Dopaminergic Neuronal Death in Substantia Nigra Associates with Serum Levels of Total Bilirubin, Selenium, and Zinc: Evidences from 6-Hydroxydopamine Animal Model of Parkinson's Disease.

Mild to moderate dopaminergic (DA) neuronal death in substantia nigra pars compacta (SNc) as the main pathological hallmark of Parkinson's disease (PD) is usually silent and does not produce marked clinical symptoms. In this study, we investigated the association between SNc DA neuronal loss and serum levels of total bilirubin (TB), selenium (Se), and zinc (Zn) in 6-hydroxydopamine (6-OHDA) animal model of PD. The neurotoxin of 6-OHDA was injected into the medial forebrain bundle of right hemisphere by stereotaxic surgery. Two conventional behavioral tests were carried out in several steps after the toxin to confirm the model reproduction and quantify severity and progress of 6-OHDA-induced PD. Blood samples were collected within 1 week before the toxin and in the second, fifth, and eighth weeks thereafter. Immunohistochemistry (IHC) assessments were performed on the rat's brain to determine the severity of DA neuronal loss in SNc. The severity of behavioral symptoms and TB levels were progressively increased in 6-OHDA-treated rats. On the other hand, Se and Zn levels in them were lower than control. These changes were observed in rats with severe or mild behavioral symptoms. Also, IHC revealed that changes in TB, Se, and Zn associate with SNc DA neuronal loss but do not correlate with its severity. Significant changes in serum levels of TB, Se, and Zn in the mild SNc DA neuronal loss suggest them as valuable parameters for establishment of a serum profile for early detection of PD.