期刊
NEUROSCIENCE LETTERS
卷 464, 期 1, 页码 47-51出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2009.08.014
关键词
P-glycoprotein; Multidrug transporter; Blood-brain barrier; Pharmacoresistance; siRNA; Epilepsy
资金
- German Research Foundation [DFG PO 681/4-1]
Over-expression of blood-brain barrier P-glycoprotein is considered as a major hurdle in the treatment of various CNS disorders. A down-regulation strategy is considered as one means to counteract disease- or therapy-associated induction of P-glycoprotein. Here, we evaluated whether a targeting P-glycoprotein can be achieved in mouse brain capillary endothelial cells using siRNA. A 4-day treatment paradigm with once daily hydrodynamic intravenous injections of siRNA resulted in a significant reduction of the P-glycoprotein-labeled area in the hippocampal hilus and parietal cortex. P-glycoprotein expression proved to be down-regulated in these brain regions by 31 and 16%, respectively. An impact of siRNA administration on density of brain capillaries was excluded by quantification of the endothelial cell marker GLUT-1. In conclusion, the study provides first preliminary evidence that a down-regulation ofP-glycoprotein can be achieved in brain capillary endothelial cells by administration of siRNA in vivo. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
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