Copper (Cu~(2+)) induces degeneration of dopaminergic neurons in the nigrostriatal system of rats

Objective To study the effects of intranigral injection of different doses of CuSO4·5H2O on dopaminergic neuron in the nigrostriatal system of rats. Methods Wistar rats were divided into four groups, including control group, 10 nmol, 50 nmol and 200 nmol copper injected into left substantia nigra (SN) groups. Seven days after the intranigral injection of copper, dopamine (DA) contents in the striatum (Str) were measured by high performance lipid chromotophotography (HPLC); the density of tyrosine hydroxylase (TH) positive axons in the Str was measured by TH staining method; TH and Caspase-3 mRNA expression in the SN were measured by semi-quantitative RT-PCR. We detected the activity of superoxide dismutase (SOD) in the lesioned midbrain of rats using biochemical methods. Results DA and its metabolites contents had no significant difference between control group and low dose (10 nmol) copper group. But from 50 nmol copper group, DA contents in the lesioned sides were reduced with the increase in the copper doses injected, showing a significant linear correlation (F = 34.16, P 0.01). In the 50 nmol copper group, TH positive axons in the Str decreased compared with those of the control and unlesioned sides (F = 121.9, P 0.01). In the 50 nmol copper group, TH mRNA expression decreased (t =3.12, P 0.01) while Caspase-3 mRNA expression increased (t =8.96, P 0.01) in the SN compared with the control. SOD activity decreased in the midbrain of rats treated with 50 nmol copper compared with that of the control (t = 2.33, P0.01). Conclusion Copper could induce damage of dopaminergic neurons in the SN of rats through destroying antioxidant defenses and promoting apoptosis.