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Background:  Thyroxine (T 4 ) hormone is synthesized by the thyroid gland and then released into the systemic circulation where it binds to a number of proteins. Dysfunction in T 4  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 T 4  transport mechanisms, this study investigated the transfer of T 4  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 T 4  ( 125 I-T 4 ) was perfused continuously into the CSF and was assessed in several brain compartments with reference molecule  14 C-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  125 I-T 4 , was increased compared to controls, with concomitant increase in T 4  clearance. Conversely, brefeldin A, phloretin, and TA did not exert any significant effect on the recovery and clearance of  125 I-T 4  assessed in aCSF. On the other hand, the uptake of  125 I-T 4  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  125 I-T 4  by almost 3-fold, whereas TA did not show any significant effect. Finally, the uptake and distribution of  125 I-T 4  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  125 I-T 4  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).

frontiers in cell and developmental biology

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