Meinel J, Radad K, Rausch W-D, Reichmann H, Gille G
Ass. Prof. Gabriele Gille, Department of Neurology, Technical University, Fetscherstr. 74, 01307 Dresden, Germany, e-mail:
Folia Neuropathol. 2015;53(1):29-40. doi: 10.5114/fn.2015.49972.
In the present study, primary mesencephalic cell cultures prepared from embryonic mouse mesencephala were used to investigate the neuroprotective effect of cabergoline, an ergoline D2 receptor agonist, against the pesticide and neurotoxin rotenone relevant to Parkinson disease (PD). Treatment of cultures with cabergoline alone significantly increased the number of tyrosine hydroxylase immunoreactive (THir) neurons and reduced the release of lactate dehydrogenase (LDH) into the culture medium compared to untreated controls. Against rotenone toxicity, cabergoline significantly rescued degenerating THir neurons, reduced the release of LDH into the culture medium and improved the morphology of surviving THir neurons. The neuroprotective effects afforded by cabergoline were independent of dopaminergic stimulation as blocking of dopamine receptors by the dopamine receptor antagonist sulpiride did not prevent them. Furthermore, rotenone-induced formation of reactive oxygen species (ROS) was significantly reduced by cabergoline. Although cabergoline increased the glutathione (GSH) content in the culture, the protective effect for dopaminergic neurons seemed not to be predominantly mediated by increasing GSH, as depletion of GSH by L-buthionine-(S,R)-sulfoximine (BSO), a GSH biosynthesis inhibitor, did not prevent cabergoline-mediated neuroprotection of THir neurons in rotenone-treated cultures. Moreover, cabergoline significantly increased the ATP/protein ratio in primary mesencephalic cell cultures when added alone or prior to rotenone treatment. These results indicate a neuroprotective effect of cabergoline for dopaminergic neurons against rotenone toxicity. This effect was independent of dopamine receptor stimulation and was at least partially mediated by reducing ROS production and increasing the ATP/protein ratio.
在本研究中，使用从胚胎小鼠中脑制备的原代中脑细胞培养物来研究麦角林D2受体激动剂卡麦角林对与帕金森病（PD）相关的农药和神经毒素鱼藤酮的神经保护作用。与未处理的对照相比，单独用卡麦角林处理培养物可显著增加酪氨酸羟化酶免疫反应性（THir）神经元的数量，并减少乳酸脱氢酶（LDH）释放到培养基中。针对鱼藤酮毒性，卡麦角林可显著挽救退化的THir神经元，减少LDH释放到培养基中，并改善存活的THir神经元的形态。卡麦角林提供的神经保护作用与多巴胺能刺激无关，因为多巴胺受体拮抗剂舒必利阻断多巴胺受体并不能阻止这些作用。此外，卡麦角林可显著减少鱼藤酮诱导的活性氧（ROS）形成。虽然卡麦角林增加了培养物中的谷胱甘肽（GSH）含量，但对多巴胺能神经元的保护作用似乎并非主要通过增加GSH介导，因为GSH生物合成抑制剂L-丁硫氨酸-（S，R）-亚砜胺（BSO）耗尽GSH并不能阻止卡麦角林对鱼藤酮处理的培养物中THir神经元的神经保护作用。此外，单独添加卡麦角林或在鱼藤酮处理之前添加时，卡麦角林可显著提高原代中脑细胞培养物中的ATP/蛋白质比率。这些结果表明卡麦角林对多巴胺能神经元具有抗鱼藤酮毒性的神经保护作用。这种作用与多巴胺受体刺激无关，至少部分是通过减少ROS产生和增加ATP/蛋白质比率介导的。
