Journal
BRAIN RESEARCH BULLETIN
Volume 139, Issue -, Pages 269-277Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.brainresbull.2018.03.001
Keywords
Blood-brain barrier; Aging; P-Glycoprotein; Imaging; Microdialysis
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Funding
- Faculty of Information Technology and Bionics, Pazmany Peter Catholic University, Budapest, Hungary
- European Union - European Social Fund [EFOP-3.6.3-VEKOP-16-2017-00002]
- New National Excellence Program of the Ministry of Human Capacities [UNKP- 17-4-I-PTE-76, UNKP-17-4-III-PTE-93]
- Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences [PTE AOK-KA-2017-05, PTE AOK-KA-2017-06]
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Decreased beta-amyloid clearance in Alzheimer's disease and increased blood-brain barrier permeability in aged subjects have been reported in several articles. However, morphological and functional characterization of blood-brain barrier and its membrane transporter activity have not been described in physiological aging yet. The aim of our study was to explore the structural changes in the brain microvessels and possible functional alterations of P-glycoprotein at the blood-brain barrier with aging. Our approach included MR imaging for anatomical orientation in middle aged rats, electronmicroscopy and immunohistochemistry to analyse the alterations at cellular level, dual or triple-probe microdialysis and SPECT to test P-glycoprotein functionality in young and middle aged rats. Our results indicate that the thickness of basal lamina increases, the number of tight junctions decreases and the size of astrocyte endfeet extends with advanced age. On the basis of microdialysis and SPECT results the P-gp function is reduced in old rats. With our multiparametric approach a complex regulation can be suggested which includes elements leading to increased permeability of blood-brain barrier by enhanced paracellular and transcellular transport, and factors working against it. To verify the role of P-gp pumps in brain aging further studies are warranted.
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