Volume 8 Supplement 1

14th Scientific Symposium of the Austrian Pharmacological Society (APHAR)

Open Access

Decreased blood-brain barrier P-glycoprotein function with aging

  • Martin Bauer1,
  • Rudolf Karch2,
  • Aiman Abrahim1, 3,
  • Claudia C Wagner1,
  • Kurt Kletter4,
  • Markus Müller1 and
  • Oliver Langer1, 3Email author
BMC Pharmacology20088(Suppl 1):A48

https://doi.org/10.1186/1471-2210-8-S1-A48

Published: 5 November 2008

Introduction

P-glycoprotein (P-gp) acts at the blood-brain barrier (BBB) as an active cell membrane efflux pump for several endogenous and exogenous compounds. The P-gp substrate (R)-[11C]verapamil (VPM) can be used to measure P-gp-mediated transport at the BBB in vivo with positron emission tomography (PET). The distribution volume (DV) of VPM has been shown to inversely reflect P-gp function in the BBB [1].

Materials and methods

A young (n = 7, mean age: 28.0 ± 3.8 years) and an aged group (n = 6, mean age: 69.4 ± 8.5 years) of healthy volunteers underwent dynamic VPM PET scans and arterial blood sampling. Radiolabelled metabolites of VPM were quantified by a previously described combined solid-phase extraction/HPLC protocol [1]. A whole-brain grey matter region was defined by using the Hammersmith n20r49 brain atlas [2]. The DV of VPM was estimated by using a 2-rate-constant-1-tissue-compartment model [1].

Results

Mean DV s (± standard deviation) of VPM were 0.50 ± 0.08 for the young and 0.63 ± 0.13 for the aged group (+27% for the aged group, p = 0.04, 2-tailed t-test). There was no significant difference in VPM metabolism between the young and the aged group (area under the curve of the fraction of polar [11C]metabolites of VPM versus time in arterial plasma: 12.7 ± 2.4 and 14.1 ± 3.6 for the young and the aged group, respectively, p = 0.19, 2-tailed t-test).

Conclusion

Our data confirm previous results that older subjects show significantly decreased P-gp function in the BBB [1, 3]. Decreased P-gp function can lead to increased accumulation of toxins and drugs in the aging brain and could thus be a risk factor for the development of neurodegenerative disease.

Authors’ Affiliations

(1)
Department of Clinical Pharmacology, Medical University of Vienna
(2)
Department of Medical Computer Sciences, Medical University of Vienna
(3)
Department of Radiopharmaceuticals, Austrian Research Centers GmbH – ARC
(4)
Department of Nuclear Medicine, Medical University of Vienna

References

  1. Toornvliet R, van Berckel BN, Luurtsema G, Lubberink M, Geldof AA, Bosch TM, Oerlemans R, Lammertsma AA, Franssen EJ: Effect of age on functional P-glycoprotein in the blood-brain barrier measured by use of (R)-[11C]verapamil and positron emission tomography. Clin Pharmacol Ther. 2006, 79: 540-548. 10.1016/j.clpt.2006.02.004.View ArticlePubMedGoogle Scholar
  2. Hammers A, Allom R, Koepp MJ, Free SL, Myers R, Lemieux L, Mitchell TN, Brooks DJ, Duncan JS: Three-dimensional maximum probability atlas of the human brain, with particular reference to the temporal lobe. Hum Brain Mapp. 2003, 19: 224-247. 10.1002/hbm.10123.View ArticlePubMedGoogle Scholar
  3. Bartels AL, Kortekaas R, Bart J, Willemsen AT, de Klerk OL, de Vries JJ, van Oostrom JC, Leenders KL: Blood-brain barrier P-glycoprotein function decreases in specific brain regions with aging: A possible role in progressive neurodegeneration. Neurobiol Aging.Google Scholar

Copyright

© Bauer et al; licensee BioMed Central Ltd. 2008

This article is published under license to BioMed Central Ltd.

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