Metabolic fuel and amino acid transport into the brain in experimental hypothyroidism

The effect of hypothyroidism in the adult rat on blood-brain barrier and muscle transport of hexoses, neutral amino acids, basic amino acids, monocarboxylic acids, and ketone bodies was examined using single arterial injection-tissue sampling technique. The cerebral blood flow and brain extraction of 3H2O (internal reference substance) was not altered in 3-month-old hypothyroid rats maintained on methimazole, 0.025% in the drinking water, for 7 weeks. The brain uptake index of D-beta-hydroxybutyrate was significantly reduced in hypothyroid rats (2.4 +/- 0.3 vs 4.6 +/- 0.6% p less than 0.001). Hypothyroid rats given thyroid hormone replacement therapy had normal brain uptake of D-beta-hydroxybutyrate (4.4 +/- 0.8%). The brain uptake index of butyrate was also significantly reduced in hypothyroid rats (39.3 +/- 2.1 vs 47.2 +/- 0.74%, p less than 0.001). The brain uptake index of other test substances and muscle uptake of nutrients examined were not altered in hypothyroid rats. These studies indicate that of the four transport systems examined in two tissues, the blood-brain barrier monocarboxylic acid transport system is most susceptible to the hypothyroidism-induced changes.