Decrease of Transthyretin Synthesis at the Blood–Cerebrospinal Fluid Barrier of Old Sheep

Transthyretin (TTR), synthesized by the choroid plexus (CP) and secreted into cerebrospinal fluid (CSF), is involved in thyroxine (T4) transport and chelation of β-amyloid peptide, attenuating neurotoxicity. To characterize age-related changes in TTR synthesis, CSF and CPs were collected from young...

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Bibliographic Details
Published in:The journals of gerontology. Series A, Biological sciences and medical sciences Biological sciences and medical sciences, 2005-07, Vol.60 (7), p.852-858
Main Authors: Chen, Ruo L., Athauda, Senarath B. P., Kassem, Nouhad A., Zhang, Yi, Segal, Malcolm B., Preston, Jane E.
Format: Article
Language:English
Subjects:
Aging
Aging - physiology
Alzheimer's disease
Amyloid beta-Peptides - metabolism
Animals
Biological Transport - physiology
Biomarkers - blood
Biomarkers - cerebrospinal fluid
Blood-Brain Barrier - metabolism
Blotting, Northern
Blotting, Western
Choroid Plexus - metabolism
Electrophoresis, Agar Gel
Gene Expression Regulation
Iodine Radioisotopes
Nervous system
Polymerase Chain Reaction
Prealbumin - biosynthesis
Prealbumin - cerebrospinal fluid
Prealbumin - genetics
Proteins
Ribonucleic acid
RNA
RNA, Messenger - metabolism
Sheep
Spectrophotometry
Thyroxine - metabolism
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Summary:Transthyretin (TTR), synthesized by the choroid plexus (CP) and secreted into cerebrospinal fluid (CSF), is involved in thyroxine (T4) transport and chelation of β-amyloid peptide, attenuating neurotoxicity. To characterize age-related changes in TTR synthesis, CSF and CPs were collected from young adult (1–2 years) and old (>8 years) sheep anesthetized with thiopentone sodium. TTR in old sheep CSF was low compared to young (n = 4 each); however, CP messenger RNA (mRNA) for TTR did not change. CPs were perfused with Ringer containing 14C-leucine to assess de novo protein synthesis, or with 125I-T4 to assess T4 transport. Protein synthesis, including TTR, was reduced in old sheep CP and in newly secreted CSF. 125I-T4 Vmax and Kd (but not Km) were reduced in old sheep CP. These age-related changes suggest reduced capacity of CP to maintain CSF T4 homeostasis and could also reduce chelation of β-amyloid and be an added risk for Alzheimer's disease.
ISSN:1079-5006
1758-535X
DOI:10.1093/gerona/60.7.852