Evidence map›Paper›PMID 29091768›Full record

ArticleCell reports2017

Evolutionarily Conserved Roles for Blood-Brain Barrier Xenobiotic Transporters in Endogenous Steroid Partitioning and Behavior.

Samantha J Hindle, Roeben N Munji, Elena Dolghih, Garrett Gaskins, Souvinh Orng, Hiroshi Ishimoto, Allison Soung, Michael DeSalvo, Toshihiro Kitamoto, Michael J Keiser and 3 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
3.2field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

37 citing papers in PubMed, 73 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Review
  8. Understanding the Blood-Brain Barrier: From Physiology to Pathology.Advances in experimental medicine and biology · 2025
    Review
  9. Role ofFrontiers in pharmacology · 2025
    Review
  10. Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Glial Tiling in the Insect Nervous System.Frontiers in cellular neuroscience · 2022
    Review
  18. Review
  19. Form and Function of the Vertebrate and Invertebrate Blood-Brain Barriers.International journal of molecular sciences · 2021
    Review
  20. Drosophila ßNature communications · 2021
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 5 institutions in 2 countries.

Samantha J HindleDepartment of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, CA, USA.
Roeben N MunjiDepartment of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, CA, USA; Division of Clinical Pharmacology and Experimental Therapeutics, University of California San Francisco, San Francisco, CA, USA; Department of Anatomy, University of California San Francisco, San Francisco, CA, USA; Department of Pharmacology, University of California San Diego, La Jolla, CA, USA.
Elena DolghihDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, USA.
Garrett GaskinsDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, USA; Institute for Neurodegenerative Disease, University of California San Francisco, San Francisco, CA, USA; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA.
Souvinh OrngDepartment of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, CA, USA.
Hiroshi IshimotoDivision of Biological Science, Graduate School of Science, Nagoya University, Japan.
Allison SoungDepartment of Anatomy, University of California San Francisco, San Francisco, CA, USA; Department of Pharmacology, University of California San Diego, La Jolla, CA, USA.
Michael DeSalvoDepartment of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, CA, USA.
Toshihiro KitamotoDepartment of Anesthesia, University of Iowa, Iowa City, Iowa, USA.
Michael J KeiserDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, USA; Institute for Neurodegenerative Disease, University of California San Francisco, San Francisco, CA, USA; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA.
Matthew P JacobsonDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, USA.
Richard DanemanDepartment of Anatomy, University of California San Francisco, San Francisco, CA, USA; Department of Pharmacology, University of California San Diego, La Jolla, CA, USA. Electronic address: rdaneman@ucsd.edu.
Roland J BaintonDepartment of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, CA, USA. Electronic address: roland.bainton@ucsf.edu.
University of California, San Francisco · USUniversity of California, San Diego · USInstitute for Neurodegenerative Disorders · USNagoya University · JPUniversity of Iowa · US

Funding

Structure, States and Transition in ABC Transporters pp360-431P01GM111126 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SALI, ANDREJ · 2015 to 2019
$9.8M
CLINICAL, PHARMACOLOGY, DRUG ACTION &PHARMACOKINETICST32GM007546 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Radojka Savic · 1985 to 2026
$8.9M
BMI Bioinformatics Training GrantsT32GM067547 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HERNANDEZ, RYAN D. · 2003 to 2022
$6.6M
Comprehensive Anesthesia Research TrainingT32GM008440 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Judith Hellman · 1996 to 2026
$5.5M
Regulation of blood-brain barrier formation and function by EHDsR01NS091281 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DANEMAN, RICHARD · 2015 to 2019
$1.9M
Physiology and regulation of drug transport across the blood brain barrierR01GM081863 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BAINTON, ROLAND J · 2007 to 2011
$1.4M
A platform to predict side-effect targets for drugsR44GM093456 · NIGMS · SEACHANGE PHARMACEUTICALS, INC. · PI HODGE, CARL NICHOLAS, KEISER, MICHAEL JAMES · 2013 to 2014
$910k
Discovering fundamental metabolic control processes of the blood brain barrierR21NS082856 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BAINTON, ROLAND J · 2013 to 2014
$430k
A platform for rapid characterization of metabolic disrupters in whole animalsR21ES021412 · NIEHS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ASHRAFI, KAVEH, BAINTON, ROLAND J · 2012 to 2013
$420k
Drug Repurposing using Pharmacological NetworksR43GM093456 · NIGMS · SEACHANGE PHARMACEUTICALS, INC. · PI KEISER, MICHAEL JAMES · 2010 to 2010
$203k
NIEHS NIH HHS R21 ES021412NIGMS NIH HHS P01 GM111126NIGMS NIH HHS R01 GM081863NIGMS NIH HHS R43 GM093456NIGMS NIH HHS R44 GM093456NIGMS NIH HHS T32 GM007546NIGMS NIH HHS T32 GM008440NIGMS NIH HHS T32 GM067547NINDS NIH HHS R01 NS091281NINDS NIH HHS R21 NS082856
6 · The paper itself

Abstract

Central nervous system (CNS) chemical protection depends upon discrete control of small-molecule access by the blood-brain barrier (BBB). Curiously, some drugs cause CNS side-effects despite negligible transit past the BBB. To investigate this phenomenon, we asked whether the highly BBB-enriched drug efflux transporter MDR1 has dual functions in controlling drug and endogenous molecule CNS homeostasis. If this is true, then brain-impermeable drugs could induce behavioral changes by affecting brain levels of endogenous molecules. Using computational, genetic, and pharmacologic approaches across diverse organisms, we demonstrate that BBB-localized efflux transporters are critical for regulating brain levels of endogenous steroids and steroid-regulated behaviors (sleep in Drosophila and anxiety in mice). Furthermore, we show that MDR1-interacting drugs are associated with anxiety-related behaviors in humans. We propose a general mechanism for common behavioral side effects of prescription drugs: pharmacologically challenging BBB efflux transporters disrupts brain levels of endogenous substrates and implicates the BBB in behavioral regulation.

Indexed as

AldosteroneAnimalsATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily B, Member 1Behavior, AnimalBinding SitesBiological EvolutionBlood-Brain BarrierBrainCentral Nervous SystemCyclosporineDatabases, ChemicalDrosophilaDrosophila ProteinsEcdysteroneGonadal Steroid HormonesAldosteroneATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily B, Member 1CyclosporineDrosophila ProteinsEcdysteroneGonadal Steroid Hormonesmdr65 protein, DrosophilaXenobioticsbehaviorblood brain barriercentral nervous systemdrug side effect mechanismsdrug transportersendobioticssteroid hormonestoxicology

Identifiers

PMID29091768
PMCPMC5774027
OpenAlexW2611618612

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.