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

2019· article· en· W3167114586 on OpenAlexaff
Warren W. Burggren, Naim M. Bautista, Trevor J. Hamilton, Dao H. Ho

Bibliographic record

VenueThe FASEB Journal · 2019
Typearticle
Languageen
FieldEnvironmental Science
TopicEnvironmental Toxicology and Ecotoxicology
Canadian institutionsMacEwan University
FundersGulf of Mexico Research InitiativeU.S. Department of Defense
KeywordsZebrafishIn vivoBlood–brain barrierBiologyCrude oilIn vitroAnimal behaviorNeuroscienceFish <Actinopterygii>Cell biologyPhysiologyZoologyGeneCentral nervous systemBiochemistryGenetics

Abstract

fetched live from OpenAlex

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 Information Gulf of Mexico Research Initiative U.S. Army/Department of Defense This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.001
Scholarly communication0.0010.001
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.016
GPT teacher head0.245
Teacher spread0.229 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations1
Published2019
Admission routes1
Has abstractyes

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