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[帕金森病的实验模型]

[Experimental models of Parkinson's disease].

作者信息

Féger J, Pessigliore M, François C, Tremblay L, Hirsch E

机构信息

Inserm U 289 Neurologie et Thérapeutique Expérimentale , Hôpital de La Salpêtrière, 47 boulevard de l'Hôpital F 75013 Paris.

出版信息

Ann Pharm Fr. 2002 Jan;60(1):3-21.

Abstract

Parkinson's disease is a neurodegenerative condition who is related to a large loss of nigral dopaminergic neurons leading to a depletion of dopamine in the striatum. Experimental research is required in order to increase our knowledge on the cellular mechanism and functional consequences of this degenerative process. These models allow investigations of new therapeutics in order to improve the treatment of patients or to test new drugs able to protect any remaining dopaminergic neurons. It is relatively easy to obtain animal models of this disease since the target structure and the neuronal population are clearly defined. Two neurotoxic compounds are available for inducing animal models of Parkinson's disease, 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). A new one, rotenone, requires further investigations. Each of the neurotoxic compounds requires a specific protocol which can be used either with rodents or non-human primates. Progressive lesioning, using MPTP on green african monkeys (Cercopithecus aethiops sabaeus) provides the most reliable model of the idiopathic disease.

摘要

帕金森病是一种神经退行性疾病,与黑质多巴胺能神经元大量丧失有关,导致纹状体中多巴胺耗竭。需要进行实验研究,以增加我们对这种退行性过程的细胞机制和功能后果的了解。这些模型有助于研究新的治疗方法,以改善患者的治疗效果或测试能够保护任何剩余多巴胺能神经元的新药。由于目标结构和神经元群体明确,获得这种疾病的动物模型相对容易。有两种神经毒性化合物可用于诱导帕金森病动物模型,即6-羟基多巴胺(6-OHDA)和1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)。一种新的化合物鱼藤酮,还需要进一步研究。每种神经毒性化合物都需要特定的方案,该方案可用于啮齿动物或非人类灵长类动物。在绿色非洲猴(Cercopithecus aethiops sabaeus)上使用MPTP进行渐进性损伤,可提供最可靠的特发性疾病模型。

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