Dietary goitrogen-induced changes in the transport of 2-deoxy-d-glucose and amino acids across the rat blood-brain barrier

Abstract

The hypothesis that a defect in the rate-limiting blood-brain barrier (BBB) nutrient transport may be one of the factors responsible for the brain defects seen in some iodine deficiency disorders was tested in Wistar/NIN rats fed potassium thiocyanate (KSCN), a synthetic goitrogen. The BBB nutrient transport was measured by the brain uptake index (BUI) method. Feeding KSCN to female rats (from weaning) through their growth, pregnancy and lactation (G1) but not from conception (G2) or parturition (G3) resulted in a significant decrease (≈23%) in the BBB transport of 2-deoxy-d-glucose (2-DG) in their offspring at weaning, compared with controls (C). Post-weaning KSCN-feeding (G4) of control pups did not affect their BBB 2-DG transport (BUI: 36.2±4.98, vs 38.8±4.11). The effects of different KSCN regimens on BBB transport of leucine (leu), tyrosine (tyr) and sucrose (background marker) were inconsistent, of smaller magnitude (≈10%) and appeared to be of little significance. Withdrawing KSCN from the diet of chronically KSCN-fed (G1) mothers from conception (G5) or parturition (G6) prevented the impairment of BBB 2-DG transport in pups (BUI: 27.0±4.98, 20.8±3.27, 26.9±3.99 and 28.3±3.47 in C, G1, G5 and G6 pups, respectively); this was reversed by feeding the control diet to G1 pups from weaning. Withdrawal of dietary KSCN did not affect BBB transport of leu, tyr and sucrose. The decreased BBB transport of 2-DG in G1 pups appears to be due to a decrease in affinity (Kt app 5.46 vs 4.15 mM) rather than in the capacity (Tmax app 0.94 vs 0.91 μmoles/g/min) of the transport system. Intracarotid injections of KSCN per se had no effect on BBB 2-DG transport, suggesting that the effects may be secondary to the altered thyroid status of the animal.