Evidence map›Paper›PMID 26480925›Full record

ArticleMolecular pharmacology2016

Reduced Myelination and Increased Glia Reactivity Resulting from Severe Neonatal Hyperbilirubinemia.

Andreia Barateiro, Shujuan Chen, Mei-Fei Yueh, Adelaide Fernandes, Helena Sofia Domingues, João Relvas, Olivier Barbier, Nghia Nguyen, Robert H Tukey, Dora Brites

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

Article in Molecular pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
6.9field-weighted citation impact, top 4% 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

24 citing papers in PubMed, 36 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Effect of bilirubin on visuocortical development in preterm infants.Journal of perinatology : official journal of the California Perinatal Association · 2025
    Article
  6. Article
  7. Review
  8. Review
  9. Review
  10. Article
  11. Review
  12. Review
  13. Review
  14. Article
  15. [Role of pyroptosis in bilirubin-induced microglial injury].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2020
    Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. 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

10 authors at 4 institutions in 3 countries.

Andreia BarateiroResearch Institute for Medicines (iMed.UL) (A.B., A.F., D.B.) and Department of Biochemistry and Human Biology (A.F., D.B.), Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal; Laboratory of Environmental Toxicology, Department of Pharmacology, and Chemistry and Biochemistry, University of California San Diego, La Jolla, California (S.C., M-F.Y., N.N., R.H.T.); Departamento de Biologia Experimental, Faculty of Medicine (H.S.D., J.R.) and Instituto de Biologia Molecular e Celular (J.R.), University of Porto, Porto, Portugal; Laboratory of Molecular Pharmacology, CHU de Québec Research Centre and Faculty of Pharmacy, Laval University, Québec, QC, Canada (O.B.).
Shujuan ChenResearch Institute for Medicines (iMed.UL) (A.B., A.F., D.B.) and Department of Biochemistry and Human Biology (A.F., D.B.), Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal; Laboratory of Environmental Toxicology, Department of Pharmacology, and Chemistry and Biochemistry, University of California San Diego, La Jolla, California (S.C., M-F.Y., N.N., R.H.T.); Departamento de Biologia Experimental, Faculty of Medicine (H.S.D., J.R.) and Instituto de Biologia Molecular e Celular (J.R.), University of Porto, Porto, Portugal; Laboratory of Molecular Pharmacology, CHU de Québec Research Centre and Faculty of Pharmacy, Laval University, Québec, QC, Canada (O.B.).
Mei-Fei YuehResearch Institute for Medicines (iMed.UL) (A.B., A.F., D.B.) and Department of Biochemistry and Human Biology (A.F., D.B.), Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal; Laboratory of Environmental Toxicology, Department of Pharmacology, and Chemistry and Biochemistry, University of California San Diego, La Jolla, California (S.C., M-F.Y., N.N., R.H.T.); Departamento de Biologia Experimental, Faculty of Medicine (H.S.D., J.R.) and Instituto de Biologia Molecular e Celular (J.R.), University of Porto, Porto, Portugal; Laboratory of Molecular Pharmacology, CHU de Québec Research Centre and Faculty of Pharmacy, Laval University, Québec, QC, Canada (O.B.).
Adelaide FernandesResearch Institute for Medicines (iMed.UL) (A.B., A.F., D.B.) and Department of Biochemistry and Human Biology (A.F., D.B.), Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal; Laboratory of Environmental Toxicology, Department of Pharmacology, and Chemistry and Biochemistry, University of California San Diego, La Jolla, California (S.C., M-F.Y., N.N., R.H.T.); Departamento de Biologia Experimental, Faculty of Medicine (H.S.D., J.R.) and Instituto de Biologia Molecular e Celular (J.R.), University of Porto, Porto, Portugal; Laboratory of Molecular Pharmacology, CHU de Québec Research Centre and Faculty of Pharmacy, Laval University, Québec, QC, Canada (O.B.).
Helena Sofia DominguesResearch Institute for Medicines (iMed.UL) (A.B., A.F., D.B.) and Department of Biochemistry and Human Biology (A.F., D.B.), Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal; Laboratory of Environmental Toxicology, Department of Pharmacology, and Chemistry and Biochemistry, University of California San Diego, La Jolla, California (S.C., M-F.Y., N.N., R.H.T.); Departamento de Biologia Experimental, Faculty of Medicine (H.S.D., J.R.) and Instituto de Biologia Molecular e Celular (J.R.), University of Porto, Porto, Portugal; Laboratory of Molecular Pharmacology, CHU de Québec Research Centre and Faculty of Pharmacy, Laval University, Québec, QC, Canada (O.B.).
João RelvasResearch Institute for Medicines (iMed.UL) (A.B., A.F., D.B.) and Department of Biochemistry and Human Biology (A.F., D.B.), Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal; Laboratory of Environmental Toxicology, Department of Pharmacology, and Chemistry and Biochemistry, University of California San Diego, La Jolla, California (S.C., M-F.Y., N.N., R.H.T.); Departamento de Biologia Experimental, Faculty of Medicine (H.S.D., J.R.) and Instituto de Biologia Molecular e Celular (J.R.), University of Porto, Porto, Portugal; Laboratory of Molecular Pharmacology, CHU de Québec Research Centre and Faculty of Pharmacy, Laval University, Québec, QC, Canada (O.B.).
Olivier BarbierResearch Institute for Medicines (iMed.UL) (A.B., A.F., D.B.) and Department of Biochemistry and Human Biology (A.F., D.B.), Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal; Laboratory of Environmental Toxicology, Department of Pharmacology, and Chemistry and Biochemistry, University of California San Diego, La Jolla, California (S.C., M-F.Y., N.N., R.H.T.); Departamento de Biologia Experimental, Faculty of Medicine (H.S.D., J.R.) and Instituto de Biologia Molecular e Celular (J.R.), University of Porto, Porto, Portugal; Laboratory of Molecular Pharmacology, CHU de Québec Research Centre and Faculty of Pharmacy, Laval University, Québec, QC, Canada (O.B.).
Nghia NguyenResearch Institute for Medicines (iMed.UL) (A.B., A.F., D.B.) and Department of Biochemistry and Human Biology (A.F., D.B.), Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal; Laboratory of Environmental Toxicology, Department of Pharmacology, and Chemistry and Biochemistry, University of California San Diego, La Jolla, California (S.C., M-F.Y., N.N., R.H.T.); Departamento de Biologia Experimental, Faculty of Medicine (H.S.D., J.R.) and Instituto de Biologia Molecular e Celular (J.R.), University of Porto, Porto, Portugal; Laboratory of Molecular Pharmacology, CHU de Québec Research Centre and Faculty of Pharmacy, Laval University, Québec, QC, Canada (O.B.).
Robert H TukeyResearch Institute for Medicines (iMed.UL) (A.B., A.F., D.B.) and Department of Biochemistry and Human Biology (A.F., D.B.), Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal; Laboratory of Environmental Toxicology, Department of Pharmacology, and Chemistry and Biochemistry, University of California San Diego, La Jolla, California (S.C., M-F.Y., N.N., R.H.T.); Departamento de Biologia Experimental, Faculty of Medicine (H.S.D., J.R.) and Instituto de Biologia Molecular e Celular (J.R.), University of Porto, Porto, Portugal; Laboratory of Molecular Pharmacology, CHU de Québec Research Centre and Faculty of Pharmacy, Laval University, Québec, QC, Canada (O.B.) s18chen@ucsd.edu dbrites@ff.ulisboa.pt.
Dora BritesResearch Institute for Medicines (iMed.UL) (A.B., A.F., D.B.) and Department of Biochemistry and Human Biology (A.F., D.B.), Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal; Laboratory of Environmental Toxicology, Department of Pharmacology, and Chemistry and Biochemistry, University of California San Diego, La Jolla, California (S.C., M-F.Y., N.N., R.H.T.); Departamento de Biologia Experimental, Faculty of Medicine (H.S.D., J.R.) and Instituto de Biologia Molecular e Celular (J.R.), University of Porto, Porto, Portugal; Laboratory of Molecular Pharmacology, CHU de Québec Research Centre and Faculty of Pharmacy, Laval University, Québec, QC, Canada (O.B.) s18chen@ucsd.edu dbrites@ff.ulisboa.pt.
Universidade do Porto · PTUniversity of Lisbon · PTUniversité Laval · CAUniversity of California, San Diego · US

