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

Article English OPEN
Chen, R ; Chen, CP ; Preston, JE (2016)
  • Publisher: Wiley
  • Related identifiers: doi: 10.1111/1440-1681.12598
  • Subject: Alzheimer's Disease | Thyroxine | TTR | CSF | RM | efflux | QP | R1 | choroid plexus | β-amyloid

Transthyretin (TTR) is a binding protein for the thyroid hormone thyroxine (T4 ), retinol and β-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 β-amyloid from the CSF. This study aimed to investigate roles of TTR in β-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-Aβ40 / (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-Aβ40, and the half time for efflux was shorter ((125) I-T4 : 5.16, (3) H-mannitol: 7.44; (125) I-Aβ40: 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-Aβ40 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.
  • References (52)
    52 references, page 1 of 6

    1. Alshehri B, D'Souza DG, Lee JY, Petratos S, Richardson SJ. The diversity of mechanisms influenced by transthyretin in neurobiology: development, disease and endocrine disruption. J. Neuroendocrinol. 2015; 27: 303-23.

    2. Dickson PW, Schreiber G. High levels of messenger RNA for transthyretin (prealbumin) in human choroid plexus. Neurosci. Lett. 1986; 66: 311-5.

    3. Dickson PW, Aldred AR, Marley PD, Bannister D, Schreiber G. Rat choroid plexus specializes in the synthesis and the secretion of transthyretin (prealbumin). Regulation of transthyretin synthesis in choroid plexus is independent from that in liver. J. Biol. Chem. 1986; 261: 3475-8.

    4. Fung WP, Thomas T, Dickson PW et al. Structure and expression of the rat transthyretin (prealbumin) gene. J. Biol. Chem. 1988; 263: 480-8.

    5. Hu S, Loo JA, Wong DT. Human body fluid proteome analysis. Proteomics 2006; 6: 6326-53.

    6. Southwell BR, Duan W, Alcorn D et al. Thyroxine transport to the brain: role of protein synthesis by the choroid plexus. Endocrinol. 1993; 133: 2116-26.

    7. Richardson SJ, Wijayagunaratne RC, D'Souza DG, Darras VM, van Herck SLJ. Transport of thyroid hormones via the choroid plexus into the brain: the roles of transthyretin and throid hormone transmemebrane transporters. Frontiers. Neurosci. 2005; 9: 1-8.

    8. Sousa JC, de Escobar GM, Oliveira P, Saraiva MJ, Palha JA. Transthyretin is not necessary for thyroid hormone metabolism in conditions of increased hormone demand. J.

    9. Palha JA, Hays MT, Morreale de Escobar G, Episkopou V, Gottesman ME, Saraiva MJ. Transthyretin is not essential for thyroxine to reach the brain and other tissues in transthyretin-null mice. Am. J. Physiol. 1997; 272: E485-93.

    10. Mendel CM. The free hormone hypothesis: a physiologically based mathematical model. Endocr. Rev. 1989; 10: 232-74.

  • Metrics
    No metrics available
Share - Bookmark