title: Role of transthyretin in thyroxine transfer from cerebrospinal fluid to brain and choroid plexus.
abstract: The transport of 125I-labeled thyroxine (T4) from the cerebrospinal fluid (CSF) into brain and choroid plexus (CP) was measured in anesthetized rabbit [0.5 mg/kg medetomidine (Domitor) and 10 mg/kg pentobarbitonal sodium (Sagatal) iv] using the ventriculocisternal (V-C) perfusion technique. 125I-labeled T4 contained in artificial CSF was continually perfused into the lateral ventricles for up to 4 h and recovered from the cisterna magna. The %recovery of 125I-labeled T4 from the aCSF was 47.2+/-5.6% (n=10), indicating removal of 125I-labeled T4 from the CSF. The recovery increased to 53.2+/-6.3% (n=4) and 57.8+/-14.8% (n=3), in the presence of 100 and 200 microM unlabeled-T4, respectively (P<0.05), indicating a saturable component to T4 removal from CSF. There was a large accumulation of 125I-labeled T4 in the CP, and this was reduced by 80% in the presence of 200 microM unlabeled T4, showing saturation. In the presence of the thyroid-binding protein transthyretin (TTR), more 125I-labeled T4 was recovered from CSF, indicating that the binding protein acted to retain T4 in CSF. However, 125I-labeled T4 uptake into the ependymal region (ER) of the frontal cortex also increased by 13 times compared with control conditions. Elevation was also seen in the hippocampus (HC) and brain stem. Uptake was significantly inhibited by the presence of endocytosis inhibitors nocodazole and monensin by >50%. These data suggest that the distribution of T4 from CSF into brain and CP is carrier mediated, TTR dependent, and via RME. These results support a role for TTR in the distribution of T4 from CSF into brain sites around the ventricular system, indicating those areas involved in neurogenesis (ER and HC).
authors.affiliation: King's College London, Institute of Gerontology and Wolfson Centre for Age Related Diseases, Hodgkin Bldg., Guy's Hospital Campus, London SE1 1UL, UK. nouhad.kassem@kcl.ac.uk
authors.forename: Nouhad A
authors.initials: NA
authors.lastname: Kassem
authors.forename: Rashid
authors.initials: R
authors.lastname: Deane
authors.forename: Malcolm B
authors.initials: MB
authors.lastname: Segal
authors.forename: Jane E
authors.initials: JE
authors.lastname: Preston
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002831:Choroid Plexus / Q000378:metabolism*; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology; D004805:Ependyma / Q000502:physiology; D005260:Female; D008297:Male; D008985:Monensin / Q000494:pharmacology; D015739:Nocodazole / Q000494:pharmacology; D011228:Prealbumin / Q000502:physiology*; D011817:Rabbits; D013974:Thyroxine / Q000134:cerebrospinal fluid* / Q000378:metabolism*; D013997:Time Factors
chemical_list: D011228:Prealbumin; D008985:Monensin; D013974:Thyroxine; D015739:Nocodazole