Cyclosporin A attenuates degeneration of dopaminergic neurons induced by 6-hydroxydopamine in the mouse brain.

To reveal new therapeutic strategies for Parkinson's disease (PD), we investigated the protective effect of an immunosuppressant, cyclosporin A (CsA), against 6-hydroxydopamine (6-OHDA)-induced injury of nigrostriatal dopamine neurons in mice. Seven days after induction of 6-OHDA lesion, dopamine (DA) and homovanillic acid (HVA) in the striatum were depleted by 60 and 50%, respectively, and repeated high dose CsA (20 mg/kg) treatment significantly protected against these depletions. HVA and dihydroxyphenylacetic acid (DOPAC) in the substantia nigra were depleted by 40%, and CsA significantly increased HVA and DOPAC in 6-OHDA-lesioned mice. Furthermore, CsA increased the [DOPAC + HVA]/DA ratio in the substantia nigra, indicating that DA metabolism was stimulated by CsA in 6-OHDA-lesioned mice. These results suggest that CsA is beneficial in reducing 6-OHDA-induced injury of nigrostriatal DA neurons, indicating the therapeutic potential of immunosuppressants in PD.