Magic™ Anti-TH (Phospho S8) polyclonal antibody

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 (T-4 and T-3) 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 (T-4 in SN and hippocampus, T-3 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 T-4 levels changed differentially, T-3 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, T-4 levels remained unchanged while the changes in T-3 and TSH levels did not signify the clinical feature of hypo/hyperthyroidism of animals. In the pituitary, both T-4 and T-3 levels remained elevated where TSH differentially altered (elevated followed by depletion) during post-treatment days. Notably, T-4, T-3 and TSH levels did not alter in hypothalamus except initial (day-1) depletion of the T-4 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.

Meso-diencephalic dopaminergic neurons are known to modulate locomotor behaviors through their ascending projections to the basal ganglia, which in turn project to the mesencephalic locomotor region, known to control locomotion in vertebrates. In addition to their ascending projections, dopaminergic neurons were found to increase locomotor movements through direct descending projections to the mesencephalic locomotor region and spinal cord. Intriguingly, fibers expressing tyrosine hydroxylase (TH), the ratelimiting enzyme of dopamine synthesis, were also observed around reticulospinal neurons of lampreys. We now examined the origin and the role of this innervation. Using immunofluorescence and tracing experiments, we found that fibers positive for dopamine innervate reticulospinal neurons in the four reticular nudei of lampreys. We identified the dopaminergic source using tracer injections in reticular nuclei, which retrogradely labeled dopaminergic neurons in a caudal diencephalic nucleus (posterior tuberculum WTI). Using voltammetry in brain preparations isolated in vitro, we found that PT stimulation evoked dopamine release in all four reticular nuclei, but not in the spinal cord. In semi-intact preparations where the brain is accessible and the body moves, PT stimulation evoked swimming, and injection of a D-1 receptor antagonist within the middle rhombencephalic reticular nucleus was sufficient to decrease reticulospinal activity and PT-evoked swimming. Our study reveals that dopaminergic neurons have access to command neurons that integrate sensory and descending inputs to activate spinal locomotor neurons. As such, our findings strengthen the idea that dopamine can modulate locomotor behavior both via ascending projections to the basal ganglia and through descending projections to brainstem motor circuits.