Iravani Mahmoud M, Haddon Claire O, Cooper J Mark, Jenner Peter, Schapira Anthony H
Neurodegenerative Disease Research Centre, GKT School of Biomedical Sciences, King's College, London, UK.
J Neurochem. 2006 Mar;96(5):1315-21. doi: 10.1111/j.1471-4159.2005.03625.x. Epub 2006 Feb 8.
The neurotoxin MPTP induces nigral dopaminergic cell death in primates and produces a partial model of Parkinson's disease (PD). Pramipexole is a D2/D3 dopamine receptor agonist used in the symptomatic treatment of PD, and which also protects neuronal cells against dopaminergic toxins in vitro. We now demonstrate that pramipexole partially prevents MPTP toxicity in vivo in a primate species. Common marmosets were repeatedly treated with pramipexole either before, coincidentally with, or after low-dose MPTP treatment designed to induce a partial lesion of the substantia nigra. Animals pretreated with pramipexole had a significantly greater number of surviving tyrosine hydroxylase (TH) positive neurones in the pars compacta of the substantia nigra. Pramipexole pretreatment also prevented degeneration of striatal dopamine terminals. Treatment with pramipexole concurrently with MPTP or following MPTP did not prevent TH-positive cell loss. Pramipexole pretreatment appears to induce adaptive changes that protect against dopaminergic cell loss in primates.
神经毒素1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）可诱导灵长类动物黑质多巴胺能细胞死亡，并产生帕金森病（PD）的部分模型。普拉克索是一种D2/D3多巴胺受体激动剂，用于PD的对症治疗，并且在体外也能保护神经元细胞免受多巴胺能毒素的侵害。我们现在证明，普拉克索在灵长类动物体内可部分预防MPTP的毒性。普通狨猴在接受旨在诱导黑质部分损伤的低剂量MPTP治疗之前、同时或之后，反复接受普拉克索治疗。用普拉克索预处理的动物黑质致密部中存活的酪氨酸羟化酶（TH）阳性神经元数量明显更多。普拉克索预处理还可防止纹状体多巴胺终末的退化。在MPTP治疗的同时或之后使用普拉克索治疗并不能防止TH阳性细胞的丢失。普拉克索预处理似乎可诱导适应性变化，从而保护灵长类动物免受多巴胺能细胞丢失的影响。
