Μελέτη του ντοπαμινεργικού συστήματος στο ραβδωτό σώμα ενήλικων μυών στην κατάσταση του υποθυρεοειδισμού
Authors: Μανιάτη Σταματίνα 
Published: January 2014

Objectives: Thyroid hormones (T3 and T4) are necessary in differentiation and development but also in the maturation of the central neural system. Their action has been connected with alterations in behavior, as well as with psychological and movement disorders. It is known that the dopaminergic (DA) innervation of the basal ganglia, and in particular of the striatum, plays a central role in most movement, cognitive and emotional functions. Hypothyroidism induces morphological alterations, and more precisely, reductions in the axonal and dendritic sprouting of striatal neurons of adult rat brain and also modifications in the ability of dopamine antagonists’ ligand-binding. However, the underling mechanisms involved at the cellular and molecular level remain unidentified. Aim: In the current dissertation, we studied the effect of hypothyroidism in the striatum of adult, male Balb-c mice, in order to get a better understanding on the underling mechanism(s) of the effect of thyroid hormones on the DAergic system in adult brain. Results: Autoradiography showed a quantitative reduction in the level of D2 receptors in the basal ganglia of adult, male, hypothyroid mice versus that in eythyroid mice. Saturation studies revealed a non- statistically significant alteration in the chemical affinity of D2 receptor antagonist [3H]-raclopride for these receptors. However, a statistically significant reduction (37 %) in Bmax of the radiolabeled ligand was observed in D2 dopaminergic receptors of the hypothyroid mice versus the euthyroid. Similar studies on the pharmacological profile of D2 DAergic receptor binding, showed a statistically significant increase in the binding affinity of dopamine versus [3H]-raclopride, at the high affinity site, and a reduction in the percentage of the binding sites in this site, in the striatum of male, adult hypothyroid mice versus eythyroid. The opposite effect was observed in the low affinity site, where we showed a reduction in the binding affinity. Furthermore, the “in vitro” addition of T3 in striatal homogenates of male, adult euthyroid brain resulted in a statistically significant reduction in the binding affinity, of the high affinity site, compared to euthyroid samples. Also, by activation of A2A adenosine receptors through application of the CGS21680 agonist, a statistically significant reduction was observed in the binding affinity, when at the high affinity site, of the hypothyroid compared to eythyroid samples. Finally the effect of hypothyroidism in the induction of cAMP synthesis was also examined. Our data showed that the SKF38393 (a D1 dopamine receptor agonist)-driven cAMP synthesis is statistically significant in the striatum of adult, male hypothyroid mice and that the D1/D2 interaction system of dopamine receptors is different between euthyroid and hypothyroid mice. This means that when SKF38393-driven cAMP synthesis is suppressed by quinpirole (a D2 dopamine receptor agonist), a dose dependent inhibition is observed in the striatum of euthyroid mice, which is similar, but not proportional to the inhibition observed in the striatum of hypothyroid mice. While the CGS21680 (a #2# adenosine receptror agonist)- driven cAMP synthesis is statistically significant in the striatum of adult, male hypothyroid mice versus to euthyroid and that the A2A/D2 interaction system of adenosine/dopamine receptors is different between euthyroid and hypothyroid mice. Only in hypothyroid mice the A2A-diven cAMP synthesis is statistically suppressed in a dose dependent manner, by costimulation of D2.receptors. Conclusions: Our results show the effect of thyroid hormones on the number of DAergic receptors level and on their signal transduction levels, after dopamine receptors activation in the striatum of adult, male mice. These observations mark the involvement of thyroid hormones in the interactions of the DAergic receptors with the adenosinergic receptors, both at the receptor-receptor and the signal transduction level.