Vascular and extravascular distribution of the ATP-binding cassette transporters ABCB1 and ABCC1 in aged human brain and pituitary

Mech Ageing Dev. 2014 Nov-Dec:141-142:12-21. doi: 10.1016/j.mad.2014.08.003. Epub 2014 Sep 10.

Abstract

ATP-binding cassette (ABC) transporters play an increasing role in the understanding of pathologic peptide deposition in neurodegenerative diseases (NDs), such as Alzheimer's and Parkinson's. To describe the location of the most important ABC transporters for NDs in human brain tissue, we investigated ABCB1 and ABCC1 immunohistologically in the adult human brain and pituitary. Both transporters have similar but not identical expression patterns. In brain regions with an established blood-brain barrier (BBB), ABCB1 and ABCC1 were ubiquitously expressed in endothelial cells of the microvasculature and in a subset of larger blood vessels (mostly venules). Remarkably, both transporters were also found in fenestrated capillaries in circumventricular organs where the BBB is absent. Moreover, ABCB1 and ABCC1 were also expressed in various non-endothelia cells such as pericytes, astrocytes, choroid plexus epithelia, ventricle ependymal cells, and neurons. With regard to their neuronal expression it was shown that both transporters are located in specific nerve cell populations, which are also immunopositive for three putative cell markers of purinergic cell signalling, namely 5'-nucleotidase, adenosine deaminase and nucleoside triphosphate diphosphohydrolase-2. Therefore, we speculate that neuronal expression of ABCB1 and ABCC1 might be linked to adenosinergic/purinergic neuromodulation. Lastly, both transporters were observed in multiple adenohypophyseal cells.

Keywords: ABC transporters; ATP-binding cassette sub-family B member 1 (ABCB1); ATP-binding cassette sub-family C member 1 (ABCC1); Blood–brain barrier; Circumventricular organs; Human brain; Human pituitary; Neurons; Purinergic signalling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / biosynthesis
  • Adult
  • Aging / metabolism*
  • Blood-Brain Barrier / metabolism*
  • Female
  • Gene Expression Regulation / physiology
  • Humans
  • Male
  • Middle Aged
  • Multidrug Resistance-Associated Proteins / biosynthesis*
  • Nerve Tissue Proteins / biosynthesis*
  • Pituitary Gland* / blood supply
  • Pituitary Gland* / metabolism

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • Multidrug Resistance-Associated Proteins
  • Nerve Tissue Proteins
  • multidrug resistance-associated protein 1