Two hundred undergraduate students participated in a repeated-trials binary choice procedure in which choice of one outcome was correct on 75% of trials. Subjects received 192 trials and were divided into five conditions: (1) control; (2) subjects were given the actual probabilities; (3) subjects were told if they did well they could leave early; (4) competition condition;(5) midway through the task subjects were asked to recommend a strategy for another subject. Hall of the subjects in each group were told that the best they could do was to be correct on 75% of the trials. This manipulation permitted assessment of the hypothesis that subjects in probability-matching tasks are seeMng a strategy that will be correct on 100% of the trials. The results partially confirmed this hypothesis. In addition, two of the variables improved performance significantly (giving probabilities and asking subjects to recommend a strategy). However, while subjects in all groups improved significantly over trials, optimal choice did not occur in this task.

Thyroid hormones and retinoic acid (RA) are important modulators of growth, development, and differentiation. Type III deiodinase (D-III), which catalyzes thyroid hormones degradation in the brain and in cultured astroglial cells, is induced in astroglial cells by multiple pathways, including cAMP, 12.0-tetradecanoylphorbol-13-acetate (TPA), fibroblast growth factors, and thyroid hormones themselves. In the present study, the effects of retinoids on D-III activity were examined in astroglial cells cultures in a chemically defined medium devoid of hormones and growth factors. Incubation of astroglial cells with 5 microM all-trans-RA caused up to 200-fold increase in D-III activity, which reached a plateau after 48 h. The retinoid-induced increase in D-III activity was concentration dependent (0.5 microM all-trans-RA and 9-cis-RA producing half-maximal effect). Retinol was effective at physiological concentrations (1 and 10 microM). The 48 h effects of 5 microM all-trans-RA and 10 nM thyroid hormones on D-III activity were at least additive. Addition of 2 nM acidic fibroblast growth factor or 1 mM 8-bromo-cAMP for the last 8 h of a 48 h incubation with 5 microM all-trans-RA did not alter the induction by all-trans-RA, whereas 0.1 microM TPA in the same conditions produced an additive effect with all-trans-RA. All-trans-RA (5 microM) had little or no effect on type II deiodinase, the enzyme which catalyzes the activation of thyroxine to 3,5,3'-triiodothyronine.(ABSTRACT TRUNCATED AT 250 WORDS)

A type III iodothyronine deiodinase (D-III) that inactivates thyroid hormones has been recently cloned and identified as a selenoprotein in neonatal rat skin. However, selenium (Se) deficiency does not affect the D-III activity in the rat placenta and decreases the D-III in the rat brain only slightly. This study examines the effect of Se on the D-III activity in cultures of rat brain astrocytes. Astrocytes were depleted in Se by maintaining them in Se-free chemically defined medium for 7 days. These conditions decreased the activity of a recognized selenoprotein, glutathione peroxidase, 3-10-fold. D-III activity induced by 12-0-tetradecanoylphorbol-13-acetate (TPA) was also decreased 2-6-fold. Addition of 30 nM Se to the culture medium caused a rapid increase in TPA-induced D-III activity visible within 1 h. This Se effect was maximal at 3 h (4-fold increase) and dose-dependent. Se also increased the induction of D-III by acidic Fibroblast Growth Factor, 8-bromo-cAMP, T4, or retinoic acid. Cycloheximide blocked the effect of Se on TPA-induced D-III activity, whereas actinomycin D did not. Thus the rapid effect of Se does not require messenger RNA synthesis but requires protein synthesis. We conclude that the D-III in astrocytes is probably a selenoprotein.

The type III deiodinase (D-III) activity in astroglial cells is induced by multiple pathways activated by cAMP, 12-O-tetradecanoylphorbol-13-acetate (TPA), and fibroblast growth factors (FGFs). This study examines the effects of thyroid hormones on D-III activity in astroglial cells with or without induction by these factors. Addition of 10 nM T3 to the culture medium caused a slow increase in D-III activity, which reached a plateau after 48 h. This increase was concentration dependent (maximal response at 10 nM). Doses as low as 0.3 nM caused significant increases in D-III activity. The effect of T3 was reversible. A dose of 10 nM L-T3, D-T3, T4, 3,5,3'-triiodothyroacetic, or 3'-isopropyl-3,5-diiodothyronine produced 5- to 15-fold increases in D-III activity after 48 h. In contrast, 10 nM L-thyronine, 3-monoiodothyronine, 3,3'-diiodothyronine, 3,5-diiodothyronine, and rT3 were without effect. A dose of 10 nM T3 or T4 amplified the D-III activity stimulated by 0.1 microM TPA, 20 ng/ml acidic FGF, or 1 mM 8-bromo-cAMP 3- to 8-fold. Otherwise, T3 rapidly inhibited D-II activity. This inhibition was concentration dependent, with a half-maximal effect around 10 nM. In conclusion, thyroid hormones induce D-III activity and potentiate the D-III activity induced by cAMP, TPA, and FGFs in astroglial cells. These reversible effects together with inhibition of D-II activity may contribute to protect the brain against hyperthyroidism.

We describe the effects of the neurotoxin 3-nitropropionic acid (3-NPA) on fatty acid oxidation in neonatal rat brain astrocytes in primary culture, using a sensitive assay for β-oxidation which depends on the release of ³H₂O from [9,10(n)-³H]palmitic acid. 3-NPA is a suicide inhibitor of succinate dehydrogenase, a constituent of both Krebs cycle and complex II of the mitochondrial respiratory chain. It is widely distributed in plants and fungi. Neurotoxicity of 3-NPA to humans and animals, leading to selective neuronal cell death, appears mediated by the reduced level of ATP induced by the toxin. We demonstrated that 3-NPA can also impair energy metabolism in astrocytes. Exposure of astroglial cells in culture to 3-NPA leads to inhibition of the release of ³H₂O from [9,10(n)-3H]palmitic acid. Addition of 2 mM 3-NPA to the culture medium caused a rapid decrease in β-oxidation activity, which reached a plateau after 90 min. This inhibition was concentration-dependent. Concentration as low as 0.05 mM for 5 h significantly decreased β-oxidation activity (25% inhibition). Half-maximal inhibition was obtained after treatment with 0.5 mM 3-NPA, and 3 mM induced a maximal response (63% inhibition). 3-NPA is clearly a potent inhibitor of β-oxidation activity. We also show that 3-NPA 3 mM inhibits partially complex II (succinate ubiquinone reductase) and aspartate aminotransferase by 60 and 49% after 4 h treatment respectively. It has been shown that fatty acid is the preferred substrate for energy production in cultured astrocytes from developing brain. As astrocytes may also provide substrate alternative for energy metabolism in neurons and oligodendrocytes, it is likely that the inhibition of β-oxidation by 3-NPA may contribute significantly to the damage induced by this toxin in the central nervous system.