ArticlePloS one2011
Modulation of Mrp1 (ABCc1) and Pgp (ABCb1) by bilirubin at the blood-CSF and blood-brain barriers in the Gunn rat.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 61 citations in OpenAlex.
- Hyperbilirubinemia and phototherapy differentially alter hippocampal transcriptome in the preterm Gunn rat model.Pediatric research · 2026Article
- Mechanistic insights into the liver-brain axis during chronic liver disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- Bilirubin and Redox Stress in Age-Related Brain Diseases.Antioxidants (Basel, Switzerland) · 2023Review
- Article
- Models of bilirubin neurological damage: lessons learned and new challenges.Pediatric research · 2023Review
- ATP-binding cassette (ABC) drug transporters in the developing blood-brain barrier: role in fetal brain protection.Cellular and molecular life sciences : CMLS · 2022Review
- Bile Duct Ligation Impairs Function and Expression of Mrp1 at Rat Blood-Retinal Barrier via Bilirubin-Induced P38 MAPK Pathway Activations.International journal of molecular sciences · 2022Article
- Vascular network expansion, integrity of blood-brain interfaces, and cerebrospinal fluid cytokine concentration during postnatal development in the normal and jaundiced rat.Fluids and barriers of the CNS · 2022Article
- The Role of Bilirubin and the Other "Yellow Players" in Neurodegenerative Diseases.Antioxidants (Basel, Switzerland) · 2020Review
- Crigler-Najjar Syndrome Type 1: Pathophysiology, Natural History, and Therapeutic Frontier.Hepatology (Baltimore, Md.) · 2020Article
- Histone acetylation as a new mechanism for bilirubin-induced encephalopathy in the Gunn rat.Scientific reports · 2018Article
- Barriers to Drug Distribution into the Perinatal and Postnatal Brain.Pharmaceutical research · 2018Review
- Article
- Obstacles to Brain Tumor Therapy: Key ABC Transporters.International journal of molecular sciences · 2017Review
- Genetic and epigenetic changes in host ABCB1 influences malaria susceptibility to Plasmodium falciparum.PloS one · 2017Article
- Electroconvulsive shock attenuated microgliosis and astrogliosis in the hippocampus and ameliorated schizophrenia-like behavior of Gunn rat.Journal of neuroinflammation · 2016Article
- Unconjugated bilirubin elevation impairs the function and expression of breast cancer resistance protein (BCRP) at the blood-brain barrier in bile duct-ligated rats.Acta pharmacologica Sinica · 2016Article
- The Biological Effects of Bilirubin Photoisomers.PloS one · 2016Article
- Regulation of ABC efflux transporters at blood-brain barrier in health and neurological disorders.Brain research · 2015Review
- Efflux transporters in blood-brain interfaces of the developing brain.Frontiers in neuroscience · 2015Review
Corrections and comments
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Authors and funding
9 authors at 7 institutions in 3 countries.
Funding
Abstract
Accumulation of unconjugated bilirubin (UCB) in the brain causes bilirubin encephalopathy. Pgp (ABCb1) and Mrp1 (ABCc1), highly expressed in the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB) respectively, may modulate the accumulation of UCB in brain. We examined the effect of prolonged exposure to elevated concentrations of UCB on expression of the two transporters in homozygous, jaundiced (jj) Gunn rats compared to heterozygous, not jaundiced (Jj) littermates at different developmental stages (2, 9, 17 and 60 days after birth). BBB Pgp protein expression was low in both jj and Jj pups at 9 days (about 16-27% of adult values), despite the up-regulation in jj animals (2 and 1.3 fold higher than age matched Jj animals at P9 and P17-P60, respectively); Mrp1 protein expression was barely detectable. Conversely, at the BCSFB Mrp1 protein expression was rather high (60-70% of the adult values) in both jj and Jj at P2, but was markedly (50%) down-regulated in jj pups starting at P9, particularly in the 4(th) ventricle choroid plexuses: Pgp was almost undetectable. The Mrp1 protein down regulation was accompanied by a modest up-regulation of mRNA, suggesting a translational rather than a transcriptional inhibition. In vitro exposure of choroid plexus epithelial cells obtained from normal rats to UCB, also resulted in a down-regulation of Mrp1 protein. These data suggest that down-regulation of Mrp1 protein at the BSCFB, resulting from a direct effect of UCB on epithelial cells, may impact the Mrp1-mediated neuroprotective functions of the blood-cerebrospinal fluid barrier and actually potentiate UCB neurotoxicity.
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Registered trials
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.