Perinatal Exposure to Aroclor 1254 Exerts a Stimulatory Effect on Parvocellular Pvn Trh mRNA Levels and Has an Inhibitory Action in Response to Salt-Loading Stress

Presentation Number: FRI 126
Date of Presentation: April 1st, 2016

Edith Sánchez-Jaramillo*1, Eduardo Sánchez-Islas1, Gabriela Berenice Gómez-González1, Fidelia Romero2, Victor Rivelino Juárez-González2, Nashiely Yáñez-Recendis1, Roberto Toni3 and Martha Leon-Olea1
1Instituto Nacional de Psiquiatría Ramón de la Fuente, México, Mexico, 2Instituto de Biotecnología UNAM, Cuernavaca, Morelos, Mexico, 3School of Medicine, Bologna, Italy

Abstract

Polychlorinated Biphenyls (PCB) are a class of industrial organohalogen compounds widely present as contaminants in the environment and routinely found in human and animal fat tissues. PCBs are considered as endocrine disruptors and the literature heavily supports its role on different aspects of thyroid hormone (TH) dysregulation. It has been shown that commercial mixtures of PCBs as Aroclor-1254 decreases serum levels of T3, T4, synthesis of associated proteins to TH biosynthesis, activity of deiodinases 1 and 2, TSH b-subunit expression in the pituitary and TRH receptor synthesis in the hypothalamus. As perinatal exposure to Aroclor-1254 alter thyroid function in the developing brain and the exposed animals share some features of primary hypothyroidism in the adulthood, we hypothesized that TRH synthesis could present disturbances in the hypothalamic PVN that control the thyroid axis activity. We also studied the response capacity of PVN TRH neurons to a stressful stimulus. Pregnant Wistar rats received Aroclor 1254, 30 mg/kg BW/day from 10 to 19 gestational day or corn oil (vehicle). Three months later, they were separated in four groups (n=6-8 animals per group): control vehicle (C), control+ salt -loaded (C+SL) (2% NaCl ad libitum in their drinking water per 5 days), Aroclor 1254 (A) and Aroclor 1254 + salt loaded (A+SL). Animals were euthanized after an overdose of anesthesia with pentobarbital (30 mg/kg) and perfused with 4% paraformaldehyde- PBS to analyze TRH mRNA or APV mRNA (as control of SL stimulation) by in situ hybridization.

In utero exposure to Aroclor 1254 produced significant changes in TRH mRNA expression of the PVN. Integrated optical density (IOD) from silver grain exposition to 35S [UTP] TRH cRNA probe [ImageJ (version 1.50D)], increased significantly in perinatal exposed animals to Aroclor 1254 when compared to control [* P <0.05]. Hyperosmotic stimulation produced a significant physiological increase in control rats (** P <0.01) but failure to activate the A+SL group. Analysis of optical density in ranges of 9 categories instead of integrated density units, allowed us to determine punctual changes on lower or higher TRH signal from the PVN [6 ranks for the first 13-100 pixel units and 3 ranges for the last 101-500 pixel units, using -Threshold> Analyse particles> Distribution- ImageJ (version 1.50D)]. Range from 13-20 or 21-28 pixel units increased 2x respect to control rats (***P <0.001) while range from 101-234 pixel units (higher grain number/cumulus) increased 3x in C+SL or in Aroclor 1254 respect to control (***P <0.001). Our results demonstrate that PCBs disrupt the homeostasis of the HPT axis at a central level and also the acute salt-loading stress response.

 

Nothing to Disclose: ES, ES, GBG, FR, VRJ, NY, RT, ML