Effects of transthyretin on thyroxine and ß-amyloid removal from cerebrospinal fluid in mice.

Chen, Ruoli; Chen, Carl P; Preston, Jane E

Abstract

Transthyretin (TTR) is a binding protein for the thyroid hormone thyroxine (T4 ), retinol and ß-amyloid peptide. TTR aids the transfer of T4 from the blood to the cerebrospinal fluid (CSF), but also prevents T4 loss from the blood-CSF barrier. It is however, unclear whether TTR affects the clearance of ß-amyloid from the CSF. This study aimed to investigate roles of TTR in ß-amyloid and T4 efflux from the CSF. Eight weeks old 129sv male mice were anaesthetized and their lateral ventricles were cannulated. Mice were infused with artificial CSF containing (125) I-T4 / (3) H-mannitol, or (125) I-Aß40 / (3) H-inulin, in present or absent of TTR. Mice were decapitated at 2, 4, 8, 16, 24 minutes after injection. The whole brain was then removed and divided into different regions. The radioactivities in the brain were determined by liquid scintillation counting. At baseline, the net uptake of (125) I-T4 into the brain was significantly higher than that of (125) I-Aß40, and the half time for efflux was shorter ((125) I-T4 : 5.16, (3) H-mannitol: 7.44; (125) I-Aß40: 8.34, (3) H-inulin: 10.78; mins). The presence of TTR increased the half time for efflux of (125) I-T4 efflux, and caused a noticeable increase in the uptake of (125) I-T4 and (125) I-Aß40 in the choroid plexus, whilst uptakes of (3) H-mannitol and (3) H-inulin remained similar to control experiments. This study indicates that thyroxine and amyloid peptide effuse from the CSF using different transporters. TTR binds to thyroxine and amyloid peptide to prevent the loss of thyroxine from the brain and redistribute amyloid peptide to the choroid plexus. This article is protected by copyright. All rights reserved.

Citation

Chen, R., Chen, C. P., & Preston, J. E. (2016). Effects of transthyretin on thyroxine and ß-amyloid removal from cerebrospinal fluid in mice. Clinical and Experimental Pharmacology and Physiology, 43(9), 844-850. https://doi.org/10.1111/1440-1681.12598

• Journal Article Type: Article
• Acceptance Date: May 20, 2016
• Publication Date: May 24, 2016
• Journal: Clin Exp Pharmacol Physiol
• Print ISSN: 0305-1870
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 43
• Issue: 9
• Pages: 844-850
• DOI: https://doi.org/10.1111/1440-1681.12598
• Keywords: choroid plexus; TTR; Thyroxine; B-amyloid; efflux; CSF; Alzheimers Disease
• Publisher URL: https://doi.org/10.1111/1440-1681.12598