Severe Lesion in Dopaminergic Neurons in Substantia Nigra Associates with a Decrease in Serum Level of Copper

Copper (Cu) involves in oxidation-reduction reactions, and its aggregation in the brain induces oxidative stress. However, previous studies reported a correlation between Cu plasma level and the risk of Parkinson’s disease (PD). In this study, the association between serum Cu level and dopaminergic neuronal death in substantia nigra was assessed in a 6- hydroxydopamine animal model of PD.

The 6-OHDA was injected into the medial forebrain bundle of rats by stereotaxic surgery. Behavioral tests were carried out in the second, fourth, and eighth weeks after the toxin injection to assess the severity of PD. Bloodletting was performed in the eighth week after the toxin injection. Then, dopaminergic neuron death in substantia nigra was evaluated by immunohistochemistry. Copper content was determined by atomic absorption spectrophotometry.

The severity of behavioral symptoms increased gradually after the toxin injection. However, there was no significant difference in serum copper levels among the experimental groups. According to the severity of behavioral symptoms, 6-OHDAtreated rats were divided into two subgroups symptomatic and asymptomatic. DAergic cell survival in symptomatic and asymptomatic subgroups was 83±16 and 45±10 %, respectively, which was lower than that in the control group. The serum copper level in the symptomatic subgroup was significantly lower than in the asymptomatic and solvent groups.

In conclusion, the decrease in serum copper level leads to intensive dopaminergic neuronal death in the substantia nigra.