Blood‐Brain Barrier as a Novel Link between Crude Oil Exposure and Behavioral Dysfunctions?

Abstract

Low levels of exposure to crude oil and/or its derivatives are associated with numerous changes in coping responses from molecular to organismal levels in vertebrates ranging from fishes to humans. Less understood are behavioral implications of exposure, with a handful of studies suggesting that crude oil leads to behavior that is “riskier” and more aggressive. Moreover, the mechanisms underlying such behavioral changes are largely unknown. Given that blood‐brain barrier (BBB) disruption is implicated in many behavioral abnormalities, a likely, although uninvestigated, link between crude oil and associated behavioral changes is blood‐brain barrier dysfunction. We hypothesize that alterations in the integrity of the BBB is correlated with oil‐induced behavioral changes. In this poster we describe our programmatic approach consisting of three phases to test this hypothesis. Our strategy, based on three experimental approaches, tests the effects of crude oil exposure in the form of High Energy Water Accommodated Fractions (HEWAFs). 1) We have quantified behavioral changes in animal models (zebrafish, betta fish, and mouse). 2) We have assessed BBB integrity by recording real‐time transendothelial electrical resistance (TEER) of in vitro “BBBs” formed by a confluent layer of brain microvascular endothelial cells (BMECs), and assessed gene expression in these cultured endothelial cells. 3) We will correlate in vivo with in vitro findings. In the first phase of our study, initial in vivo assessment using both Siamese fighting fish and zebrafish as models, indicates that fish exposed to very low levels of crude oil HEWAF show significantly increased aggressive behavior, and reduced reproductive and other behaviors, without otherwise showing morphological or growth effects. The second phase involved high‐throughput in vitro assessment using mouse BMECs as a simplified model of the BBB. These experiments indicated that acute exposure to crude oil extracts, as well as environmentally relevant concentrations ofbenzo(a)pyrene (one of the components of crude oil), resulted in significant decreases in TEER within the first 3 to 6 h of exposure. These barrier changes were accompanied by changes in expression of tight junction‐associated proteins such as significantly reduced expression in BMECs of the cell adhesion protein Cldn5, 48h after exposure to 8% HEWAF. Expression of Tjp1, a scaffolding protein that links tight junction (TJ) transmembrane proteins, was also decreased after exposure to just 2% HEWAF. The third, future phase will correlate in vivo with in vitro findings by first inducing behavioral dysfunction in animal models using crude oil HEWAF exposure, and then isolating and culturing BMECs of these animals to determine if in vivo exposure results in the same persistent changes in BBB leakiness and reduced BBB viability that was observed in the phase two in vitro studies. By applying our multi‐faceted experimental approach, we will be able to more fully elucidate the impact of crude oil on the blood‐brain barrier, and discover how this can, in turn, affect behavior in animals and man.Support or Funding InformationGulf of Mexico Research Initiative U.S. Army/Department of DefenseThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.