Alterations of thyroidal status in brain regions and hypothalamo-pituitary-blood-thyroid-axis associated with dopaminergic depletion in substantia nigra and ROS formation in different brain regions after MPTP treatment in adult male mice

Abstract

MPTP produces oxidative stress, damages niagrostriatal dopaminergic neurons and develops Parkinsonism in rodents. Due to paucity of information, the thyroidal status in brain regions and peripheral tissues during different post-treatment days in MPTP-induced mice had been executed in the present study. MPTP depleted tyrosine hydroxylase protein expressions that signify the dopaminergic neuronal damage in substantia nigra. MPTP elevated ROS formation differentially in brain regions (cerebral cortex, hippocampus, substantia nigra) with maximal elevation at hippocampus. The changes in thyroid hormone (T₄ and T₃) levels indicate that brain regions might combat the adverse situation by keeping the levels of thyroid hormones either unchanged or in the elevated conditions in the latter phases (day-3 and day-7), apart from the depletion of thyroid hormones in certain brain regions (T₄ in SN and hippocampus, T₃ in hippocampus) as the immediate (day-1) effects after MPTP treatment. MPTP caused alterations of cellular morphology, RNA:Protein ratio and TPO protein expression, concomitantly depleted TPO mRNA expression and elevated TSH levels in the thyroid gland. Although T₄ levels changed differentially, T₃ levels remained unaltered in thyroid gland throughout the post-treatment days. Results have been discussed mentioning the putative role of T₄ and TSH in apoptosis and/or proliferation/differentiation of thyrocytes. In blood, T₄ levels remained unchanged while the changes in T₃ and TSH levels did not signify the clinical feature of hypo/hyperthyroidism of animals. In the pituitary, both T₄ and T₃ levels remained elevated where TSH differentially altered (elevated followed by depletion) during post-treatment days. Notably, T₄, T₃ and TSH levels did not alter in hypothalamus except initial (day-1) depletion of the T₄ level. Therefore, the feedback control mechanism of hypothalamo-pituitary-blood-thyroid-axis failed to occur after MPTP treatment. Overall, MPTP altered thyroidal status in the brain and peripheral tissues while both events might occur in isolation as well.

Keywords: Different brain regions; Dopaminergic neurons; Hypothalamo-pituitary-blood-thyroid axis; MPTP; ROS; Thyroidal status.