Blood‐Brain Barrier as a Novel Link between Crude Oil Exposure and Behavioral Dysfunctions?
Notice bibliographique
Résumé
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 .
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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».