Funding

Yeast Genetics and Stress Response Genes-BiomedicalP42ES010337 · NIEHS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TUKEY, ROBERT H · 2000 to 2022
$69.8M
Xenobiotic sensors PXR and CAR and regulation of the UGT1 locusR01GM086713 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TUKEY, ROBERT H · 2009 to 2017
$2.6M
Neonatal hyperbilirubinemia in a humanized UGT1 animal modelR01GM100481 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TUKEY, ROBERT H · 2012 to 2015
$1.3M
Organ-specific Ugt1 profiling in detoxifying the anticancer drug CPT-11R21CA171008 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHEN, SHUJUAN · 2012 to 2013
$361k
NCI NIH HHS R21 CA171008NCI NIH HHS R21CA171008NIEHS NIH HHS ES010337NIEHS NIH HHS P42 ES010337NIGMS NIH HHS GM086713NIGMS NIH HHS GM100481NIGMS NIH HHS R01 GM086713NIGMS NIH HHS R01 GM100481
6 · The paper itself

Abstract

Bilirubin-induced neurologic dysfunction (BIND) and kernicterus has been used to describe moderate to severe neurologic dysfunction observed in children exposed to excessive levels of total serum bilirubin (TSB) during the neonatal period. Here we use a new mouse model that targets deletion of the Ugt1 locus and the Ugt1a1 gene in liver to promote hyperbilirubinemia-induced seizures and central nervous system toxicity. The accumulation of TSB in these mice leads to diffuse yellow coloration of brain tissue and a marked cerebellar hypoplasia that we characterize as kernicterus. Histologic studies of brain tissue demonstrate that the onset of severe neonatal hyperbilirubinemia, characterized by seizures, leads to alterations in myelination and glia reactivity. Kernicterus presents as axonopathy with myelination deficits at different brain regions, including pons, medulla oblongata, and cerebellum. The excessive accumulation of TSB in the early neonatal period (5 days after birth) promotes activation of the myelin basic protein (Mbp) gene with an accelerated loss of MBP that correlates with a lack of myelin sheath formation. These changes were accompanied by increased astroglial and microglial reactivity, possibly as a response to myelination injury. Interestingly, cerebellum was the area most affected, with greater myelination impairment and glia burden, and showing a marked loss of Purkinje cells and reduced arborization of the remaining ones. Thus, kernicterus in this model displays not only axonal damage but also myelination deficits and glial activation in different brain regions that are usually related to the neurologic sequelae observed after severe hyperbilirubinemia.

Indexed as

Severity of Illness IndexAnimalsHumansHyperbilirubinemia, NeonatalMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicMonosaccharide Transport ProteinsMyelin SheathNeurogliaUDP-Galactose TranslocatorsMonosaccharide Transport ProteinsUDP-Galactose Translocators

Identifiers

PMID26480925
PMCPMC4702100
OpenAlexW1794816422

What OpenQuestion holds

Textmetadata
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.