Jovangelis González Del Toro ^1,2, Kiara M. Cardona Jordan, M.S.¹, Ruth D. González Bermejo^1,2, and Cristina Velázquez-Marrero*¹

¹Institute of Neurobiology, University of Puerto Rico Medical Sciences Campus, San Juan PR 0092

²University of Puerto Rico, Cayey Campus, Cayey PR 00737

*Principal Investigator and Corresponding Author

INTRODUCTION: Bisphenol-A (BPA), a known endocrine-disrupting agent, is largely used for most polycarbonate plastic-derived products production worldwide. The main sources of BPA exposure for humans include food/drinks consumption alongside airborne particles. Previous research has shown that exposure to BPA levels accepted by the U.S. Environmental Protection Agency (EPA) causes behavioral impairment on spatial learning and memory performance in mice. Prior studies at our lab explored BPA effects on HEK293 cells expressing large potassium calcium- and voltage-dependent channel (BK)-GFP tagged surface distribution in correlation to expression of FKBP5, a known biomarker for anxiety disorders such as PTSD, and β-catenin. Both protein expressions were significantly increased in a dose-dependent manner (2ppm and 20ppm), after BPA exposure well below the accepted EPA levels. Based on this, we hypothesized there would be behavioral impacts associated to development of anxiety disorders like PTSD induced by BPA exposure at said EPA dosages. For this project, our overarching goal was to examine the effects of BPA exposure on contextual fear conditioning and extinction learning.

METHODS: We evaluated in-vivo BPA consumption at 2 and 20ppm concentration for two-weeks of wild-type C57 male mice on contextual fear conditioning and contextual extinction trials (FC/FE), a paradigm used to study anxiety-like behavior.

RESULTS: Data shows increased fear response in conditioning trials and deficits in context extinction learning upon BPA exposure.

CONCLUSIONS: For future experiments, immunohistological analysis of Dorsal Hippocampus (DH) and Basolateral Amygdala (BLA) sampling will be done before and after FC/FE trials to measure expression of β-catenin, FKBP5, and GSK3-beta, a key Wnt-pathway component that plays a role in memory formation and neurogenesis. These results showcasing fear contextual learning deficits could indicate BPA-induced interference on anxiety/fear neural circuits and neuronal intrinsic excitability, denoting further research needed on the implications of this contaminant on learning and anxiety disorders development, along interrelated molecular pathways and biomarkers.

IACUC APPROVAL NUMBER: A830117

AKNOWELEDGEMENTS:

• Dr. Cristina Velázquez, PI: NIH NIAAA 1R01AA027808-01A1, Kiara Cardona, M.S.: The CREST Puerto Rico Center for Environmental Neuroscience (PRCEN).
• The Velazquez Lab Team
• U-RISE – UPR Cayey: NIH T34GM145404