Thyroxine transfer from cerebrospinal fluid into choroid plexus and brain is affected by brefeldin A, low sodium, BCH, and phloretin, in ventriculo-cisternal perfused rabbits

Zibara, Kazem; El-Zein, Ali; Joumaa, Wissam H.; El-Sayyad, Mohammad; Mondello, Stefania; Kassem, Nouhad

doi:10.3389/fcell.2015.00060

Cited by 3 publications

(3 citation statements)

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“…The steady-state extraction of 125 I-T 4 at the blood side (basolateral) of the perfused CP over 1 h was calculated relative to the extracellular marker 14 C-mannitol. This allows to measure the extraction of 125 I-T 4 in presence of drugs known to inhibit the efflux transporters, at the basolateral side of the CP, such as probenecid, verapamil, BCH, and indomethacin ( 24 , 25 ). The net extraction of 125 I-T 4 from the blood to CP, which represents the non-specific paracellular loss of T 4 , was calculated by subtracting the extraction of 14 C-mannitol from that of 125 I-T 4 (Ex.…”

Section: Resultsmentioning

confidence: 99%

Thyroxine (T4) Transfer from Blood to Cerebrospinal Fluid in Sheep Isolated Perfused Choroid Plexus: Role of Multidrug Resistance-Associated Proteins and Organic Anion Transporting Polypeptides

et al. 2017

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Thyroxine (T4) enters the brain either directly across the blood–brain barrier (BBB) or indirectly via the choroid plexus (CP), which forms the blood–cerebrospinal fluid barrier (B-CSF-B). In this study, using isolated perfused CP of the sheep by single-circulation paired tracer and steady-state techniques, T4 transport mechanisms from blood into lateral ventricle CP has been characterized as the first step in the transfer across the B-CSF-B. After removal of sheep brain, the CPs were perfused with 125I-T4 and 14C-mannitol. Unlabeled T4 was applied during single tracer technique to assess the mode of maximum uptake (Umax) and the net uptake (Unet) on the blood side of the CP. On the other hand, in order to characterize T4 protein transporters, steady-state extraction of 125I-T4 was measured in presence of different inhibitors such as probenecid, verapamil, BCH, or indomethacin. Increasing the concentration of unlabeled-T4 resulted in a significant reduction in Umax%, which was reflected by a complete inhibition of T4 uptake into CP. In fact, the obtained Unet% decreased as the concentration of unlabeled-T4 increased. The addition of probenecid caused a significant inhibition of T4 transport, in comparison to control, reflecting the presence of a carrier mediated process at the basolateral side of the CP and the involvement of multidrug resistance-associated proteins (MRPs: MRP1 and MRP4) and organic anion transporting polypeptides (Oatp1, Oatp2, and Oatp14). Moreover, verapamil, the P-glycoprotein (P-gp) substrate, resulted in ~34% decrease in the net extraction of T4, indicating that MDR1 contributes to T4 entry into CSF. Finally, inhibition in the net extraction of T4 caused by BCH or indomethacin suggests, respectively, a role for amino acid “L” system and MRP1/Oatp1 in mediating T4 transfer. The presence of a carrier-mediated transport mechanism for cellular uptake on the basolateral membrane of the CP, mainly P-gp and Oatp2, would account for the efficient T4 transport from blood to CSF. The current study highlights a carrier-mediated transport mechanism for T4 movement from blood to brain at the basolateral side of B-CSF-B/CP, as an alternative route to BBB.

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Section: Resultsmentioning

confidence: 99%

Thyroxine (T4) Transfer from Blood to Cerebrospinal Fluid in Sheep Isolated Perfused Choroid Plexus: Role of Multidrug Resistance-Associated Proteins and Organic Anion Transporting Polypeptides

et al. 2017

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“…The increased accumulation of T 4 in the CP by TTR may be due to reduced basolateral efflux (from choroid epithelial cells to plasma) as well as an augmented uptake of T 4 from CSF. The T 4 efflux from the CSF involves a number of transporters and is saturable in presence of unlabelled T 4 . Despite the important role of TTR in TH homeostasis, mice lacking the TTR gene maintain normal functioning of thyroid glands in the face of significant reduction in total serum T 4 concentration .…”

Section: Discussionmentioning

confidence: 99%

“…The increased accumulation of T 4 in the CP by TTR may be due to reduced basolateral efflux (from choroid epithelial cells to plasma) as well as an augmented uptake of T 4 from CSF. The T 4 efflux from the CSF involves a number of transporters 29 and is saturable in presence of unlabelled Using the same model it was found that TTR was not essential for TH to reach the brain. 8 This is not surprising given there are numerous mechanisms for T 4 transport, and a number of TBG may take over the role of TTR in TTR-null mice.…”

Section: Effects Of Ttr On 125 I-t 4 / 125 I-aβ40 In the Brainmentioning

confidence: 98%

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

Chen

Preston

2016

Clin Exp Pharma Physio

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Transthyretin (TTR) is a binding protein for the thyroid hormone thyroxine (T 4 ), retinol and β-amyloid peptide. TTR aids the transfer of T 4 from the blood to the cerebrospinal fluid (CSF), but also prevents T 4 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 T 4 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

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Traversing barriers – How thyroid hormones pass placental, blood-brain and blood-cerebrospinal fluid barriers

Landers

Richard

2017

Molecular and Cellular Endocrinology

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Please cite this article as: Landers, K., Richard, K., Traversing barriers -How thyroid hormones pass placental, blood-brain and blood-cerebrospinal fluid barriers, Molecular and Cellular Endocrinology (2017), doi: 10.1016/j.mce.2017.01.041. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Thyroid hormone is essential for normal human fetal growth and brain development.

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Thyroxine transfer from cerebrospinal fluid into choroid plexus and brain is affected by brefeldin A, low sodium, BCH, and phloretin, in ventriculo-cisternal perfused rabbits

Cited by 3 publications

References 59 publications

Thyroxine (T4) Transfer from Blood to Cerebrospinal Fluid in Sheep Isolated Perfused Choroid Plexus: Role of Multidrug Resistance-Associated Proteins and Organic Anion Transporting Polypeptides

Thyroxine (T4) Transfer from Blood to Cerebrospinal Fluid in Sheep Isolated Perfused Choroid Plexus: Role of Multidrug Resistance-Associated Proteins and Organic Anion Transporting Polypeptides

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

Traversing barriers – How thyroid hormones pass placental, blood-brain and blood-cerebrospinal fluid barriers

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