AUTHOR=Zibara Kazem , El-Zein Ali , Joumaa Wissam , El-Sayyad Mohammad , Mondello Stefania , Kassem Nouhad TITLE=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 JOURNAL=Frontiers in Cell and Developmental Biology VOLUME=3 YEAR=2015 URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2015.00060 DOI=10.3389/fcell.2015.00060 ISSN=2296-634X ABSTRACT=

Background: Thyroxine (T₄) hormone is synthesized by the thyroid gland and then released into the systemic circulation where it binds to a number of proteins. Dysfunction in T₄ transport mechanisms has been demonstrated in multiple central nervous system (CNS) diseases including Alzheimer's disease. In the presence of different compounds that inhibit potential T₄ transport mechanisms, this study investigated the transfer of T₄ from cerebrospinal fluid (CSF) into Choroid Plexus (CP) and other brain tissues. The compounds used were brefeldin A, low sodium artificial CSF (aCSF), BCH, phloretin, and taurocholate (TA).

Methods: Radiolabeled T₄ (¹²⁵I-T₄) was perfused continuously into the CSF and was assessed in several brain compartments with reference molecule ¹⁴C-mannitol and blue dextran, using the in vivo ventriculo-cisternal perfusion (V-C) technique in the rabbit. The aCSF containing the drug of interest was infused after 1 h of perfusion. Drugs were applied independently to the aCSF after 1 h of control perfusion.

Results: Of interest, in presence of low sodium or BCH, the percentage recovery of ¹²⁵I-T₄, was increased compared to controls, with concomitant increase in T₄ clearance. Conversely, brefeldin A, phloretin, and TA did not exert any significant effect on the recovery and clearance of ¹²⁵I-T₄ assessed in aCSF. On the other hand, the uptake of ¹²⁵I-T₄ into CP was raised by 18 fold compared to controls in the presence of brefeldin A. In addition, low sodium, BCH, or phloretin alone, enhanced the uptake of ¹²⁵I-T₄ by almost 3-fold, whereas TA did not show any significant effect. Finally, the uptake and distribution of ¹²⁵I-T₄ into other brain regions including ependymal region (ER) and caudate putamen (CAP) were significantly higher than in controls.

Conclusion: Our study suggests the involvement of different mechanisms for the transfer of ¹²⁵I-T₄ from CSF into CP and other brain regions. This transfer may implicate sodium-dependent mechanisms, amino acid “L” system, or organic anion transporting polypeptide (OATP).