BMC Pharmacology

, 8:A48 | Cite as

Decreased blood-brain barrier P-glycoprotein function with aging

  • Martin Bauer
  • Rudolf Karch
  • Aiman Abrahim
  • Claudia C Wagner
  • Kurt Kletter
  • Markus Müller
  • Oliver Langer
Open Access
Meeting abstract

Keywords

Positron Emission Tomography Verapamil Distribution Volume Aged Group Positron Emission Tomography Scan 

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.

References

  1. 1.
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    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.CrossRefPubMedGoogle Scholar
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    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 information

© Bauer et al; licensee BioMed Central Ltd. 2008

This article is published under license to BioMed Central Ltd.

Authors and Affiliations

  • Martin Bauer
    • 1
  • Rudolf Karch
    • 2
  • Aiman Abrahim
    • 1
    • 3
  • Claudia C Wagner
    • 1
  • Kurt Kletter
    • 4
  • Markus Müller
    • 1
  • Oliver Langer
    • 1
    • 3
  1. 1.Department of Clinical PharmacologyMedical University of ViennaViennaAustria
  2. 2.Department of Medical Computer SciencesMedical University of ViennaViennaAustria
  3. 3.Department of RadiopharmaceuticalsAustrian Research Centers GmbH – ARCSeibersdorfAustria
  4. 4.Department of Nuclear MedicineMedical University of ViennaViennaAustria

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