I D , Lindén , J , Lensu , S , Okey , A B , Pohjanvirta , R & Boutros , P C 2015 , ' Transcriptional profiling of rat hypothalamus response to 2,3,7,8-tetrachlorodibenzo- p -dioxin ' , Toxicology , vol. 328 , pp. 93-101 . https://doi.org/10.1016/j.tox.2014.12.016

Title: Transcriptional profiling of rat hypothalamus response to 2,3,7,8-tetrachlorodibenzo-p-dioxin
Author: Houlahan, Kathleen E.; Prokopec, Stephenie D.; Moffat, Ivy D.; Lindén, Jere; Lensu, Sanna; Okey, Allan B.; Pohjanvirta, Raimo; Boutros, Paul C.
Contributor: University of Helsinki, Finnish Food Safety Authority (EVIRA)
University of Helsinki, Departments of Faculty of Veterinary Medicine
Date: 2015-02
Language: eng
Number of pages: 9
Belongs to series: Toxicology
ISSN: 0300-483X
URI: http://hdl.handle.net/10138/203733
Abstract: In some mammals, halogenated aromatic hydrocarbon (HAH) exposure causes wasting syndrome, defined as significant weight loss associated with lethal outcomes. The most potent HAH in causing wasting is 2,3,7,8-tetrachlorodibenzo-rho-dioxin (TCDD), which exerts its toxic effects through the aryl hydrocarbon receptor (AHR). Since TCDD toxicity is thought to predominantly arise from dysregulation of AHR-transcribed genes, it was hypothesized that wasting syndrome is a result of to TCDD-induced dysregulation of genes involved in regulation of food-intake. As the hypothalamus is the central nervous systems' regulatory center for food-intake and energy balance. Therefore, mRNA abundances in hypothalamic tissue from two rat strains with widely differing sensitivities to TCDD-induced wasting syndrome: TCDD-sensitive Long-Evans rats and TCDD-resistant Han/Wistar rats, 23 h after exposure to TCDD (100 mu g/kg) or corn oil vehicle. TCDD exposure caused minimal transcriptional dysregulation in the hypothalamus, with only 6 genes significantly altered in Long-Evans rats and 15 genes in Han/Wistar rats. Two of the most dysregulated genes were Cyp1a1 and Nqo1, which are induced by TCDD across a wide range of tissues and are considered sensitive markers of TCDD exposure. The minimal response of the hypothalamic transcriptome to a lethal dose of TCDD at an early time-point suggests that the hypothalamus is not the predominant site of initial events leading to hypophagia and associated wasting. TCDD may affect feeding behaviour via events upstream or downstream of the hypothalamus, and further work is required to evaluate this at the level of individual hypothalamic nuclei and subregions. (C) 2014 The Authors. Published by Elsevier Ireland Ltd.
Subject: AHR
TCDD
Microarray
Hypothalamus
Feed restriction
ARYL-HYDROCARBON RECEPTOR
MESSENGER-RNA EXPRESSION
TISSUE GROWTH-FACTOR
AH GENE BATTERY
RESISTANT RAT
WASTING SYNDROME
INDUCED ANOREXIA
ENERGY-BALANCE
PROBE LEVEL
FOOD-INTAKE
413 Veterinary science
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