Benzyl Butyl Phthalate (BBP) Treatment Induces Social Deficits, Decreases Fear Conditioning and Alters Amygdalar MeCP2 in Rats

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 338-354-Physiological Impacts of Endocrine Disrupting Chemicals
Basic/Translational
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-354
Adrienne Betz*, Danielle DeBartolo, Sahani Jayatilaka and Jugal Joshi
Quinnipiac University, Hamden
Benzyl Butyl Phthalate (BBP) is an industrial plasticizer that has an unknown action in the central nervous system. Phthalates have recently been associated with behavioral actions that are linked to their endocrine disrupting properties. The purpose of this study was to investigate the behavioral and molecular effects of neonatal and adolescent exposure to BBP. In the first set of experiments we administered BBP (2.5 and 10.0 μg/ml) in food pellets to pregnant rats until post natal day 23 until pups were weaned. We found increased serum levels of 17β-Estradiol in male offspring suggesting BBP can invoke changes in the endocrine system. Anogenital distance (AGD) is commonly regarded as a hormonally sensitive developmental measure in rodents. We found AGD and the cube root of body weight was decreased in male offspring indicating BBP decreases masculinization. In this study we also found alterations in body weight in both male and female offspring of BBP-treated female dams. This is consistent with other studies administering EDCs to rodents. There was a significant decrease in brain weights suggesting processes regulating brain development and function such as synaptic plasticity, neuronal growth and organizing the neural circuit are influenced by the deleterious effects phthalate exposure.  Lastly, animals showed increased aberrant social behavior and no gross motor changes. In the second study, we chronically administered BBP in the drinking water (5.0 ppm and 10.0 ppm) throughout adolescence and into the adult phase of life. Their behavior was then assessed in tests of fear conditioning and sociability. BBP treated rats showed decreased freezing in fear conditioning, and increased aberrant social behavior. Additionally, we found BBP decreased amygdalar MeCP2 and ERK 1/2 levels that correlated with tests of sociability, but no changes in stress related proteins such as NFkB. We also found alterations in endocrine responses as measured by body weight without changes in food consumption suggesting disruption of metabolism and body homeostasis. We suggest that BBP administration disrupts normal learning and social behavior, and that these effects could be related to alterations of amygdala function. Ongoing work includes analysis of amygdalar estrogen receptor ratios (alpha and beta), CREB and UBE3a protein levels. Additionally, we are assessing neuronal maturation and development with spine density investigations in the hippocampus and amygdala. These findings indicate a compelling need for evaluation of acceptable levels of exposure to phthalates present in the environment.

Nothing to Disclose: AB, DD, SJ, JJ

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: Quinnipiac University
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