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 beta-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 beta-amyloid and be an added risk for Alzheimer's disease.
Chen
Ruo L
RL
Institute of Gerontology, Franklin-Wilkins Building, King's College, 150 Stamford Street, London SE1 9NH. ronnie.chen@kcl.ac.uk
Athauda
Senarath B P
SB
Kassem
Nouhad A
NA
Zhang
Yi
Y
Segal
Malcolm B
MB
Preston
Jane E
JE
D000375:Aging / Q000502:physiology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D001812:Blood-Brain Barrier / Q000378:metabolism*; D015152:Blotting, Northern; D015153:Blotting, Western; D002831:Choroid Plexus / Q000378:metabolism*; D004587:Electrophoresis, Agar Gel; D005786:Gene Expression Regulation; D007457:Iodine Radioisotopes; D016133:Polymerase Chain Reaction; D011228:Prealbumin / Q000096:biosynthesis* / Q000134:cerebrospinal fluid / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D012756:Sheep; D013053:Spectrophotometry; D013974:Thyroxine / Q000378:metabolism
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D007457:Iodine Radioisotopes; D011228:Prealbumin; D012333:RNA, Messenger; D013974:Thyroxine