Matsuura K, Kabuto H, Makino H, Ogawa N
Department of Neuroscience, Okayama University Medical School, Japan.
Brain Res. 1996 Sep 9;733(1):101-4. doi: 10.1016/0006-8993(96)00686-5.
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.
为了揭示帕金森病（PD）的新治疗策略，我们研究了免疫抑制剂环孢素A（CsA）对6-羟基多巴胺（6-OHDA）诱导的小鼠黑质纹状体多巴胺能神经元损伤的保护作用。在诱导6-OHDA损伤7天后，纹状体中的多巴胺（DA）和高香草酸（HVA）分别减少了60%和50%，重复高剂量CsA（20mg/kg）治疗可显著防止这些减少。黑质中的HVA和二羟基苯乙酸（DOPAC）减少了40%，CsA显著增加了6-OHDA损伤小鼠的HVA和DOPAC。此外，CsA增加了黑质中[DOPAC + HVA]/DA的比值，表明在6-OHDA损伤的小鼠中，CsA刺激了DA代谢。这些结果表明，CsA有助于减少6-OHDA诱导的黑质纹状体DA能神经元损伤，提示免疫抑制剂在PD治疗中的潜力。
