ArticlePhysiological reports2016
Astrocyte-mediated regulation of multidrug resistance p-glycoprotein in fetal and neonatal brain endothelial cells: age-dependent effects.
Article in Physiological reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 17 citations in OpenAlex.
- The role of the blood-brain barrier during neurological disease and infection.Biochemical Society transactions · 2023Review
- Article
- ATP-binding cassette (ABC) drug transporters in the developing blood-brain barrier: role in fetal brain protection.Cellular and molecular life sciences : CMLS · 2022Review
- Fetal glucocorticoid exposure leads to sex-specific changes in drug-transporter function at the blood-brain barrier in juvenile guinea pigs.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Sex-Dependent Gliovascular Interface Abnormality in the Hippocampus following Postnatal Immune Activation in Mice.Developmental neuroscience · 2022Article
- Astrocyte Activation in Neurovascular Damage and Repair Following Ischaemic Stroke.International journal of molecular sciences · 2021Review
- Function of Multidrug Resistance Transporters is Disrupted by Infection Mimics in Human Brain Endothelial Cells.Tissue barriers · 2021Article
- Excess glutamate secreted from astrocytes drives upregulation of P-glycoprotein in endothelial cells in amyotrophic lateral sclerosis.Experimental neurology · 2019Article
- Mind the Gaps: Ontogeny of Human Brain P-gp and Its Impact on Drug Toxicity.The AAPS journal · 2019Review
- The myth of the immature barrier systems in the developing brain: role in perinatal brain injury.The Journal of physiology · 2018Review
- Barriers to Drug Distribution into the Perinatal and Postnatal Brain.Pharmaceutical research · 2018Review
- Drug Transport at the Brain and Endothelial Dysfunction in Preeclampsia: Implications and Perspectives.Frontiers in physiology · 2018Article
- Astrocyte-mediated regulation of multidrug resistance p-glycoprotein in fetal and neonatal brain endothelial cells: age-dependent effects.Physiological reports · 2016Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Brain endothelial cells (BECs) form a major component of the blood-brain barrier (BBB). In late gestation, these cells express high levels of the multidrug transporter p-glycoprotein (P-gp; encoded by Abcb1), which prevents the passage of an array of endogenous factors and xenobiotics into the fetal brain. P-gp levels in the BECs increase dramatically in late gestation, coincident with astrocyte differentiation. However, the role of astrocytes in modulating P-gp in the developing BBB is unknown. We hypothesized that factors produced by astrocytes positively regulate P-gp in BECs. Astrocytes and BECs were isolated from fetal and postnatal guinea pigs. Levels of Abcb1 mRNA and P-gp were increased in BECs co-cultured with astrocytes compared to BECs in monoculture. Moreover, postnatal astrocytes enhanced P-gp function in fetal BECs but fetal astrocytes had no effect on postnatal BECs. These effects were dependent on secreted proteins with a molecular weight in the range of 3-100 kDa. LC/MS-MS revealed significant differences in proteins secreted by fetal and postnatal astrocytes. We propose that astrocytes are critical modulators of P-gp at the developing BBB. As such, aberrations in astrocyte maturation, observed in neurodevelopmental disorders, will likely decrease P-gp at the BBB. This would allow increased transfer of P-gp endogenous and exogenous substrates into the brain, many of which have neurodevelopmental consequences.
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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.