Disease-Induced Alterations in Brain Drug Transporters in Animal Models of Alzheimer's Disease
Kati-Sisko Vellonen, Jouni Ihalainen, Marie-Christine Boucau, Fabien Gosselet, Theo Picardat, Mikko Gynther, Katja M Kanninen, Anthony R White, Tarja Malm, Jari Koistinaho, Markus M Forsberg, Marika Ruponen
Pharmaceutical Research | SPRINGER/PLENUM PUBLISHERS | Published : 2017
PURPOSE: Alzheimer's disease (AD) may disturb functions of the blood-brain barrier and change the disposition of drugs to the brain. This study assessed the disease-induced changes in drug transporters in the brain capillaries of transgenic AD mice. METHODS: Eighteen drug transporters and four tight junction-associated proteins were analyzed by RT-qPCR in cortex, hippocampus and cerebellum tissue samples of 12-16-month-old APdE9, Tg2576 and APP/PS1 transgenic mice and their healthy age-matched controls. In addition, microvessel fractions enriched from 1-3-month-old APdE9 mice were analyzed using RT-qPCR and Western blotting. Brain transport of methotrexate in APdE9 mice was assessed by in vi..View full abstract
Awarded by Academy of Finland
This study was funded by Academy of Finland (Grant number 257386). Finnish Cultural Foundation is also acknowledged for financial support. KMK and TM acknowledges the funding from the Academy of Finland and Sigrid Juselius Foundation. We thank Dr. Aaro Jalkanen for advice in designing microdialysis experiment, Prof. Seppo Auriola for consultation in LC-MS/MS analysis and Lecturer Veli-Pekka Ranta for advice regarding pharmacokinetics. Mrs. Jaana Leskinen, Mrs. Leena Pietila and Mrs. Lea Pirskanen are acknowledged for technical assistance. The authors declare that they have no conflict of interest. All applicable international, national and institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the University of Eastern Finland or practice at which the studies were conducted. This article does not contain any studies with human participants performed by any of the authors.