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A Human Blood-Brain Interface Model to Study Barrier Crossings by Pathogens or Medicines and Their Interactions with the Brain
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Developmental differences in the expression of ABC transporters at rat brain barrier interfaces following chronic

Liam M Koehn1, Katarzyna M Dziegielewska1, Kjeld Møllgård2

  • 1Department of Pharmacology and Therapeutics, The University of Melbourne, Melbourne, Victoria, Australia.

Scientific Reports
|April 14, 2019
PubMed

Insights

Brain barriers develop age-dependent defense mechanisms, regulating drug transporters like ABC transporters and glutathione-s-transferase (GST) in response to xenobiotic compounds.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Developmental Biology

Background:

  • Drug transfer into the brain is restricted by ATP-binding cassette (ABC) transporters in adults.
  • These efflux mechanisms are less understood in developing brains of infants and children.
  • Medications are crucial for various conditions in pregnant women and premature infants.

Purpose of the Study:

  • To investigate the expression and regulation of ABC transporters and glutathione-s-transferase (GST) during postnatal rat brain development.
  • To compare these mechanisms in liver, brain cortex (blood-brain barrier), and choroid plexus (blood-cerebrospinal fluid barrier).
  • To assess the impact of chronic diallyl sulfide (DAS) exposure on these systems.

Main Methods:

  • Measured expression of eight ABC transporters and GST activity in rat tissues at different postnatal ages.
  • Administered chronic diallyl sulfide (DAS) to assess its inductive effects.
  • Utilized immunocytochemistry to visualize ABC transporter localization at the cerebrospinal fluid-brain interface.

Main Results:

  • Tissue- and age-dependent regulation of ABC transporters and GST was observed.
  • Liver showed consistent upregulation of abcb1a and abcc3.
  • Brain cortex and choroid plexus exhibited age-specific upregulation of various ABC transporters.
  • DAS increased GST activity in livers but not in brain barriers.
  • Specific ABC transporters (PGP, BCRP, MRP2/4/5) showed distinct localizations in brain barriers.

Conclusions:

  • Developing brain barriers possess dynamic, age-related capacities to regulate xenobiotic defense mechanisms.
  • Understanding these developmental changes is crucial for optimizing drug therapy in vulnerable populations.
  • The study highlights the differential regulation of drug efflux transporters during brain maturation.

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